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Passively transferred antibodies directed against conserved regions of SIV envelope protect macaques from SIV
M G Lewis1, W R Elkins, F E McCutchan
1Henry M. Jackson Foundation Research Laboratory, Rockville, MD 20852.
Abstract:
Inactivated plasma collected from either SIV-infected or peptide-vaccinated macaques was transferred into 17 naive rhesus monkeys. Two additional macaques received normal plasma and served as controls. Following transfer all 19 monkeys were inoculated with SIV. While the controls became infected and were virus-isolation-positive, 3 of 6 recipients of SIV peptide vaccine plasma and 9 of 11 recipients of SIV-infected monkey plasma were protected. None of the 12 protected animals became virus-isolation-positive or seroconverted within 100 days of follow-up. One, however was SIV-PCR-positive. All 12 protected animals were rechallenged 100 days after the initial inoculation; 8 became infected and yielded virus as expected, but 4 remained uninfected. One of the latter was the SIV-PCR-positive monkey mentioned above, suggesting that cryptic SIV infection may be of significance in immunological protection. The results demonstrate that envelope anti-peptide antibodies have similar protective potential in vivo as antibodies directed to the whole virus. In vitro neutralization competition assays performed with sera from vaccinated macaques in the presence of the free peptides suggest that of the four conserved envelope peptides of the vaccine, the two originating from gp41 rather than the two from gp120 are responsible for inducing the neutralizing anti-syncytial activity.
Insights
Passive transfer of plasma from SIV-infected or peptide-vaccinated macaques protected naive monkeys against simian immunodeficiency virus (SIV) challenge. Antibodies targeting gp41 peptides were key to this protective immunity.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Passive antibody transfer is a strategy to confer temporary immunity.
- Understanding protective immune responses against simian immunodeficiency virus (SIV) is crucial for developing human immunodeficiency virus (HIV) vaccines.
Purpose of the Study:
- To evaluate the protective efficacy of plasma containing antibodies against SIV.
- To determine the specific viral targets responsible for induced protection.
Main Methods:
- Plasma transfer from SIV-infected or peptide-vaccinated macaques to naive recipients.
- SIV challenge inoculation of all macaques.
- Monitoring for viral load, seroconversion, and protection post-challenge.
- In vitro neutralization competition assays to identify key antigenic targets.
Main Results:
- Plasma recipients showed significant protection against SIV infection compared to controls.
- Protected animals did not seroconvert or become virus-isolation-positive initially, though some were SIV-PCR-positive.
- Rechallenge revealed durable protection in a subset of initially protected animals, suggesting cryptic infection.
- Antibodies targeting gp41 peptides were identified as crucial for in vitro neutralization.
Conclusions:
- Passive antibody transfer can confer protection against SIV infection.
- Antibodies targeting conserved envelope peptides, particularly from gp41, can induce protective immunity.
- The findings support the development of peptide-based vaccines targeting conserved regions of viral envelopes.