Abstract

ABSTRACTA 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 with a panel of HIV-1 envelope (Env) gp140 protein immunogens over a period of 200 weeks in guinea pigs. We assessed vaccine regimens that included a monovalent clade C gp140 (C97ZA012 [C97]), a tetravalent regimen consisting of four clade C gp140s (C97ZA012, 459C, 405C, and 939C [4C]), and a tetravalent regimen consisting of clade A, B, C, and mosaic gp140s (92UG037, PVO.4, C97ZA012, and Mosaic 3.1, respectively [ABCM]). We found that the 4C and ABCM prime/boost regimens were capable of eliciting greater magnitude and breadth of binding antibody responses targeting variable loop 2 (V2) over time than the monovalent C97-only regimen. The longitudinal boosting regimen conducted over more than 2 years increased the magnitude of certain tier 1 NAb responses but did not increase the magnitude or breadth of heterologous tier 2 NAb responses. These data suggest that additional immunogen design strategies are needed to induce broad, high-titer tier 2 NAb responses.IMPORTANCE 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 different immunogens to determine if we could elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than 2 years increased tier 1 NAb responses but did not increase the magnitude and breadth of tier 2 NAb responses. These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses.

Highlights

  • A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies remains an unachieved goal of the HIV-1 vaccine field

  • We evaluated the effects of a longitudinal prime/boost vaccination regimen on the evolution of binding and NAb responses in guinea pigs over a vaccination regimen that spanned more than 2 years

  • We evaluated whether repeated boosting with homologous or heterologous gp140 Env immunogens over a prolonged period of time would increase the magnitude and breadth of NAb responses

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Summary

Introduction

A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. The longitudinal boosting regimen conducted over more than 2 years increased the magnitude of certain tier 1 NAb responses but did not increase the magnitude or breadth of heterologous tier 2 NAb responses These data suggest that additional immunogen design strategies are needed to induce broad, high-titer tier 2 NAb responses. We found that longitudinal boosting over more than 2 years increased tier 1 NAb responses but did not increase the magnitude and breadth of tier 2 NAb responses These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses. While we observed a limited breadth of tier 2 NAbs in all vaccination regimens, the breadth and magnitude of these NAbs did not increase over the course of the longitudinal regimen These data suggest that novel immunogen design strategies and vaccination regimens will be needed to improve tier 2 NAb responses

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