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HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.

HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
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McCurley NP, Domi A, Basu R, Saunders KO, LaBranche CC, Montefiori DC, Haynes BF, Robinson HL,


McCurley NP, Domi A, Basu R, Saunders KO, LaBranche CC, Montefiori DC, Haynes BF, Robinson HL, (click to view)

McCurley NP, Domi A, Basu R, Saunders KO, LaBranche CC, Montefiori DC, Haynes BF, Robinson HL,

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PloS one 2017 10 1112(10) e0177863 doi 10.1371/journal.pone.0177863

Abstract

Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.

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