Zusammenfassung
In klinischen Studien zur Untersuchung neuer Impfstoffkandidaten wird zunächst Sicherheit, Verträglichkeit und teilweise auch Immunogenität des zukünftigen Impfstoffes erforscht. Immunologische Versuchsanordnungen müssen je nach Impfstoff etabliert und validiert werden und gegebenenfalls für die Durchführung in multizentrischen Studien weiterentwickelt werden. Die Etablierung von verschiedenen Versuchsanordnungen und die Anpassung an weltweit unterschiedliche Arbeitsbedingungen stellen Herausforderungen an die beteiligten Wissenschaftler. Im vorliegenden Artikel wird dieser Prozess am Beispiel einer kürzlich im Institut für Tropenmedizin in Tübingen, Deutschland durchgeführten Impfstudie zur Erprobung eines neuen Malaria Impfstoffkandidaten erläutert. Die Arbeitsgruppe für klinische Forschung und Immunologie ist hier die Schnittstelle für die Etablierung von immunologischen Untersuchungsmethoden und die Anwendung in klinischen Studien.
Summary
Clinical trials for new vaccine candidates evaluate safety and tolerability of future vaccines. In some studies immunogenicity is an additional exploratory aim. For this purpose immunological assays have to be established and further developed for future multicentre studies. The implementation of immunological assays and the different logistic conditions worldwide display new challenges for scientists working in this field. This article shows this process on a recently conducted phase Ia clinical trial at the Institute of Tropical Medicine in Tübingen, Germany, to evaluate the safety and immunogenicity of a new malaria vaccine candidate. The group for clinical trials and immunology is the interphase for the establishment of immunological assays and their implementation in clinical trials.
Article PDF
References
Nagill R, Mahajan R, Sharma M, Kaur S (2009) Induction of cellular and humoral responses by autoclaved and heat-killed antigen of Leishmania donovani in experimental visceral leishmaniasis. Parasitol Int 58: 359–66
Bhaumik SK, Naskar K, De T (2009) Complete protection against experimental visceral leishmaniasis with complete soluble antigen from attenuated Leishmania donovani promastigotes involves Th1-immunity and down-regulation of IL-10. Eur J Immunol 39: 2146–60
Kur J, Holec-Gasior L, Hiszczyńska-Sawicka E (2009) Current status of toxoplasmosis vaccine development. Expert Rev Vaccines 8: 791–808
Haolla FA, Claser C, de Alencar BC, Tzelepis F, de Vasconcelos JR, de Oliveira G, et al (2009) Vaccine 27: 5644–53
Diemert DJ, Bethony JM, Hotez PJ (2008) Hookworm vaccines. Clin Infect Dis 46: 282–8
Richards JS, Beeson JG (2009) The future for blood-stage vaccines against malaria. Immunol Cell Biol 87: 377–90
Todryk SM, Hill AV (2007) Malaria vaccines: the stage we are at. Nat Rev Microbiol 5: 487–90
Lell B, Agnandji S, von Glasenapp I, Haertle S, Oyakhiromen S, Issifou S, et al (2009) A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon. PLoS One 4: e7611
Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, et al (2008) Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med 359: 2521–32
Abdulla S, Oberholzer R, Juma O, Kubhoja S, Machera F, Membi C, et al (2008) Safety and immunogenicity of RTS,S/AS02D malaria vaccine in infants. N Engl J Med 359: 2533–44
Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J, et al (2004) Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial. Lancet 364: 1411–20
Esen M, Kremsner PG, Schleucher R, Gässler M, Imoukhuede EB, Imbault N, et al (2009) Safety and immunogenicity of GMZ2 – a MSP3-GLURP fusion protein malaria vaccine candidate. Vaccine 27: 6862–8
Metzger WG, Vivas-Martínez S, Rodriguez I, Gonçalves J, Bongard E, Fanello CL, et al (2008) Malaria diagnosis under field conditions in the Venezuelan Amazon. Trans R Soc Trop Med Hyg 102: 20–4
Corran PH, Cook J, Lynch C, Leendertse H, Manjurano A, Griffin J, et al (2008) Dried blood spots as a source of anti-malarial antibodies for epidemiological studies. Malar J 7: 195
Hermsen CC, Verhage DF, Telgt DS, Teelen K, Bousema JT, Roestenberg M, et al (2007) Glutamate-rich protein (GLURP) induces antibodies that inhibit in vitro growth of Plasmodium falciparum in a phase 1 malaria vaccine trial. Vaccine 25: 2930–40
Bernasconi NL, Traggiai E, Lanzavecchia A (2002) Maintenance of serological memory by polyclonal activation of human memory B-cells. Science 298: 2199–202
Harris JB, Podolsky MJ, Bhuiyan TR, Chowdhury F, Khan AI, Larocque RC, et al (2009) Immunologic responses to Vibrio cholerae in patients co-infected with intestinal parasites in Bangladesh. PLoS Negl Trop Dis 3: e403
Cooper PJ, Chico ME, Losonsky G, Sandoval C, Espinel I, Sridhara R, et al (2000) Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR. J Infect Dis 182: 1199–206
van Riet E, Adegnika AA, Retra K, Vieira R, Tielens AG, Lell B, et al (2007) Cellular and humoral responses to influenza in Gabonese children living in rural and semi-urban areas. J Infect Dis 196: 1671–8
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Esen, M. Assessment of humoral immune responses in malaria vaccine trials. Wien Klin Wochenschr 122 (Suppl 1), 4–6 (2010). https://doi.org/10.1007/s00508-010-1325-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00508-010-1325-1