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Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs.

Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs.
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Bricault CA, Kovacs JM, Badamchi-Zadeh A, McKee K, Shields JL, Gunn BM, Neubauer GH, Ghantous F, Jennings J, Gillis L, Perry J, Nkolola JP, Alter G, Chen B, Stephenson KE, Doria-Rose N, Mascola JR, Seaman MS, Barouch DH,


Bricault CA, Kovacs JM, Badamchi-Zadeh A, McKee K, Shields JL, Gunn BM, Neubauer GH, Ghantous F, Jennings J, Gillis L, Perry J, Nkolola JP, Alter G, Chen B, Stephenson KE, Doria-Rose N, Mascola JR, Seaman MS, Barouch DH, (click to view)

Bricault CA, Kovacs JM, Badamchi-Zadeh A, McKee K, Shields JL, Gunn BM, Neubauer GH, Ghantous F, Jennings J, Gillis L, Perry J, Nkolola JP, Alter G, Chen B, Stephenson KE, Doria-Rose N, Mascola JR, Seaman MS, Barouch DH,

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Journal of virology 2018 04 11() pii JVI.00369-18
Abstract

A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here we report the immunogenicity of longitudinal prime/boost vaccination regimens over a period of 200 weeks in guinea pigs with a panel of HIV-1 envelope (Env) gp140 protein immunogens. We assessed vaccine regimens that included a monovalent clade C gp140 regimen (C97), a tetravalent regimen consisting of four clade C gp140s (4C), and a tetravalent regimen consisting of a clade A, B, C, and mosaic gp140 (ABCM). We found that the 4C and ABCM prime/boost regimens were capable of eliciting a greater magnitude and breadth of binding antibodies targeting variable loop 2 (V2) over time, compared to the monovalent C97 only regimen. The longitudinal boosting regimen conducted over more than two years increased the magnitude of certain tier 1 NAbs, but did not increase the magnitude or breadth of heterologous tier 2 NAbs. These data suggest that additional immunogen design strategies are needed to induce broad, high titer tier 2 NAbs. The elicitation of potent, broadly neutralizing antibodies (bNAbs) remains an elusive goal for the HIV-1 vaccine field. In this study we explored the use of a long-term vaccination regimen with differing immunogens to determine if we could elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than two years increased tier 1 NAbs but did not increase the magnitude and breadth of tier 2 NAbs. These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses.

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