Related Experiment Videos
Protection against mucosal SIVsm challenge in macaques infected with a chimeric SIV that expresses HIV type 1
M Quesada-Rolander1, B Mäkitalo, R Thorstensson
1Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden.
Abstract:
In a monkey model we used a chimeric SIV expressing the HIV-1 envelope gene (SHIV-4) as a live attenuated vaccine and a virulent SIVsm as a mucosal challenge. Four cynomolgus monkeys were inoculated intravenously with SHIV-4. Virus was repeatedly isolated from blood mononuclear cells of all four animals for 2 to 7 months after the inoculation of SHIV. All monkeys developed neutralizing antibodies to HIV-1 and high antibody titers to HIV-1 envelope glycoproteins. In contrast, no neutralizing antibodies to SIVsm were detected and cross-reacting antibodies to SIV envelope glycoproteins were demonstrable in low titers. Nine to 12 months after the SHIV inoculation the four monkeys and six naive control monkeys were challenged intrarectally with 10 monkey infectious doses of macaque cell-grown SIVsm. After a follow-up period of 1 year, two of four SHIV-infected monkeys were completely protected against SIVsm infection as shown by repeated negative virus isolations and negative polymerase chain reaction for SIV envelope DNA. One naive monkey that received blood from the two protected monkeys showed no signs of infection. The remaining two SHIV-infected monkeys showed an initial infection on challenge with SIVsm, but viral replication was thereafter suppressed. Cytotoxic T lymphocytes to SIV Nef and RT were demonstrable in one of four SHIV-infected monkeys before SIVsm challenge, but this monkey was not protected against SIV infection. All six control animals yielded virus repeatedly after SIVsm challenge and three of them showed declining CD4 cell counts. Thus, infection with SHIV expressing HIV-1 envelope could induce cross-protection against mucosal SIVsm challenge.
Insights
A chimeric simian-immunodeficiency virus (SIV) expressing the human immunodeficiency virus type 1 (HIV-1) envelope induced cross-protection against mucosal SIV challenge in monkeys. This live attenuated vaccine approach shows promise for future vaccine development.
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 relevant model for studying HIV-1 infection and vaccine strategies.
- * Live attenuated vaccines, such as chimeric SIV expressing HIV-1 envelope (SHIV-4), are being explored for their potential to induce robust immune responses and protection.
Purpose of the Study:
- * To evaluate the efficacy of a live attenuated SHIV-4 vaccine in conferring protection against a virulent SIVsm mucosal challenge in a cynomolgus monkey model.
- * To assess the immune responses, including antibody and cytotoxic T lymphocyte (CTL) generation, induced by SHIV-4 vaccination.
Main Methods:
- * Four cynomolgus monkeys were intravenously inoculated with SHIV-4 and monitored for viral shedding and antibody production.
- * Following vaccination, monkeys were intrarectally challenged with SIVsm, along with six naive control monkeys.
- * Protection was assessed through repeated virus isolation, polymerase chain reaction (PCR) for viral DNA, and monitoring of CD4 cell counts.
Main Results:
- * SHIV-4 infected monkeys developed neutralizing antibodies to HIV-1 and high titers to HIV-1 envelope glycoproteins.
- * Two of four vaccinated monkeys were completely protected against SIVsm challenge, showing no detectable virus or DNA.
- * The remaining two vaccinated monkeys experienced transient infection with suppressed viral replication, while all control animals became infected.
Conclusions:
- * Infection with SHIV-4 can induce significant cross-protection against SIVsm mucosal challenge in monkeys.
- * The study demonstrates the potential of live attenuated chimeric vaccines in eliciting protective immunity against lentiviral infections.
- * Further research into SHIV-based vaccines could offer a viable strategy for preventing HIV-1 transmission.