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Protection of rhesus macaques from SIV infection by immunization with different experimental SIV vaccines
P de Vries1, J L Heeney, J Boes
1Laboratory of Immunobiology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Abstract:
The immunogenicity and efficacy of an inactivated whole SIVmac (32H) preparation adjuvanted with muramyl dipeptide (SIV-MDP) and a gp120-enriched SIVmac (32H) ISCOM preparation (SIV-ISCOM), were compared by immunizing four rhesus macaques (Macaca mulatta) four times with SIV-MDP and four others in the same way with SIV-ISCOM. Two monkeys immunized with whole inactivated measles virus (MV) adjuvanted with MDP (MV-MDP) and two monkeys immunized with MV-ISCOM served as controls. In the SIV-ISCOM-immunized monkeys higher SIV-specific serum antibody titres were found than in the SIV-MDP-immunized monkeys. In contrast to the MV-immunized monkeys all SIV-MDP- and SIV-ISCOM-immunized monkeys were protected against intravenous challenge 2 weeks after the last immunization with 10 median monkey infectious doses (MID50) of a cell-free SIVmac (32H) challenge stock propagated in the human T-cell line C8166. After 43 weeks the protected monkeys were reboosted and 2 weeks later rechallenged with 10 MID50 of the same virus produced in peripheral blood mononuclear cells (PBMC) from a rhesus macaque. None of these animals proved to be protected against this challenge. In a parallel experiment in which the same numbers of monkeys were immunized in the same way, the animals were challenged intravenously with 10 MID50 of PBMC from an SIVmac (32H)-infected rhesus macaque. Two out of four SIV-MDP- and two out of four SIV-ISCOM-immunized monkeys proved to be protected from SIV infection.
Insights
Two SIV vaccine candidates, SIV-MDP and SIV-ISCOM, were tested in rhesus macaques. Both protected against initial challenge, but efficacy waned upon re-challenge with a different virus stock.
Area of Science:
- Veterinary Immunology
- Virology
- Vaccine Development
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a model for HIV research.
- Developing effective SIV vaccines is crucial for advancing human immunodeficiency virus (HIV) vaccine strategies.
- Assessing vaccine immunogenicity and efficacy requires rigorous challenge studies in relevant animal models.
Purpose of the Study:
- To compare the immunogenicity and efficacy of two SIVmac (32H) vaccine preparations: SIV-MDP and SIV-ISCOM.
- To evaluate the protective capacity of these vaccines against homologous and heterologous SIV challenges.
- To determine the durability of vaccine-induced protection over time.
Main Methods:
- Four rhesus macaques were immunized four times with SIV-MDP and four with SIV-ISCOM.
- Control groups received inactivated measles virus (MV) with MDP (MV-MDP) or MV-ISCOM.
- Monkeys were challenged intravenously with cell-free SIVmac (32H) or SIV derived from peripheral blood mononuclear cells (PBMC).
Main Results:
- SIV-ISCOM induced higher SIV-specific serum antibody titers than SIV-MDP.
- All SIV-vaccinated macaques were initially protected against a cell-free SIVmac challenge.
- Protection was not observed upon re-challenge with SIV propagated in PBMC; 2/4 in each vaccine group were protected in a parallel PBMC challenge experiment.
Conclusions:
- Both SIV-MDP and SIV-ISCOM demonstrated initial protective efficacy in rhesus macaques.
- Vaccine efficacy may be dependent on the challenge stock and potentially wanes over time.
- Further research is needed to develop vaccines conferring durable protection against diverse SIV challenges.