P10. A Longitudinal Study on the Dynamics of Plasma Neutralising Antibodies and Determinants in HIV-2 Infection

Hans Norrgren1, Gülşen Özkaya Şahin2, Sara Karlson3, Antonio Biague4, Fredrik Månsson5, Marianne Jansson3, and Sweden-Guinea-Bissau Cohort Research Group
Affiliates: 1Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund. 2Clinical Microbiology, Laboratory Medicine Skåne, Lund. 3Department of Laboratory Medicine, Lund University, Lund. 4National Public Health Laboratory, Bissau, Guinea-Bissau. 5Department of Clinical Sciences, Lund University, Malmö, Sweden

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Background
The majority of HIV-2-infected individuals seems to survive as elite controllers. Therefore, HIV-2 infection represents a model for the studies of immune responses that may control an HIV infection, and possibly give leads towards a functional cure. Plasma neutralising antibodies (NAb) are thought to play a central role in HIV-2 evolution and pathogenesis. In 1990 we started an open cohort of Police officers in Guinea-Bissau, and in this study we wanted to investigate the dynamics of the NAb response during natural course of HIV-2 infection and what are the modulators of broad and potent NAb response?

Materials and methods
Fourty-six plasma from 15 HIV-2 seroincident individuals living in Guinea-Bissau were obtained between 1992-2010. For the neutralization assay, GHOST(3)-CCR5 cell line and five HIV-2 isolates derived from West Africa were used. For analysis of breadth and potency of NAb, plasma was titrated starting at 1:20 dilution. The cut-off for neutralization was 30%.

Results
Based on mean CD4+ T cell count per individual the participants were subgrouped as immunocompetent (mean ≥500/μl) or immunodeficient (mean <500/μl). Median seroconversion age was found to be lower in the immunocompetent group compared to the immunodeficient group (28 vs 38 years, respectively, p=0.014). Broad and potent NAb response arose in all HIV-2 infected participants against 5 HIV-2 isolates during the first year of infection. Furthermore, the NAb titers tended to increase 10-100 times during the follow-up period. NAb response at the end of the follow-up period was significantly broader and more potent in the immunocompetent group (breadth 4.3 vs 2.9, p=0.01 and potency 200000 vs 30000, p=0.04, respectively). Univariate correlation analyses revealed that age at seroconversion, duration of infection and CD4+ T cell count modulate breadth and potency of NAb response.

Discussion
Broadly NAb response in HIV-1 infection arises only in around 15% of patients after 2-4 years of infection. In addition, NAb response tends to fluctuate with low potency. Contrarily, here we show that broad and potent NAb response develops in all HIV-2 infected participants during the first year of infection and tends to be persistent.

Conclusion
These results may provide insights into the role of potently persistent neutralizing humoral immune response on mild outcome of HIV-2 infection. The current study represents the most comprehensive longitudinal study of NAb response in HIV-2 infected individuals with known seroconversion time and may help us to develop an effective vaccine against HIV-1.