Journal
VACCINES
Volume 8, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/vaccines8020171
Keywords
HIV-1 vaccine; Recombinant Vaccinia virus; envelope glycoproteins; non-B-non-C clades; BALB/c mice; New Zealand White rabbits; broadly neutralizing antibodies
Categories
Funding
- Genese Program, Gilead Sciences, Portugal [PGG/015/2016, PGG/02/2015]
- Fundacao para a Ciencia e Tecnologia (FCT), Portugal [SFRH/BD/87488/2012, SFRH/BD/70715/2010, SFRH/BPD/76225/2011]
- FCT
- Aga Khan Development Network (AKDN)-Portugal Collaborative Research Network in Portuguese speaking countries in Africa [332821690]
- European & Developing Countries Clinical Trials Partnership (EDCTP), UE (LIFE project) [RIA2016MC-1615]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/70715/2010, SFRH/BD/87488/2012] Funding Source: FCT
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Development of new immunogens eliciting broadly neutralizing antibodies (bNAbs) is a main priority for the HIV-1 vaccine field. Envelope glycoproteins from non-B-non-C HIV-1clades have not been fully explored as components of a vaccine. We produced Vaccinia viruses expressing a truncated version of gp120 (gp120t) from HIV-1 clades CRF02_AG, H, J, B, and C and examined their immunogenicity in mice and rabbits. Mice primed with the recombinant Vaccinia viruses and boosted with the homologous gp120t or C2V3C3 polypeptides developed antibodies that bind potently to homologous and heterologous envelope glycoproteins. Notably, a subset of mice immunized with the CRF02_AG-based envelope immunogens developed a cross-reactive neutralizing response against tier 2 HIV-1 Env-pseudoviruses and primary isolates. Rabbits vaccinated with the CRF02_AG-based envelope immunogens also generated potent binding antibodies, and one animal elicited antibodies that neutralized almost all (13 of 16, 81.3%) tier 2 HIV-1 isolates tested. Overall, the results suggest that the novel CRF02_AG-based envelope immunogens and prime-boost immunization strategy elicit the type of immune responses required for a preventive HIV-1 vaccine.
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