Systematic comparison of antigenic regions targeted by vaccine-induced IgG responses in different HIV vaccination trials.
Abteilung für Infektions- und Tropenmedizin / Center For International Health, Infection & Immunity
In the Rhesus macaque model, Env binding IgG is the best predictor of vaccine induced protection during challenge with a heterologous and highly pathogenic SIV strain (Barouch et al. 2012, Nature). During the Rv144 trial, vaccine induced IgG antibodies binding to scaffolded-V1V2 protein (Haynes et al. 2012 NEJM) or a certain linear EnvV2 peptide (Gottardo et al 2013, PLOSone; Zolla-Pazner et al. 2013; PLOSone) were the only correlate of protection from HIV acquisition, whereas Env-binding IgA correlated with increased risk of aquisition among vaccines. The potential importance of the V1V2 region-specific IgG is further supported by HIV genetic sequencing data of Rv144 break through viruses, suggesting that a moderate “sieve effect” of the vaccine antibody response might have selected for viruses with specific point mutations (33% of vaccine recipients versus 17% in Placebo recipients) in this region (Rolland et al 2012, Nature). Ideally, vaccines against variable viruses, such as HIV, should induce immune responses which target all variants of a vulnerable antigenic region, such as HIV_EnvV2, to prevent infection by any variant virus. It remains however largely unclear how best to design vaccines to specifically target the most vulnerable regions of the virus. Mapping of Envelope-specific IgG responses during different vaccine trials testing different prime/boos strategies can help to elucidate how IgG responses can be focused towards a region of specific interest.
Within the proposed project, we will thus simultaneously map HIV Envelope antigenic regions that are targeted after vaccination in different human vaccine trials using different combinations of vaccine vectors (DNA, MVA, Adenovirus 5 based vectors, recombinant Protein) The proposed study will also serve as a starting point to elucidate whether vaccine-induced antibody responses can be focused on antigenic regions of specific interest.
Clinical samples: Plasma samples from 7 HIV vaccine trials were received and are stored at the Institute.
Methodology: The HIV Envelope Peptide array is fully established in the laboratory. It tests 1050 peptides in triplicates simultaneously. The data analyses pipeline is already well established in the laboratory.
Publication of results: YES
Timelines: ca. 6-9 months full time
Geschätzte Dauer: 9 Monate