Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.
A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
Duke Scholars
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- env Gene Products, Human Immunodeficiency Virus
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- SAIDS Vaccines
- Risk
- Phylogeny
- Molecular Sequence Data
- Male
- Macaca mulatta
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- env Gene Products, Human Immunodeficiency Virus
- Simian immunodeficiency virus
- Simian Immunodeficiency Virus
- Simian Acquired Immunodeficiency Syndrome
- SAIDS Vaccines
- Risk
- Phylogeny
- Molecular Sequence Data
- Male
- Macaca mulatta