Seroconversion to Pandemic (H1N1) 2009 Virus and Cross-Reactive Immunity to Other Swine Influenza Viruses

To assess herd immunity to swine influenza viruses, we determined antibodies in 28 paired serum samples from participants in a prospective serologic cohort study in Hong Kong who had seroconverted to pandemic (H1N1) 2009 virus. Results indicated that infection with pandemic (H1N1) 2009 broadens cross-reactive immunity to other recent subtype H1 swine viruses.

To assess herd immunity to swine infl uenza viruses, we determined antibodies in 28 paired serum samples from participants in a prospective serologic cohort study in Hong Kong who had seroconverted to pandemic (H1N1) 2009 virus. Results indicated that infection with pandemic (H1N1) 2009 broadens cross-reactive immunity to other recent subtype H1 swine viruses. P andemic (H1N1) 2009 was able to spread globally because it was antigenically divergent from contemporary human seasonal subtype H1N1 infl uenza viruses (1). Because we now recognize that pandemics can arise from infl uenza subtypes endemic in humans, it is essential that subtypes, H1 and H3 swine viruses be considered potential future pandemic candidates, together with other avian virus subtypes such as H2, H5, or H9. Thus, it becomes imperative to investigate herd immunity in humans to swine and avian infl uenza viruses of subtypes H1 and H3.
Infl uenza virus subtypes H1 and H3 of diverse lineages are endemic in swine and are globally widespread. Eurasian avian-like swine H1 viruses are found in Europe; triple reassortant swine subtypes H1 and H3 viruses remain entrenched in North America (2). In China, we have demonstrated the co-circulation of these lineages together with classical swine (CS) subtype H1 viruses and also documented the emergence of antigenically variant reassortant viruses with gene segments of >2 of these lineages. We previously showed a lack of herd immunity in humans to some of these swine virus lineages in serum samples collected before the 2009 pandemic (3). However, the spread of pandemic (H1N1) 2009 worldwide may generate cross-reactive herd immunity to some of these swine virus lineages, making them less likely candidates for future pandemics. In this study, we assessed the relationship between seroconversion to pandemic (H1N1) 2009 and cross-reactive antibody responses to other major subtype H1 swine viruses in humans.

The Study
Twenty-eight paired serum samples from a prospective serologic cohort study in Hong Kong, in which participants seroconverted to the pandemic (H1N1) 2009 virus, were selected to represent persons of diverse ages (median 39.5 years, range 8-74 years). Details of the serologic cohort have been reported elsewhere (4). The fi rst (prepandemic or baseline) serum sample from each person was collected during July-August 2009, and the second (postpandemic or convalescent-phase) serum sample was collected during November 2009-February 2010. The peak of the fi rst pandemic wave in Hong Kong occurred in September 2009. Subtype H1 swine infl uenza viruses, representative of CS, Eurasian avian-like swine (EA), triple reassortant swine (TRIG), pandemic (H1N1) 2009 viruses, and selected reassortants between these lineages with diverse antigenic profi les, were selected from our surveillance of swine infl uenza viruses in China (3). Relevant viruses from other geographic regions were also included. Each pair of baseline and convalescent-phase serum samples was tested for antibodies by microneutralization tests using each swine infl uenza virus. The profi le of serologic responses to these swine viruses is shown in the Figure. In accordance with our selection criteria, all 28 persons seroconverted (rise in antibody titer from <20 to >40) to the pandemic (H1N1) 2009 virus; follow-up antibody titers ranged from 40 to 320 ( Figure). As expected, no serologic response occurred to seasonal infl uenza (H1N1) virus A/HK/400599/2008. Because the postpandemic serum samples were collected 2-5 months after the peak of the pandemic, waning of antibody titers over a few months is expected to be relatively modest (5). Notably, although few of the prepandemic serum samples tested had evidence of antibody titers >40 to any of the swine H1 viruses, the convalescent-phase serum sample of most persons had detectable antibody titers to other infl uenza viruses: CS (H1N1) Sw4167 (93% seropositive at a titer of >40; geometric mean titer [GMT] 121.9) and Sw1304 (86%; GMT 107.7); TRIG Sw1110 (75%; GMT 50); EA SwNS29 (46%; GMT 40), and an antigenically variant EA virus from Hong Kong that had acquired a nonstructural gene segment from TRIG virus by reassortment (57%; GMT 53) (Table).
Because Hong Kong is a heavily urbanized environment, exposure of the study volunteers to live

Conclusions
In this study, we focused on defi ning the effects of seroconversion to pandemic (H1N1) 2009 on serologic cross-reactivity to other swine subtype H1 viruses. The next step should be to ascertain herd immunity to these swine infl uenza viruses in different population groups. We chose not to do this at this stage because the pandemic virus is still circulating among human populations, and seroprevalence is likely to continue to increase in different age groups over the next few years. Therefore, studying the effect of seroconversion to pandemic (H1N1) 2009 on cross-reaction to other swine infl uenza viruses would provide more meaningful information at this stage.
The results of our study suggest that the spread of pandemic (H1N1) 2009 in the population is broadening the serologic cross-reactivity and immunity in humans to other swine infl uenza viruses. However, gaps in immunity to selected swine infl uenza subtype H1 viruses remain (e.g., Sw112), at least as ascertained by neutralization antibody titers. We recognize, however, that neutralization tests do not capture all aspects of herd immunity in a population. Thus, our fi ndings only serve to focus attention on the need for further study of population immunity to viruses such as Sw112. In general, these fi ndings highlight the need for enhanced global surveillance of swine infl uenza viruses for the systematic assessment of human herd immunity to novel swine strains and to facilitate the development of routine (evidence-based) procedures for the ranking of known strains in terms of their pandemic risk.