HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
| Autor: | Nathanael P McCurley, Arban Domi, Rahul Basu, Kevin O Saunders, Celia C LaBranche, David C Montefiori, Barton F Haynes, Harriet L Robinson |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | PLoS ONE, Vol 12, Iss 10, p e0177863 (2017) |
| Druh dokumentu: | article |
| ISSN: | 1932-6203 71696571 |
| DOI: | 10.1371/journal.pone.0177863 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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