Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques.

Abstract:

:An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mutations that can partially restore the fitness cost of immune-evading mutations. Based on the fitness landscapes of HIV proteins that account for the effects of coupled mutations, we designed a single long peptide immunogen comprising parts of the HIV proteome wherein mutations are likely to be deleterious regardless of the sequence of the rest of the viral protein. This immunogen was then stably expressed in adenovirus vectors that are currently in clinical development. Macaques immunized with these vaccine constructs exhibited T-cell responses that were comparable in magnitude to animals immunized with adenovirus vectors with whole HIV protein inserts. Moreover, the T-cell responses in immunized macaques strongly targeted regions contained in our immunogen. These results suggest that further studies aimed toward using our vaccine construct for HIV prophylaxis and cure are warranted.

authors

Murakowski DK,Barton JP,Peter L,Chandrashekar A,Bondzie E,Gao A,Barouch DH,Chakraborty AK

doi

10.1073/pnas.2022496118

subject

Has Abstract

pub_date

2021-02-02 00:00:00

issue

5

eissn

0027-8424

issn

1091-6490

pii

2022496118

journal_volume

118

pub_type

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