Related Experiment Videos
Live, attenuated simian immunodeficiency virus vaccines elicit potent resistance against a challenge with a human
R Shibata1, C Siemon, S C Czajak
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Abstract:
Three rhesus macaques, previously immunized with SIVdelta3 or SIVdelta2, each an attenuated derivative of SIVmac239, and two naive monkeys were challenged with 30,000 50% tissue culture infective doses of SHIV, an SIV/human immunodeficiency virus type 1 (HIV-1) chimeric virus bearing the dual-tropic envelope of HIV-1DH12. By several criteria, including virus isolation, serological assays, and PCR (both DNA and reverse transcriptase), SHIV levels were reduced to barely detectable levels in the circulating blood of vaccinated animals. The resistant SIV-vaccinated macaques had no preexisting neutralizing antibodies directed against SHIV, nor did they produce neutralizing antibodies at any time over a 14-month observation period following SHIV challenge. Interestingly, SIV sequences, derived from the vaccine, could be amplified from numerous tissue samples collected at the conclusion of the experiment, 60 weeks postchallenge, but SHIV-specific sequences (viz., HIV-1 env) could not. These results demonstrate that live attenuated SIV vaccines provide strong long-term protection even against challenge strains with highly divergent envelope sequences.
Insights
Live attenuated simian immunodeficiency virus (SIV) vaccines protected macaques against a simian-human immunodeficiency virus (SHIV) challenge. This long-term protection occurred despite divergent envelope sequences and lack of neutralizing antibodies.
Area of Science:
- * Virology
- * Immunology
- * Vaccine Development
Background:
- * Simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) share similarities, making SIV a model for HIV-1 research.
- * Attenuated SIV vaccines are being explored for their potential to induce protective immunity against SIV and HIV-1.
- * Chimeric viruses like SHIV (SIV/HIV-1) are used to model HIV-1 infection and assess vaccine efficacy.
Purpose of the Study:
- * To evaluate the long-term protective efficacy of live attenuated SIV vaccines against a heterologous SHIV challenge.
- * To investigate the immune responses, including neutralizing antibodies, in vaccinated macaques post-challenge.
- * To determine the persistence of vaccine-derived SIV and the absence of challenge SHIV in vaccinated animals.
Main Methods:
- * Three rhesus macaques vaccinated with attenuated SIV (SIVdelta3 or SIVdelta2) and two naive macaques were challenged with SHIV-111.258 (HIV-1DH12 envelope).
- * Viral loads were assessed using virus isolation, serological assays, and PCR (DNA and RT-PCR).
- * Neutralizing antibody responses were measured, and tissue samples were analyzed for SIV and SHIV sequences post-mortem.
Main Results:
- * Vaccinated macaques exhibited significantly reduced SHIV levels, often below detectable limits, in circulating blood.
- * No pre-existing or induced neutralizing antibodies against SHIV were detected in the resistant vaccinated animals.
- * SIV vaccine sequences were found in multiple tissues 60 weeks post-challenge, while SHIV-specific sequences (HIV-1 env) were absent.
Conclusions:
- * Live attenuated SIV vaccines confer strong, durable protection against heterologous SHIV challenge.
- * Protection is achieved independently of neutralizing antibodies against the challenge virus.
- * The persistence of vaccine-derived SIV may contribute to long-term protection against divergent viral strains.