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HIV-1 Vaccine Sequences Impact V1V2 Antibody Responses: A Comparison of Two Poxvirus Prime gp120 Boost Vaccine Regimens.

Scientific reports | 2020

In the RV144 trial, vaccine-induced V1V2 IgG correlated with decreased HIV-1 risk. We investigated circulating antibody specificities in two phase 1 poxvirus prime-protein boost clinical trials conducted in South Africa: HVTN 097 (subtype B/E) and HVTN 100 (subtype C). With cross-subtype peptide microarrays and multiplex binding assays, we probed the magnitude and breadth of circulating antibody responses to linear variable loop 2 (V2) and conformational V1V2 specificities. Antibodies targeting the linear V2 epitope, a correlate of decreased HIV-1 risk in RV144, were elicited up to 100% and 61% in HVTN 097 and HVTN 100, respectively. Despite higher magnitude of envelope-specific responses in HVTN 100 compared to HVTN 097 (p'sā€‰<ā€‰0.001), the magnitude and positivity for V2 linear epitope and V1V2 proteins were significantly lower in HVTN 100 compared to HVTN 097. Meanwhile, responses to other major linear epitopes including the variable 3 (V3) and constant 5 (C5) epitopes were higher in HVTN 100 compared to HVTN 097. Our data reveal substantial differences in the circulating antibody specificities induced by vaccination in these two canarypox prime-protein boost trials. Our findings suggest that the choice of viral sequences in prime-boost vaccine regimens, and potentially adjuvants and immunogen dose, influence the elicitation of V2-specific antibodies.

Pubmed ID: 32034163 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI069519
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI069469
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI068614
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI068618
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI069453
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI068635
  • Agency: NIAID NIH HHS, United States
    Id: UM1 AI069422
  • Agency: NIAID NIH HHS, United States
    Id: P30 AI064518

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Mapix (tool)

RRID:SCR_002723

System control software used for data acquisition and analysis for microarray images.

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pepStat (tool)

RRID:SCR_006240

Software for statistical analysis of peptide microarrays. It uses an integrated analytical method for analyzing peptide microarray antibody binding data, from normalization through subject-specific positivity calls and data integration and visualization.

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BAMA (tool)

RRID:SCR_009071

Software application to select a trait-associated subset of markers among many candidates. The program is based on Bayesian modeling/estimation and it suits for both quantitative and qualitative traits. It can handle bi- and multiallelic markers as well as applied in situations where part of the marker genotypes may be missing. As an output of the program, one obtains posterior estimate of number and positions of trait-associated markers. (entry from Genetic Analysis Software)

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