Plasmodium vivax is the predominant species causing malaria in the Americas and Asia-Pacific regions (WHO, 2014). Due to its unique biology, P. vivax is less susceptible to commonly-used vector control measures (Mueller et al., 2009). With renewed funding and commitment towards the goal of eliminating malaria, the development and deployment of an effective vaccine against P. vivax has become a high priority (malERA Consultative Group on Vaccines, 2011).

The epidemiology of P. vivax provides strong indication that the development of an effective vaccine is feasible. Clinical immunity to P. vivax is acquired more rapidly than to P. falciparum and, in moderate and highly endemic areas, clinical disease is virtually absent in children older than five years (Phimpraphi et al., 2008; Lin et al., 2010; Robinson et al., 2015). Sub-microscopic infections are common even in areas where malaria transmission has been substantially reduced (Cheng et al., 2015; Bousema et al., 2014), suggesting the development of effective immunity that provides good control of parasitemia. Whilst our understanding of the protective immune effector mechanisms is incomplete, the humoral component is thought to be essential for the development of anti-P. vivax immunity, and antibodies confer protection by both preventing high-density parasitemia and inhibiting blood-stage replication (Longley et al., 2016). Evidence of relatively long-lived IgG levels and/or seropositivity to P. vivax proteins such as circumsporozoite protein (CSP), merozoite surface protein 1 (MSP1), apical membrane antigen 1 (AMA1) and Duffy binding protein (DBP) have been reported even in the absence of detectable P. vivax infections (Longley et al., 2015; Wipasa et al., 2010; Achtman et al., 2005).

A highly-efficacious malaria vaccine has unfortunately not yet been achieved for any of the Plasmodium spp. parasites, and the vast majority of vaccines in development are based on single recombinant protein antigens (Halbroth and Draper, 2015). For P. falciparum, more than 15 antigens are under pre-clinical or clinical testing, including the pre-erythrocytic, CSP-based RTS,S/AS01 vaccine, which has recently completed Phase 3 trials (Agnandji et al., 2012; RTS,S Clinical Trials Partnership, 2014). In contrast, for P. vivax only a handful of proteins have been studied, with the blood-stage DBP, MSP1, and transmission-blocking protein Pvs25 as the main vaccine candidates (Halbroth and Draper, 2015; Mueller et al., 2015). The moderate success of the P. falciparum RTS,S vaccine has also made P. vivax CSP a main vaccine candidate (Mueller et al., 2015; Salman et al., 2017; Bennett et al., 2016). The potential of novel, pre-erythrocytic candidate antigens, including P. vivax cell-traversal protein for ookinetes (CelTOS) and thrombospondin-related anonymous protein (TRAP) is being investigated in animal models (Mueller et al., 2015; Alves et al., 2017; Bauza et al., 2014).

Recent serological screens of large panels of P. falciparum proteins in naturally-exposed populations have identified several antigenic targets associated with protective immunity, and strongly support the hypothesis that a multicomponent vaccine possibly including antigens from different stages of the parasites life cycle would offer a higher degree of protection than a single component vaccine (Halbroth and Draper, 2015; Richards et al., 2013; Osier et al., 2014a). For P. vivax, the availability of the genome sequence (Carlton et al., 2008) and transcriptome (Bozdech et al., 2008) have enhanced our understanding of the parasite’s biology, facilitating the identification of many proteins that are homologous to P. falciparum antigens (Chen et al., 2010; Lu et al., 2014; Finney et al., 2014). Given the lack of methods to continuously culture P. vivax to study specific proteins in vitro, or animal models for extensive in vivo assays, the study of targets of human natural immunity in exposed populations must play an essential role in identifying and prioritizing P. vivax antigens for further functional characterization for vaccine or biomarker development (Chia et al., 2014). To date, however, the number, identity, and relative importance of P. vivax antigenic targets remains poorly explored (Cutts et al., 2014). Antibodies to proteins such as MSP3α, MSP9 (30) and DBP (King et al., 2008; Cole-Tobian et al., 2009) have shown strong associations with reduced risk of clinical disease or blood-stage infection. Screening studies to extend the pool of P. vivax vaccine candidates remain scarce (Cutts et al., 2014).

To explore the reservoir of antigenic targets and prioritize candidates for functional characterization, we investigated the association between IgG to a comprehensive library of 38 P. vivax recombinant antigens and risk of vivax malaria in a cohort of young Papua New Guinean (PNG) children with well-characterized differences in exposure to P. vivax infections (Lin et al., 2010). To our knowledge, the potential existence of synergistic or additive effects of combinations of antibody responses to a large panel of P. vivax antigens has never been explored. We applied a novel simulated annealing algorithm to efficiently explore the vast space of antigen combinations and thus identify combinations with optimal potential protective efficacy (PPE). High antibody levels to multiple antigens, including several novel proteins were strongly associated with reduced risk of vivax malaria, independently of individual differences in exposure, age, and transmission season. Combinations of antigens were identified with a PPE of >90%. These data identify several antigens that should be prioritized for further functional characterization. The naturally-acquired anti-malarial immunity explored in this study supports the development of a highly-efficacious, multicomponent P. vivax vaccine.

The development and deployment of an effective P. vivax vaccine has become a priority for accelerating malaria elimination in the Asia-Pacific and the Americas (Tanner et al., 2015). To date, however, remarkably few P. vivax vaccine candidates are close to or have reached clinical trials (Mueller et al., 2015). To expand and prioritize the reservoir of antigenic targets for further functional characterization for use in vaccine or biomarker development, we measured total IgG antibody levels to 38 P. vivax recombinant proteins, investigating their relationship with prospective risk of vivax malaria in a longitudinal cohort of PNG children aged 1–3 years. For the first time, the potential protective efficacy of combination of antigens, and the thresholds necessary for an association with protection were investigated.

Although the young children included in the present study are actively acquiring clinical immunity, as indicated by a highly-significant decrease in incidence of clinical P. vivax episodes (Lin et al., 2010), most still had relatively low antibody responses, with more than 10% of children exceeding 10% of adult levels to only 22 proteins. Antibodies to almost all proteins were boosted by concurrent P. vivax infections (n = 30), and 29 increased with age and/or lifetime exposure, indicating the antibody levels are both a marker of concurrent and past exposure to P. vivax. Despite these generally low IgG antibody levels, high levels to 31 of 38 proteins (81.6%) were significantly associated with protection, indicating that these antibody levels have started to exceed the threshold above which antibody levels are biomarkers of protection rather than exposure (Stanisic et al., 2015).

Antibody levels were often moderately or even highly correlated between antigens, and not only to different regions of the same antigen, such as MSP3α (rho = 0.52–0.93), or to different alleles of the same antigen such as PvDBP (rho = 0.76–0.995). In particular, antibodies to the WGCF-expressed, highly-immunogenic proteins showed very high correlations (rho = 0.61–0.95). Without further functional investigation, it is difficult to determine if these correlations indicate co-acquisition or cross-reactivity, or whether cross-reactive antibodies are functional or merely recognize different proteins.

The high correlations of antibody levels to different DBP alleles were expected, as some are very similar in sequence (e.g. the variants AH and C differ only at amino acid residue 371), thus antibody responses are likely to be highly cross-reactive between variants. However, despite 50% identity, correlations between antibodies to the different alleles of DBPII and EBP were only moderate (rho = 0.36–0.48, p<0.001) and not higher than those with other merozoite surface proteins, indicating only a limited potential for cross-reactive antibodies between these proteins. For the RBP proteins included in this study, we have previously showed that polyclonal antibodies raised in rabbits recognize the homologous but not heterologous proteins (França et al., 2016b). The correlated responses are therefore likely due to co-acquisition, and the combination of several RBPs may have synergistic or additive effects (França et al., 2016b). For DBPII, although this and previous studies observed the presence of strain-specific antibodies (Cole-Tobian et al., 2009), strain-transcending antibodies (in particular those targeting the binding pocket) have been described (King et al., 2008; Chen et al., 2016; Wongkidakarn et al., 2016), indicating that a DBPII vaccine targeting these strain-transcending epitopes may be able to overcome the large genetic diversity of DBPII. Nevertheless, the analyses of antigen combinations clearly indicated that combining DBPII with other antigens such as one of several RBPs is likely to be beneficial.

The majority of the antigens associated with protection against vivax malaria in this cohort were newly described or understudied, such as EBP, P41, CyRPA, RBP1a, and RBP2b. Many of these proteins were similarly or more strongly associated with protective immunity than antibodies to well-studied vaccine candidate antigens such as MSP3α, AMA1, MSP1, and CSP (Bennett et al., 2016; Cutts et al., 2014; Stanisic et al., 2013), clearly demonstrating that the repertoire of possible antigenic targets present in the P. vivax genome should be further expanded. Interestingly, among the highly-immunogenic proteins expressed in the WGCF system, only two, PVX_122805, a conserved hypothetical protein and PVX_088820, a member of the Pv-fam-a tryptophan-rich antigen family showed substantial association with protection individually, and were regularly included in combinations of 5–15 antigens. This indicates that immunogenicity by itself is a relatively poor predictor of association with protection, and while such proteins may be good markers of exposure, it is less clear whether they would make effective vaccine candidate antigens.

There was a clear hierarchy in the order in which antigens were included into the best antigen-combinations. The top protective antigens were consistently at the top end of all possible random five-way combinations, an observation that is unlikely to be due to chance if all antigens were equally protective when in combinations. The best single antigen EBP followed by PVX_081550 were always present among the most frequently included proteins in higher combinations. Additional proteins common in combinations of three were CyRPA, RBP1a and RBP2b. Apart from RBP2b, these same proteins are also commonly found in four and five antigen-combinations, together with DBPII, P41 and PVX_099930 (RhopH2).

Literature on the little-studied P. vivax antigens associated with protection here is at best scarce. We have recently determined that RBP2b binds exclusively to reticulocytes, raising the prospect that RBP2b may be involved in P. vivax reticulocyte-specificity (França et al., 2016b). Among the other antigens strongly associated with protection, P41 is a GPI-anchored protein localized on the merozoite surface which forms a heterodimer with P12 (Hostetler et al., 2015). In P. falciparum, neither P41 nor P12 homologs are essential for in vitro parasite growth (Tonkin et al., 2013), but both are immunogenic, and antibodies have been associated with clinical protection (Richards et al., 2013; Osier et al., 2014a). The P. falciparum homolog of PVX_081550 has recently been identified as StAR-related lipid transfer protein localized on the parasitophorous vacuole (van Ooij et al., 2013). Both the P. falciparum homolog and P. vivax PVX_081550 proteins are immunogenic (Fan et al., 2013). It is, however, unclear whether antibodies to PVX_081550 interfere with parasite function or are simply elicited by proteins released from the parasitophorous vacuole upon schizont rupture and thus serve as markers of an individual’s immune status (França et al., 2016a). Lastly, also in P. falciparum, CyRPA forms a complex with PfRh5 and PfRipr on the merozoite surface. This complex is involved in binding basigin on the erythrocyte surface (Reddy et al., 2015). P. falciparum CyRPA seems to not be under immune selection pressure and is highly-conserved, with only a single polymorphism detected across 18 P. falciparum strains (Beeson et al., 2016). Antibodies raised against P. falciparum CyRPA were nevertheless capable of inhibiting merozoite invasion (Beeson et al., 2016), block binding of CyRPA to Rh5 and Rh5/CyRPA/Ripr complex formation (Chen et al., 2017), and both in vitro and in vivo parasite growth inhibitory activity, more stronger when in combination with PfRh5 (Favuzza et al., 2017). The P. vivax CyRPA seems to be highly-reactogenic (França et al., 2016a), suggesting that their function, or at least exposure to the immune system, may differ between the two species.

IgG subclass responses to some P. vivax antigens such as RBP1a, DBPII, MSP1 19, and CSP (França et al., 2016b; Tran et al., 2005; Maestre et al., 2010; Yildiz Zeyrek et al., 2011; Zeyrek et al., 2008), as well as several different P. falciparum antigens (Stanisic et al., 2015; Ahmed Ismail et al., 2014; Richards et al., 2010; Reiling et al., 2010; Noland et al., 2015; Tongren et al., 2006) have consistently shown that the presence of IgG1 and/or IgG3 in variable ratios is likely to play a role in protection against infection and/or clinical disease. The role of IgG2 and IgG4 antibodies however, remains mostly unclear. IgG2 antibodies have been correlated with lower P. falciparum parasitemia (Ahmed Ismail et al., 2014) and risk of infection (Aucan et al., 2000), while IgG4 levels were associated with an enhanced risk of infection and disease (Aucan et al., 2000). Neither showed significant ability to promote opsonic phagocytosis (Osier et al., 2014b), with IgG4 possibly inhibiting this process (Chaudhury et al., 2017). We have previously measured IgG subclass 1, 2, 3 and 4 responses to the 5 RBPs included in this study, showing that IgG1 and IgG3 are the predominant subclasses in this cohort of PNG children (França et al., 2016b). IgG1 to RBP1a and RBP2b showed the strongest association with protection in multivariate models. Interestingly, adults showed substantially higher levels of IgG3 for all antigens (IgG3 being predominant for RBP1a), and substantial levels of IgG2 for some (e.g. RBP2b) but not all antigens. Children showed some early evidence of switching to IgG3 for RBP1a and RBP2-P2 with maturation of immune responses, and increase in age and exposure to malaria parasites (França et al., 2016b).

Little is known about the threshold necessary for antibody levels to switch from being biomarkers of exposure to biomarkers of protection (Stanisic et al., 2015). Large variation in the threshold levels associated with 50% reduction in vivax malaria risk was observed for the present antigen panel. Although this type of analysis cannot differentiate between direct, causal protective effect of antibodies and a statistical association, the observations that many of the antigens most consistently associated with protection in multi-antigen combinations (e.g. PVX_081550, EBP, CyRPA) show both relatively low immunogenicity and low 50% protection threshold levels suggests that for some of the most promising candidate antigens, low antibody levels may be sufficient for protection. It is possible that critical antigens or epitopes have to be weakly immunogenic to avoid acquisition of host immunity. Antigens with little reactivity and associated with acquired immunity at low antibody levels might thus be the most promising for vaccine development. It was, however, not possible to determine in this study whether antibodies to these proteins have better avidity/affinity than some antigens that induce very high antibody levels. One limitation of the dose-response model used in this study is that it only includes one antigen at a time, and thus doesn’t account for the complexity of highly-correlated antibody responses.

We focused on 1–3 years old children as early infancy is a critical time in the development of immunity to malaria (Longley et al., 2016). Nevertheless, further studies including older age groups from different transmission settings will be required to confirm the detected hierarchy in antibody responses and their association with protection. To our knowledge, the present study is the largest comprehensive panel of P. vivax antigens measured in a well-designed cohort study for identification of associations with malaria risk, and the first one to investigate both the effect of multiple combinations and the threshold antibody levels necessary for protection. Our results identify important targets of naturally-acquired immunity that may contribute to clinical protection and should thus be prioritized for functional studies. These results clearly indicate that examining multiple antigens simultaneously can best correlate with protection, as it might optimally define the breadth of the immune response required for clinical immunity. Taken together, our results suggest that a well-designed, multicomponent P. vivax vaccine may be more efficacious than single-component vaccines.

Future research should focus on uncovering the functional role of the unknown and understudied proteins identified in this study, and their potential for vaccines, biomarkers of immunity, or both. The measurement of functionality, e.g. antibodies’ capacity to promote opsonic phagocytosis or ability to block binding/invasion to red blood cells will be particularly important (Teo et al., 2016). Although it remains unclear which mechanisms are most important for protection from malaria infection or clinical disease, recent studies with P. falciparum suggest that a combination of functional mechanisms may be important for protective immunity (Osier et al., 2014b; Hill et al., 2013; Hill et al., 2016; Chiu et al., 2015; Joos et al., 2010; Murungi et al., 2016). Hence, the presence/levels of functional antibodies might possibly be even better correlates of protective immunity than total IgG antibody levels.

1. 1. Achtman AH
   2. Bull PC
   3. Stephens R
   4. Langhorne J

   (2005) Longevity of the immune response and memory to blood-stage malaria infection

   Current Topics in Microbiology and Immunology 297:71–102.

   https://doi.org/10.1007/3-540-29967-X_3

   • PubMed
   • Google Scholar
2. 1. Agnandji ST
   2. Lell B
   3. Fernandes JF
   4. Abossolo BP
   5. Methogo BG
   6. Kabwende AL
   7. Adegnika AA
   8. Mordmüller B
   9. Issifou S
   10. Kremsner PG
   11. Sacarlal J
   12. Aide P
   13. Lanaspa M
   14. Aponte JJ
   15. Machevo S
   16. Acacio S
   17. Bulo H
   18. Sigauque B
   19. Macete E
   20. Alonso P
   21. Abdulla S
   22. Salim N
   23. Minja R
   24. Mpina M
   25. Ahmed S
   26. Ali AM
   27. Mtoro AT
   28. Hamad AS
   29. Mutani P
   30. Tanner M
   31. Tinto H
   32. D'Alessandro U
   33. Sorgho H
   34. Valea I
   35. Bihoun B
   36. Guiraud I
   37. Kaboré B
   38. Sombié O
   39. Guiguemdé RT
   40. Ouédraogo JB
   41. Hamel MJ
   42. Kariuki S
   43. Oneko M
   44. Odero C
   45. Otieno K
   46. Awino N
   47. McMorrow M
   48. Muturi-Kioi V
   49. Laserson KF
   50. Slutsker L
   51. Otieno W
   52. Otieno L
   53. Otsyula N
   54. Gondi S
   55. Otieno A
   56. Owira V
   57. Oguk E
   58. Odongo G
   59. Woods JB
   60. Ogutu B
   61. Njuguna P
   62. Chilengi R
   63. Akoo P
   64. Kerubo C
   65. Maingi C
   66. Lang T
   67. Olotu A
   68. Bejon P
   69. Marsh K
   70. Mwambingu G
   71. Owusu-Agyei S
   72. Asante KP
   73. Osei-Kwakye K
   74. Boahen O
   75. Dosoo D
   76. Asante I
   77. Adjei G
   78. Kwara E
   79. Chandramohan D
   80. Greenwood B
   81. Lusingu J
   82. Gesase S
   83. Malabeja A
   84. Abdul O
   85. Mahende C
   86. Liheluka E
   87. Malle L
   88. Lemnge M
   89. Theander TG
   90. Drakeley C
   91. Ansong D
   92. Agbenyega T
   93. Adjei S
   94. Boateng HO
   95. Rettig T
   96. Bawa J
   97. Sylverken J
   98. Sambian D
   99. Sarfo A
   100. Agyekum A
   101. Martinson F
   102. Hoffman I
   103. Mvalo T
   104. Kamthunzi P
   105. Nkomo R
   106. Tembo T
   107. Tegha G
   108. Tsidya M
   109. Kilembe J
   110. Chawinga C
   111. Ballou WR
   112. Cohen J
   113. Guerra Y
   114. Jongert E
   115. Lapierre D
   116. Leach A
   117. Lievens M
   118. Ofori-Anyinam O
   119. Olivier A
   120. Vekemans J
   121. Carter T
   122. Kaslow D
   123. Leboulleux D
   124. Loucq C
   125. Radford A
   126. Savarese B
   127. Schellenberg D
   128. Sillman M
   129. Vansadia P
   130. RTS,S Clinical Trials Partnership

   (2012) A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants

   The New England journal of medicine 367:2284–2295.

   https://doi.org/10.1056/NEJMoa1208394

   • PubMed
   • Google Scholar
3. 1. Ahmed Ismail H
   2. Tijani MK
   3. Langer C
   4. Reiling L
   5. White MT
   6. Beeson JG
   7. Wahlgren M
   8. Nwuba R
   9. Persson KE

   (2014) Subclass responses and their half-lives for antibodies against EBA175 and PfRh2 in naturally acquired immunity against Plasmodium falciparum malaria

   Malaria Journal 13:425.

   https://doi.org/10.1186/1475-2875-13-425

   • PubMed
   • Google Scholar
4. 1. Alves E
   2. Salman AM
   3. Leoratti F
   4. Lopez-Camacho C
   5. Viveros-Sandoval ME
   6. Lall A
   7. El-Turabi A
   8. Bachmann MF
   9. Hill AV
   10. Janse CJ
   11. Khan SM
   12. Reyes-Sandoval A

   (2017) Evaluation of plasmodium vivax cell-traversal protein for ookinetes and sporozoites as a preerythrocytic P. vivax vaccine

   Clinical and Vaccine Immunology 24:e00501-16.

   https://doi.org/10.1128/CVI.00501-16

   • PubMed
   • Google Scholar
5. 1. Arumugam TU
   2. Ito D
   3. Takashima E
   4. Tachibana M
   5. Ishino T
   6. Torii M
   7. Tsuboi T

   (2014) Application of wheat germ cell-free protein expression system for novel malaria vaccine candidate discovery

   Expert Review of Vaccines 13:75–85.

   https://doi.org/10.1586/14760584.2014.861747

   • PubMed
   • Google Scholar
6. 1. Aucan C
   2. Traoré Y
   3. Tall F
   4. Nacro B
   5. Traoré-Leroux T
   6. Fumoux F
   7. Rihet P

   (2000) High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria

   Infection and Immunity 68:1252–1258.

   https://doi.org/10.1128/IAI.68.3.1252-1258.2000

   • PubMed
   • Google Scholar
7. 1. Bauza K
   2. Malinauskas T
   3. Pfander C
   4. Anar B
   5. Jones EY
   6. Billker O
   7. Hill AV
   8. Reyes-Sandoval A

   (2014) Efficacy of a Plasmodium vivax malaria vaccine using ChAd63 and modified vaccinia Ankara expressing thrombospondin-related anonymous protein as assessed with transgenic Plasmodium berghei parasites

   Infection and Immunity 82:1277–1286.

   https://doi.org/10.1128/IAI.01187-13

   • PubMed
   • Google Scholar
8. 1. Beeson JG
   2. Drew DR
   3. Boyle MJ
   4. Feng G
   5. Fowkes FJ
   6. Richards JS

   (2016) Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

   FEMS Microbiology Reviews 40:343–372.

   https://doi.org/10.1093/femsre/fuw001

   • PubMed
   • Google Scholar
9. 1. Bennett JW
   2. Yadava A
   3. Tosh D
   4. Sattabongkot J
   5. Komisar J
   6. Ware LA
   7. McCarthy WF
   8. Cowden JJ
   9. Regules J
   10. Spring MD
   11. Paolino K
   12. Hartzell JD
   13. Cummings JF
   14. Richie TL
   15. Lumsden J
   16. Kamau E
   17. Murphy J
   18. Lee C
   19. Parekh F
   20. Birkett A
   21. Cohen J
   22. Ballou WR
   23. Polhemus ME
   24. Vanloubbeeck YF
   25. Vekemans J
   26. Ockenhouse CF

   (2016) Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy

   PLOS Neglected Tropical Diseases 10:e0004423.

   https://doi.org/10.1371/journal.pntd.0004423

   • PubMed
   • Google Scholar
10. 1. Bousema T
    2. Okell L
    3. Felger I
    4. Drakeley C

    (2014) Asymptomatic malaria infections: detectability, transmissibility and public health relevance

    Nature Reviews Microbiology 12:833–840.

    https://doi.org/10.1038/nrmicro3364

    • PubMed
    • Google Scholar
11. 1. Bozdech Z
    2. Mok S
    3. Hu G
    4. Imwong M
    5. Jaidee A
    6. Russell B
    7. Ginsburg H
    8. Nosten F
    9. Day NP
    10. White NJ
    11. Carlton JM
    12. Preiser PR

    (2008) The transcriptome of Plasmodium vivax reveals divergence and diversity of transcriptional regulation in malaria parasites

    PNAS 105:16290–16295.

    https://doi.org/10.1073/pnas.0807404105

    • PubMed
    • Google Scholar
12. 1. Carlton JM
    2. Adams JH
    3. Silva JC
    4. Bidwell SL
    5. Lorenzi H
    6. Caler E
    7. Crabtree J
    8. Angiuoli SV
    9. Merino EF
    10. Amedeo P
    11. Cheng Q
    12. Coulson RM
    13. Crabb BS
    14. Del Portillo HA
    15. Essien K
    16. Feldblyum TV
    17. Fernandez-Becerra C
    18. Gilson PR
    19. Gueye AH
    20. Guo X
    21. Kang'a S
    22. Kooij TW
    23. Korsinczky M
    24. Meyer EV
    25. Nene V
    26. Paulsen I
    27. White O
    28. Ralph SA
    29. Ren Q
    30. Sargeant TJ
    31. Salzberg SL
    32. Stoeckert CJ
    33. Sullivan SA
    34. Yamamoto MM
    35. Hoffman SL
    36. Wortman JR
    37. Gardner MJ
    38. Galinski MR
    39. Barnwell JW
    40. Fraser-Liggett CM

    (2008) Comparative genomics of the neglected human malaria parasite Plasmodium vivax

    Nature 455:757–763.

    https://doi.org/10.1038/nature07327

    • PubMed
    • Google Scholar
13. 1. Chaudhury S
    2. Regules JA
    3. Darko CA
    4. Dutta S
    5. Wallqvist A
    6. Waters NC
    7. Jongert E
    8. Lemiale F
    9. Bergmann-Leitner ES

    (2017) Delayed fractional dose regimen of the RTS,S/AS01 malaria vaccine candidate enhances an IgG4 response that inhibits serum opsonophagocytosis

    Scientific Reports 7:7998.

    https://doi.org/10.1038/s41598-017-08526-5

    • PubMed
    • Google Scholar
14. 1. Chen E
    2. Salinas ND
    3. Huang Y
    4. Ntumngia F
    5. Plasencia MD
    6. Gross ML
    7. Adams JH
    8. Tolia NH

    (2016) Broadly neutralizing epitopes in the Plasmodium vivax vaccine candidate Duffy Binding Protein

    PNAS 113:6277–6282.

    https://doi.org/10.1073/pnas.1600488113

    • PubMed
    • Google Scholar
15. 1. Chen JH
    2. Jung JW
    3. Wang Y
    4. Ha KS
    5. Lu F
    6. Lim CS
    7. Takeo S
    8. Tsuboi T
    9. Han ET

    (2010) Immunoproteomics profiling of blood stage Plasmodium vivax infection by high-throughput screening assays

    Journal of Proteome Research 9:6479–6489.

    https://doi.org/10.1021/pr100705g

    • PubMed
    • Google Scholar
16. 1. Chen L
    2. Xu Y
    3. Wong W
    4. Thompson JK
    5. Healer J
    6. Goddard-Borger ED
    7. Lawrence MC
    8. Cowman AF

    (2017) Structural basis for inhibition of erythrocyte invasion by antibodies to Plasmodium falciparum protein CyRPA

    eLife 6:e21347.

    https://doi.org/10.7554/eLife.21347

    • PubMed
    • Google Scholar
17. 1. Cheng Q
    2. Cunningham J
    3. Gatton ML

    (2015) Systematic review of sub-microscopic P. vivax infections: prevalence and determining factors

    PLoS Neglected Tropical Diseases 9:e3413.

    https://doi.org/10.1371/journal.pntd.0003413

    • PubMed
    • Google Scholar
18. 1. Chia WN
    2. Goh YS
    3. Rénia L

    (2014) Novel approaches to identify protective malaria vaccine candidates

    Frontiers in Microbiology 5:586.

    https://doi.org/10.3389/fmicb.2014.00586

    • PubMed
    • Google Scholar
19. 1. Chiu CY
    2. Hodder AN
    3. Lin CS
    4. Hill DL
    5. Li Wai Suen CS
    6. Schofield L
    7. Siba PM
    8. Mueller I
    9. Cowman AF
    10. Hansen DS

    (2015) Antibodies to the Plasmodium falciparum proteins MSPDBL1 and MSPDBL2 opsonize merozoites, inhibit parasite growth, and predict protection from clinical malaria

    Journal of Infectious Diseases 212:406–415.

    https://doi.org/10.1093/infdis/jiv057

    • PubMed
    • Google Scholar
20. 1. Chiu CY
    2. White MT
    3. Healer J
    4. Thompson JK
    5. Siba PM
    6. Mueller I
    7. Cowman AF
    8. Hansen DS

    (2016) Different regions of Plasmodium falciparum erythrocyte-binding antigen 175 induce antibody responses to infection of varied efficacy

    Journal of Infectious Diseases 214:96–104.

    https://doi.org/10.1093/infdis/jiw119

    • PubMed
    • Google Scholar
21. 1. Cole-Tobian JL
    2. Michon P
    3. Biasor M
    4. Richards JS
    5. Beeson JG
    6. Mueller I
    7. King CL

    (2009) Strain-specific duffy binding protein antibodies correlate with protection against infection with homologous compared to heterologous plasmodium vivax strains in Papua New Guinean children

    Infection and Immunity 77:4009–4017.

    https://doi.org/10.1128/IAI.00158-09

    • PubMed
    • Google Scholar
22. 1. Cutts JC
    2. Powell R
    3. Agius PA
    4. Beeson JG
    5. Simpson JA
    6. Fowkes FJ

    (2014) Immunological markers of Plasmodium vivax exposure and immunity: a systematic review and meta-analysis

    BMC Medicine 12:150.

    https://doi.org/10.1186/s12916-014-0150-1

    • PubMed
    • Google Scholar
23. 1. Dent AE
    2. Malhotra I
    3. Wang X
    4. Babineau D
    5. Yeo KT
    6. Anderson T
    7. Kimmel RJ
    8. Angov E
    9. Lanar DE
    10. Narum D
    11. Dutta S
    12. Richards J
    13. Beeson JG
    14. Crabb BS
    15. Cowman AF
    16. Horii T
    17. Muchiri E
    18. Mungai PL
    19. King CL
    20. Kazura JW

    (2015) Contrasting patterns of serologic and functional antibody dynamics to Plasmodium falciparum antigens in a kenyan birth cohort

    Clinical and Vaccine Immunology 23:104–116.

    https://doi.org/10.1128/CVI.00452-15

    • PubMed
    • Google Scholar
24. 1. Fan YT
    2. Wang Y
    3. Ju C
    4. Zhang T
    5. Xu B
    6. Hu W
    7. Chen JH

    (2013) Systematic analysis of natural antibody responses to P. falciparum merozoite antigens by protein arrays

    Journal of Proteomics 78:148–158.

    https://doi.org/10.1016/j.jprot.2012.11.020

    • PubMed
    • Google Scholar
25. 1. Favuzza P
    2. Guffart E
    3. Tamborrini M
    4. Scherer B
    5. Dreyer AM
    6. Rufer AC
    7. Erny J
    8. Hoernschemeyer J
    9. Thoma R
    10. Schmid G
    11. Gsell B
    12. Lamelas A
    13. Benz J
    14. Joseph C
    15. Matile H
    16. Pluschke G
    17. Rudolph MG

    (2017) Structure of the malaria vaccine candidate antigen CyRPA and its complex with a parasite invasion inhibitory antibody

    eLife 6:e20383.

    https://doi.org/10.7554/eLife.20383

    • PubMed
    • Google Scholar
26. 1. Finney OC
    2. Danziger SA
    3. Molina DM
    4. Vignali M
    5. Takagi A
    6. Ji M
    7. Stanisic DI
    8. Siba PM
    9. Liang X
    10. Aitchison JD
    11. Mueller I
    12. Gardner MJ
    13. Wang R

    (2014) Predicting antidisease immunity using proteome arrays and sera from children naturally exposed to malaria

    Molecular & Cellular Proteomics 13:2646–2660.

    https://doi.org/10.1074/mcp.M113.036632

    • PubMed
    • Google Scholar
27. 1. França CT
    2. He WQ
    3. Gruszczyk J
    4. Lim NT
    5. Lin E
    6. Kiniboro B
    7. Siba PM
    8. Tham WH
    9. Mueller I

    (2016b) Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children

    PLOS Neglected Tropical Diseases 10:e0005014.

    https://doi.org/10.1371/journal.pntd.0005014

    • PubMed
    • Google Scholar
28. 1. França CT
    2. Hostetler JB
    3. Sharma S
    4. White MT
    5. Lin E
    6. Kiniboro B
    7. Waltmann A
    8. Darcy AW
    9. Li Wai Suen CS
    10. Siba P
    11. King CL
    12. Rayner JC
    13. Fairhurst RM
    14. Mueller I

    (2016a) An antibody screen of a Plasmodium vivax antigen library identifies novel merozoite proteins associated with clinical protection

    PLOS Neglected Tropical Diseases 10:e0004639.

    https://doi.org/10.1371/journal.pntd.0004639

    • PubMed
    • Google Scholar
29. 1. Gruszczyk J
    2. Lim NT
    3. Arnott A
    4. He WQ
    5. Nguitragool W
    6. Roobsoong W
    7. Mok YF
    8. Murphy JM
    9. Smith KR
    10. Lee S
    11. Bahlo M
    12. Mueller I
    13. Barry AE
    14. Tham WH

    (2016) Structurally conserved erythrocyte-binding domain in Plasmodium provides a versatile scaffold for alternate receptor engagement

    PNAS 113:E191–E200.

    https://doi.org/10.1073/pnas.1516512113

    • PubMed
    • Google Scholar
30. 1. Halbroth BR
    2. Draper SJ

    (2015) Recent developments in malaria vaccinology

    Advances in parasitology 88:1–49.

    https://doi.org/10.1016/bs.apar.2015.03.001

    • PubMed
    • Google Scholar
31. 1. Hill DL
    2. Eriksson EM
    3. Li Wai Suen CS
    4. Chiu CY
    5. Ryg-Cornejo V
    6. Robinson LJ
    7. Siba PM
    8. Mueller I
    9. Hansen DS
    10. Schofield L

    (2013) Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria

    PLoS One 8:e74627.

    https://doi.org/10.1371/journal.pone.0074627

    • PubMed
    • Google Scholar
32. 1. Hill DL
    2. Wilson DW
    3. Sampaio NG
    4. Eriksson EM
    5. Ryg-Cornejo V
    6. Harrison GL
    7. Uboldi AD
    8. Robinson LJ
    9. Beeson JG
    10. Siba P
    11. Cowman AF
    12. Hansen DS
    13. Mueller I
    14. Schofield L

    (2016) Merozoite Antigens of Plasmodium falciparum Elicit Strain-Transcending Opsonizing Immunity

    Infection and Immunity 84:2175–2184.

    https://doi.org/10.1128/IAI.00145-16

    • PubMed
    • Google Scholar
33. 1. Hostetler JB
    2. Sharma S
    3. Bartholdson SJ
    4. Wright GJ
    5. Fairhurst RM
    6. Rayner JC

    (2015) A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New Vaccine Candidates and Protein-Protein Interactions

    PLOS Neglected Tropical Diseases 9:e0004264.

    https://doi.org/10.1371/journal.pntd.0004264

    • PubMed
    • Google Scholar
34. 1. Joos C
    2. Marrama L
    3. Polson HE
    4. Corre S
    5. Diatta AM
    6. Diouf B
    7. Trape JF
    8. Tall A
    9. Longacre S
    10. Perraut R

    (2010) Clinical protection from falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies

    PLoS One 5:e9871.

    https://doi.org/10.1371/journal.pone.0009871

    • PubMed
    • Google Scholar
35. 1. Kellar KL
    2. Kalwar RR
    3. Dubois KA
    4. Crouse D
    5. Chafin WD
    6. Kane BE

    (2001) Multiplexed fluorescent bead-based immunoassays for quantitation of human cytokines in serum and culture supernatants

    Cytometry 45:27–36.

    https://doi.org/10.1002/1097-0320(20010901)45:1<27::AID-CYTO1141>3.0.CO;2-I

    • PubMed
    • Google Scholar
36. 1. King CL
    2. Michon P
    3. Shakri AR
    4. Marcotty A
    5. Stanisic D
    6. Zimmerman PA
    7. Cole-Tobian JL
    8. Mueller I
    9. Chitnis CE

    (2008) Naturally acquired Duffy-binding protein-specific binding inhibitory antibodies confer protection from blood-stage Plasmodium vivax infection

    PNAS 105:8363–8368.

    https://doi.org/10.1073/pnas.0800371105

    • PubMed
    • Google Scholar
37. 1. Kirkpatrick S
    2. Gelatt CD
    3. Vecchi MP

    (1983) Optimization by simulated annealing

    Science 220:671–680.

    https://doi.org/10.1126/science.220.4598.671

    • PubMed
    • Google Scholar
38. 1. Koepfli C
    2. Colborn KL
    3. Kiniboro B
    4. Lin E
    5. Speed TP
    6. Siba PM
    7. Felger I
    8. Mueller I

    (2013) A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children

    PLoS Neglected Tropical Diseases 7:e2403.

    https://doi.org/10.1371/journal.pntd.0002403

    • PubMed
    • Google Scholar
39. 1. Lin E
    2. Kiniboro B
    3. Gray L
    4. Dobbie S
    5. Robinson L
    6. Laumaea A
    7. Schöpflin S
    8. Stanisic D
    9. Betuela I
    10. Blood-Zikursh M
    11. Siba P
    12. Felger I
    13. Schofield L
    14. Zimmerman P
    15. Mueller I

    (2010) Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children

    PLoS One 5:e9047.

    https://doi.org/10.1371/journal.pone.0009047

    • PubMed
    • Google Scholar
40. 1. Longley RJ
    2. Reyes-Sandoval A
    3. Montoya-Díaz E
    4. Dunachie S
    5. Kumpitak C
    6. Nguitragool W
    7. Mueller I
    8. Sattabongkot J

    (2015) Acquisition and longevity of antibodies to Plasmodium vivax preerythrocytic antigens in Western Thailand

    Clinical and Vaccine Immunology 23:117–124.

    https://doi.org/10.1128/CVI.00501-15

    • PubMed
    • Google Scholar
41. 1. Longley RJ
    2. Sattabongkot J
    3. Mueller I

    (2016) Insights into the naturally acquired immune response to Plasmodium vivax malaria

    Parasitology 143:154–170.

    https://doi.org/10.1017/S0031182015000670

    • PubMed
    • Google Scholar
42. 1. Lu F
    2. Li J
    3. Wang B
    4. Cheng Y
    5. Kong DH
    6. Cui L
    7. Ha KS
    8. Sattabongkot J
    9. Tsuboi T
    10. Han ET

    (2014) Profiling the humoral immune responses to Plasmodium vivax infection and identification of candidate immunogenic rhoptry-associated membrane antigen (RAMA)

    Journal of Proteomics 102:66–82.

    https://doi.org/10.1016/j.jprot.2014.02.029

    • PubMed
    • Google Scholar
43. 1. Maestre A
    2. Muskus C
    3. Duque V
    4. Agudelo O
    5. Liu P
    6. Takagi A
    7. Ntumngia FB
    8. Adams JH
    9. Sim KL
    10. Hoffman SL
    11. Corradin G
    12. Velez ID
    13. Wang R

    (2010) Acquired antibody responses against Plasmodium vivax infection vary with host genotype for duffy antigen receptor for chemokines (DARC)

    PLoS One 5:e11437.

    https://doi.org/10.1371/journal.pone.0011437

    • PubMed
    • Google Scholar
44. 1. malERA Consultative Group on Vaccines

    (2011) A research agenda for malaria eradication: vaccines

    PLoS Medicine 8:e1000398.

    https://doi.org/10.1371/journal.pmed.1000398

    • PubMed
    • Google Scholar
45. 1. Mueller I
    2. Galinski MR
    3. Baird JK
    4. Carlton JM
    5. Kochar DK
    6. Alonso PL
    7. del Portillo HA

    (2009) Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite

    The Lancet Infectious Diseases 9:555–566.

    https://doi.org/10.1016/S1473-3099(09)70177-X

    • PubMed
    • Google Scholar
46. 1. Mueller I
    2. Schoepflin S
    3. Smith TA
    4. Benton KL
    5. Bretscher MT
    6. Lin E
    7. Kiniboro B
    8. Zimmerman PA
    9. Speed TP
    10. Siba P
    11. Felger I

    (2012) Force of infection is key to understanding the epidemiology of Plasmodium falciparum malaria in Papua New Guinean children

    PNAS 109:10030–10035.

    https://doi.org/10.1073/pnas.1200841109

    • PubMed
    • Google Scholar
47. 1. Mueller I
    2. Shakri AR
    3. Chitnis CE

    (2015) Development of vaccines for Plasmodium vivax malaria

    Vaccine 33:7489–7495.

    https://doi.org/10.1016/j.vaccine.2015.09.060

    • PubMed
    • Google Scholar
48. 1. Murungi LM
    2. Sondén K
    3. Llewellyn D
    4. Rono J
    5. Guleid F
    6. Williams AR
    7. Ogada E
    8. Thairu A
    9. Färnert A
    10. Marsh K
    11. Draper SJ
    12. Osier FH

    (2016) Targets and mechanisms associated with protection from severe Plasmodium falciparum malaria in kenyan children

    Infection and Immunity 84:950–963.

    https://doi.org/10.1128/IAI.01120-15

    • PubMed
    • Google Scholar
49. 1. Noland GS
    2. Jansen P
    3. Vulule JM
    4. Park GS
    5. Ondigo BN
    6. Kazura JW
    7. Moormann AM
    8. John CC

    (2015) Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood-stage antigens

    Acta Tropica 142:47–56.

    https://doi.org/10.1016/j.actatropica.2014.10.011

    • PubMed
    • Google Scholar
50. 1. Osier FH
    2. Feng G
    3. Boyle MJ
    4. Langer C
    5. Zhou J
    6. Richards JS
    7. McCallum FJ
    8. Reiling L
    9. Jaworowski A
    10. Anders RF
    11. Marsh K
    12. Beeson JG

    (2014b) Opsonic phagocytosis of Plasmodium falciparum merozoites: mechanism in human immunity and a correlate of protection against malaria

    BMC Medicine 12:108.

    https://doi.org/10.1186/1741-7015-12-108

    • PubMed
    • Google Scholar
51. 1. Osier FH
    2. Mackinnon MJ
    3. Crosnier C
    4. Fegan G
    5. Kamuyu G
    6. Wanaguru M
    7. Ogada E
    8. McDade B
    9. Rayner JC
    10. Wright GJ
    11. Marsh K

    (2014a) New antigens for a multicomponent blood-stage malaria vaccine

    Science Translational Medicine 6:247ra102.

    https://doi.org/10.1126/scitranslmed.3008705

    • PubMed
    • Google Scholar
52. 1. Phimpraphi W
    2. Paul RE
    3. Yimsamran S
    4. Puangsa-art S
    5. Thanyavanich N
    6. Maneeboonyang W
    7. Prommongkol S
    8. Sornklom S
    9. Chaimungkun W
    10. Chavez IF
    11. Blanc H
    12. Looareesuwan S
    13. Sakuntabhai A
    14. Singhasivanon P

    (2008) Longitudinal study of Plasmodium falciparum and Plasmodium vivax in a Karen population in Thailand

    Malaria Journal 7:99.

    https://doi.org/10.1186/1475-2875-7-99

    • PubMed
    • Google Scholar
53. 1. Rayner JC
    2. Corredor V
    3. Feldman D
    4. Ingravallo P
    5. Iderabdullah F
    6. Galinski MR
    7. Barnwell JW

    (2002) Extensive polymorphism in the plasmodium vivax merozoite surface coat protein MSP-3alpha is limited to specific domains

    Parasitology 125:393–405.

    https://doi.org/10.1017/S0031182002002317

    • PubMed
    • Google Scholar
54. 1. Reddy KS
    2. Amlabu E
    3. Pandey AK
    4. Mitra P
    5. Chauhan VS
    6. Gaur D

    (2015) Multiprotein complex between the GPI-anchored CyRPA with PfRH5 and PfRipr is crucial for Plasmodium falciparum erythrocyte invasion

    PNAS 112:1179–1184.

    https://doi.org/10.1073/pnas.1415466112

    • PubMed
    • Google Scholar
55. 1. Reiling L
    2. Richards JS
    3. Fowkes FJ
    4. Barry AE
    5. Triglia T
    6. Chokejindachai W
    7. Michon P
    8. Tavul L
    9. Siba PM
    10. Cowman AF
    11. Mueller I
    12. Beeson JG

    (2010) Evidence that the erythrocyte invasion ligand PfRh2 is a target of protective immunity against Plasmodium falciparum malaria

    The Journal of Immunology 185:6157–6167.

    https://doi.org/10.4049/jimmunol.1001555

    • PubMed
    • Google Scholar
56. 1. Richards JS
    2. Arumugam TU
    3. Reiling L
    4. Healer J
    5. Hodder AN
    6. Fowkes FJ
    7. Cross N
    8. Langer C
    9. Takeo S
    10. Uboldi AD
    11. Thompson JK
    12. Gilson PR
    13. Coppel RL
    14. Siba PM
    15. King CL
    16. Torii M
    17. Chitnis CE
    18. Narum DL
    19. Mueller I
    20. Crabb BS
    21. Cowman AF
    22. Tsuboi T
    23. Beeson JG

    (2013) Identification and prioritization of merozoite antigens as targets of protective human immunity to Plasmodium falciparum malaria for vaccine and biomarker development

    The Journal of Immunology 191:795–809.

    https://doi.org/10.4049/jimmunol.1300778

    • PubMed
    • Google Scholar
57. 1. Richards JS
    2. Stanisic DI
    3. Fowkes FJ
    4. Tavul L
    5. Dabod E
    6. Thompson JK
    7. Kumar S
    8. Chitnis CE
    9. Narum DL
    10. Michon P
    11. Siba PM
    12. Cowman AF
    13. Mueller I
    14. Beeson JG

    (2010) Association between naturally acquired antibodies to erythrocyte-binding antigens of Plasmodium falciparum and protection from malaria and high-density parasitemia

    Clinical Infectious Diseases 51:e50–e60.

    https://doi.org/10.1086/656413

    • PubMed
    • Google Scholar
58. 1. Robinson LJ
    2. Wampfler R
    3. Betuela I
    4. Karl S
    5. White MT
    6. Li Wai Suen CS
    7. Hofmann NE
    8. Kinboro B
    9. Waltmann A
    10. Brewster J
    11. Lorry L
    12. Tarongka N
    13. Samol L
    14. Silkey M
    15. Bassat Q
    16. Siba PM
    17. Schofield L
    18. Felger I
    19. Mueller I

    (2015) Strategies for understanding and reducing the Plasmodium vivax and Plasmodium ovale hypnozoite reservoir in Papua New Guinean children: a randomised placebo-controlled trial and mathematical model

    PLOS Medicine 12:e1001891.

    https://doi.org/10.1371/journal.pmed.1001891

    • PubMed
    • Google Scholar
59. 1. RTS,S Clinical Trials Partnership

    (2014) Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites

    PLoS Medicine 11:e1001685.

    https://doi.org/10.1371/journal.pmed.1001685

    • PubMed
    • Google Scholar
60. 1. Salman AM
    2. Montoya-Díaz E
    3. West H
    4. Lall A
    5. Atcheson E
    6. Lopez-Camacho C
    7. Ramesar J
    8. Bauza K
    9. Collins KA
    10. Brod F
    11. Reis F
    12. Pappas L
    13. González-Cerón L
    14. Janse CJ
    15. Hill AVS
    16. Khan SM
    17. Reyes-Sandoval A

    (2017) Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

    Scientific Reports 7:46482.

    https://doi.org/10.1038/srep46482

    • PubMed
    • Google Scholar
61. 1. Stanisic DI
    2. Fowkes FJ
    3. Koinari M
    4. Javati S
    5. Lin E
    6. Kiniboro B
    7. Richards JS
    8. Robinson LJ
    9. Schofield L
    10. Kazura JW
    11. King CL
    12. Zimmerman P
    13. Felger I
    14. Siba PM
    15. Mueller I
    16. Beeson JG

    (2015) Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response

    Infection and Immunity 83:646–660.

    https://doi.org/10.1128/IAI.02398-14

    • PubMed
    • Google Scholar
62. 1. Stanisic DI
    2. Javati S
    3. Kiniboro B
    4. Lin E
    5. Jiang J
    6. Singh B
    7. Meyer EV
    8. Siba P
    9. Koepfli C
    10. Felger I
    11. Galinski MR
    12. Mueller I

    (2013) Naturally acquired immune responses to P. vivax merozoite surface protein 3α and merozoite surface protein 9 are associated with reduced risk of P. vivax malaria in young Papua New Guinean children

    PLoS Neglected Tropical Diseases 7:e2498.

    https://doi.org/10.1371/journal.pntd.0002498

    • PubMed
    • Google Scholar
63. 1. Tanner M
    2. Greenwood B
    3. Whitty CJ
    4. Ansah EK
    5. Price RN
    6. Dondorp AM
    7. von Seidlein L
    8. Baird JK
    9. Beeson JG
    10. Fowkes FJ
    11. Hemingway J
    12. Marsh K
    13. Osier F

    (2015) Malaria eradication and elimination: views on how to translate a vision into reality

    BMC Medicine 13:167.

    https://doi.org/10.1186/s12916-015-0384-6

    • PubMed
    • Google Scholar
64. 1. Teo A
    2. Feng G
    3. Brown GV
    4. Beeson JG
    5. Rogerson SJ

    (2016) Functional Antibodies and Protection against Blood-stage Malaria

    Trends in Parasitology 32:887–898.

    https://doi.org/10.1016/j.pt.2016.07.003

    • PubMed
    • Google Scholar
65. 1. Tongren JE
    2. Drakeley CJ
    3. McDonald SL
    4. Reyburn HG
    5. Manjurano A
    6. Nkya WM
    7. Lemnge MM
    8. Gowda CD
    9. Todd JE
    10. Corran PH
    11. Riley EM

    (2006) Target antigen, age, and duration of antigen exposure independently regulate immunoglobulin G subclass switching in malaria

    Infection and Immunity 74:257–264.

    https://doi.org/10.1128/IAI.74.1.257-264.2006

    • PubMed
    • Google Scholar
66. 1. Tonkin ML
    2. Arredondo SA
    3. Loveless BC
    4. Serpa JJ
    5. Makepeace KA
    6. Sundar N
    7. Petrotchenko EV
    8. Miller LH
    9. Grigg ME
    10. Boulanger MJ

    (2013) Structural and biochemical characterization of Plasmodium falciparum 12 (Pf12) reveals a unique interdomain organization and the potential for an antiparallel arrangement with Pf41

    Journal of Biological Chemistry 288:12805–12817.

    https://doi.org/10.1074/jbc.M113.455667

    • PubMed
    • Google Scholar
67. 1. Tran TM
    2. Oliveira-Ferreira J
    3. Moreno A
    4. Santos F
    5. Yazdani SS
    6. Chitnis CE
    7. Altman JD
    8. Meyer EV
    9. Barnwell JW
    10. Galinski MR

    (2005) Comparison of IgG reactivities to Plasmodium vivax merozoite invasion antigens in a Brazilian Amazon population

    The American Journal of Tropical Medicine and Hygiene 73:244–255.

    https://doi.org/10.4269/ajtmh.2005.73.244

    • PubMed
    • Google Scholar
68. 1. Tsuboi T
    2. Takeo S
    3. Arumugam TU
    4. Otsuki H
    5. Torii M

    (2010) The wheat germ cell-free protein synthesis system: a key tool for novel malaria vaccine candidate discovery

    Acta Tropica 114:171–176.

    https://doi.org/10.1016/j.actatropica.2009.10.024

    • PubMed
    • Google Scholar
69. 1. van Ooij C
    2. Withers-Martinez C
    3. Ringel A
    4. Cockcroft S
    5. Haldar K
    6. Blackman MJ

    (2013) Identification of a Plasmodium falciparum phospholipid transfer protein

    Journal of Biological Chemistry 288:31971–31983.

    https://doi.org/10.1074/jbc.M113.474189

    • PubMed
    • Google Scholar
70. 1. White MT
    2. Griffin JT
    3. Riley EM
    4. Drakeley CJ
    5. Moorman AM
    6. Sumba PO
    7. Kazura JW
    8. Ghani AC
    9. John CC

    (2011) Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

    Proceedings. Biological sciences 278:1298–1305.

    https://doi.org/10.1098/rspb.2010.1697

    • PubMed
    • Google Scholar
71. Report

    1. WHO

    (2014)

    World Malaria Report 2014

    Geneva, Switzerland: World Health Organization.

    • Google Scholar
72. 1. Wipasa J
    2. Suphavilai C
    3. Okell LC
    4. Cook J
    5. Corran PH
    6. Thaikla K
    7. Liewsaree W
    8. Riley EM
    9. Hafalla JC

    (2010) Long-lived antibody and B Cell memory responses to the human malaria parasites, Plasmodium falciparum and Plasmodium vivax

    PLoS Pathogens 6:e1000770.

    https://doi.org/10.1371/journal.ppat.1000770

    • PubMed
    • Google Scholar
73. 1. Wongkidakarn S
    2. McHenry AM
    3. Sattabongkot J
    4. Adams JH
    5. Chootong P

    (2016) Strain-Transcending Inhibitory Antibodies against Homologous and Heterologous Strains of Duffy Binding Protein region II

    PLoS One 11:e0154577.

    https://doi.org/10.1371/journal.pone.0154577

    • PubMed
    • Google Scholar
74. 1. Yadava A
    2. Sattabongkot J
    3. Washington MA
    4. Ware LA
    5. Majam V
    6. Zheng H
    7. Kumar S
    8. Ockenhouse CF

    (2007) A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites

    Infection and Immunity 75:1177–1185.

    https://doi.org/10.1128/IAI.01667-06

    • PubMed
    • Google Scholar
75. 1. Yildiz Zeyrek F
    2. Palacpac N
    3. Yuksel F
    4. Yagi M
    5. Honjo K
    6. Fujita Y
    7. Arisue N
    8. Takeo S
    9. Tanabe K
    10. Horii T
    11. Tsuboi T
    12. Ishii KJ
    13. Coban C

    (2011) Serologic markers in relation to parasite exposure history help to estimate transmission dynamics of Plasmodium vivax

    PLoS One 6:e28126.

    https://doi.org/10.1371/journal.pone.0028126

    • PubMed
    • Google Scholar
76. 1. Zeyrek FY
    2. Babaoglu A
    3. Demirel S
    4. Erdogan DD
    5. Ak M
    6. Korkmaz M
    7. Coban C

    (2008)

    Analysis of naturally acquired antibody responses to the 19-kd C-terminal region of merozoite surface protein-1 of Plasmodium vivax from individuals in Sanliurfa, Turkey

    The American journal of tropical medicine and hygiene 78:729–732.

    • PubMed
    • Google Scholar

Author details

1. Camila Tenorio França

   1. Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
   2. Department of Medical Biology, University of Melbourne, Parkville, Australia

   Contribution

   Formal analysis, Validation, Investigation, Visualization, Methodology, Writing—original draft

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-5885-4410

2. Michael T White

   1. Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
   2. MRC Center for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom

   Contribution

   Formal analysis, Visualization, Methodology, Writing—original draft

   Competing interests

   No competing interests declared

3. Wen-Qiang He

   1. Department of Medical Biology, University of Melbourne, Parkville, Australia
   2. Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

   Contribution

   Investigation, Writing—review and editing

   Competing interests

   No competing interests declared

4. Jessica B Hostetler

   1. Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
   2. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States

   Contribution

   Resources, Writing—review and editing

   Competing interests

   No competing interests declared

5. Jessica Brewster

   Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

   Contribution

   Validation, Investigation

   Competing interests

   No competing interests declared

6. Gabriel Frato

   Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States

   Contribution

   Resources, Methodology

   Competing interests

   No competing interests declared

7. Indu Malhotra

   Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States

   Contribution

   Resources, Methodology

   Competing interests

   No competing interests declared

8. Jakub Gruszczyk

   Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

   Contribution

   Resources, Writing—review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-4536-2964

9. Christele Huon

   Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Paris, France

   Contribution

   Resources, Methodology

   Competing interests

   No competing interests declared

10. Enmoore Lin

    Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea

    Contribution

    Resources, Methodology

    Competing interests

    No competing interests declared

11. Benson Kiniboro

    Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea

    Contribution

    Resources, Methodology

    Competing interests

    No competing interests declared

12. Anjali Yadava

    Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, United States

    Contribution

    Resources, Writing—review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0002-6751-954X

13. Peter Siba

    Malaria Immuno-Epidemiology Unit, PNG Institute of Medical Research, Yagaum, Papua New Guinea

    Contribution

    Conceptualization, Resources, Funding acquisition

    Competing interests

    No competing interests declared

14. Mary R Galinski

    1. International Center for Malaria Research, Education, and Development, Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, United States
    2. Infectious Diseases Division, Department of Medicine, Emory University, Atlanta, United States

    Contribution

    Resources, Writing—review and editing

    Competing interests

    No competing interests declared

15. Julie Healer

    1. Department of Medical Biology, University of Melbourne, Parkville, Australia
    2. Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

    Contribution

    Resources, Writing—review and editing

    Competing interests

    No competing interests declared

16. Chetan Chitnis

    1. Malaria Parasite Biology and Vaccines Unit, Institut Pasteur, Paris, France
    2. International Centre for Genetic Engineering and Biotechnology, New Delhi, India

    Contribution

    Resources, Writing—review and editing

    Competing interests

    No competing interests declared

17. Alan F Cowman

    1. Department of Medical Biology, University of Melbourne, Parkville, Australia
    2. Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

    Contribution

    Resources, Funding acquisition, Writing—review and editing

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-5145-9004

18. Eizo Takashima

    Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, United States

    Contribution

    Resources, Writing—review and editing

    Competing interests

    No competing interests declared

19. Takafumi Tsuboi

    Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan

    Contribution

    Resources, Funding acquisition, Writing—review and editing

    Competing interests

    No competing interests declared

20. Wai-Hong Tham

    1. Department of Medical Biology, University of Melbourne, Parkville, Australia
    2. Division of Infection and Immunity, Walter and Eliza Hall Institute, Parkville, Australia

    Contribution

    Resources, Funding acquisition, Writing—review and editing

    Competing interests

    No competing interests declared

21. Rick M Fairhurst

    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, United States

    Contribution

    Resources, Funding acquisition, Writing—review and editing

    Competing interests

    No competing interests declared

22. Julian C Rayner

    Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, United Kingdom

    Contribution

    Resources, Funding acquisition, Writing—review and editing

    Competing interests

    No competing interests declared

23. Christopher L King

    Center for Global Health and Diseases, Case Western Reserve University, Cleveland, United States

    Contribution

    Conceptualization, Resources, Funding acquisition, Methodology, Writing—review and editing

    Competing interests

    No competing interests declared

24. Ivo Mueller

    1. Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia
    2. Department of Medical Biology, University of Melbourne, Parkville, Australia
    3. Malaria Parasites and Hosts Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France
    4. Barcelona Institute of Global Health, Barcelona, Spain

    Contribution

    Conceptualization, Resources, Data curation, Formal analysis, Supervision, Funding acquisition, Methodology, Project administration, Writing—review and editing

    For correspondence

    mueller@wehi.edu.au

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0001-6554-6889

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