Impact of ethnicity and geographic location on HIV vaccine outcome?
LIN L. 1, CHACHAGE M. 2,3,4, FERTE T. 5, CASTEANO C. 6, HORVATH A. 4, HOELSCHER M. 4,7, HELD K. 4,7, LUCAS J. 1, LAUMOND G. 1, SCHMIDT S. 1, CARAPITO R. 1, CHURCHYARD G. 8,9, KEEFER M. 10, MOODIE Z. 11, VIEGAS E. 6, GELDMACHER C. 4,7, LHOMME E. 5,12, MOOG C. 1,12
1 1. UMR_S 1109 INSERM, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; 2 2. NIMR-Mbeya Medical Research Center (MMRC), Mbeya, Tanzania; 3 3. University of Dar es Salaam -Mbeya College of Health and Allied Sciences (UDSM-MCHAS), Mbeya, Tanzania; 4 4. Division of Infectious Diseases and Tropical Medicine, Medical Center of the University of Munich (LMU), Munich, Germany; 5 5. University of Bordeaux, Department of Public Health, Inserm Bordeaux Population Health Research Centre, Inria SISTM, Bordeaux, France; 6 6. Instituto Nacional de Sau´de (INS), Maputo, Mozambique; 7 7. German Center for Infection Research (DZIF), partner site Munich, Munich, Germany; 8 8. Aurum Institute for Health Research, Klerksdorp, South Africa; 9 9. Centre for AIDS Programme of Research in South Africa (CAPRISA), University of Kwa-Zulu Natal, Durban, South Africa; 10 10. Department of Medicine, University of Rochester School of Medicine & Dentistry, Rochester, New York, United States; 11 11. Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States; 12 12. Vaccine Research Institute (VRI), Créteil, France
Despite numerous preventive HIV vaccine trials performed, only the RV144 Thai trial showed a low but significantly decreased risk of infection. This protection could be associated with the induction of Fc-mediated antibody inhibitory functions. Attempts to improve this protection with a clade C-adapted version of the regimen did not succeed. As Fc-receptor polymorphisms varied according to ethnicity, this may have played a role given the different populations.
The role of ethnicity and geographic region was analyzed for the HVTN 204 vaccine trial of multivalent DNA-HIV prime immunizations followed by a rAd5-HIV boost in Blacks from South Africa (n=72), Blacks (n=12) and Whites (n=49) from USA. Total and specific antibody responses were measured at month 0 (M0) and one month after the final boost (M7). Antibody functions, neutralizing and antibody-dependent cellular cytotoxicity (ADCC), were determined by conventional TZM-bl and ADCC-LUC assay, respectively. Fc-receptor polymorphisms were genotyped by customised Taqman assays.
Compared to US Whites, Black South Africans had higher total IgG (p<0.001) and IgA (p=0.026). Black South Africans had lower HIV-specific antibodies (p<0.001), lower neutralization against tier 1 virus MW965.26 (p=0.007), and lower frequency of the AA rs10800309 FcR polymorphism (p=0.003). However, as Black South Africans displayed lower HIV-specific backgrounds (p<0.001), these differences were levelled when calculating the delta (M7-M0). Multivariate analysis showed that the delta of total IgA, IgG and HIV-specific antibodies was correlated with the FcR polymorphism independently of other parameters like sex, age, race, or geographical region. Geographical region and gender impact the delta of total IgG and IgA, respectively. As ADCC was not detected, its impact on ethnicity could not be determined.
The difference of antibody responses induced by HVTN 204 vaccine according to the genetic and geographic background support further investigation. Such results may give new insights for future “vaccine-specific design”, customized according to ethnicity/country specificities.