A new HIV vaccine candidate shows promise in female macaques
The vaccine candidate, called ALVAC-SIV/gp120, is based on a recombinant canarypox virus expressing SIV antigens and a recombinant gp120 protein. The researchers tested the vaccine in 36 female macaques that were challenged intravaginally with repeated doses of SIVmac251, a highly pathogenic strain of simian immunodeficiency virus (SIV).
The results showed that the vaccine conferred 83% protection against SIV acquisition, with only three out of 18 vaccinated macaques becoming infected after 12 challenges. The vaccine also reduced the viral load and preserved the CD4+ T cells in the infected macaques.
The researchers revealed that the vaccine induced two key immune mechanisms that contributed to its efficacy: efferocytosis and antibody-dependent cellular cytotoxicity (ADCC). Efferocytosis is the process of clearing apoptotic cells by phagocytes, which reduces inflammation and maintains tissue homeostasis. ADCC is the process of killing infected cells by natural killer cells, which are activated by antibodies binding to viral antigens.
The researchers found that the vaccine stimulated efferocytosis by increasing the expression of CCL2 and CCR2, two molecules involved in recruiting monocytes to the site of infection. The vaccine also enhanced ADCC by inducing antibodies that recognized a specific region of gp120 called V2. These antibodies were able to bind to infected cells and trigger their elimination by natural killer cells.
The researchers concluded that their study provides new insights into the immune correlates of protection for HIV vaccines and suggests that efferocytosis and V2-specific ADCC are important factors for preventing HIV acquisition.
Why is this study important?
HIV is a global health threat that affects millions of people worldwide. Despite decades of research, there is still no effective vaccine to prevent HIV infection. Current vaccine candidates have shown limited or no efficacy in clinical trials, partly due to the high genetic diversity and immune evasion strategies of HIV.
Therefore, there is an urgent need to develop new vaccine candidates that can elicit potent and durable immune responses against diverse HIV strains. Animal models, such as macaques infected with SIV, are useful tools to evaluate the potential of new vaccine candidates and to understand the mechanisms of protection.
The study by Bissa et al. is one of the first to demonstrate a high level of protection against SIV acquisition in female macaques using a recombinant canarypox virus-based vaccine. This vaccine platform has several advantages, such as safety, stability, and ability to express multiple antigens.
Moreover, the study reveals novel immune mechanisms that mediate vaccine efficacy, such as efferocytosis and V2-specific ADCC. These mechanisms have not been previously reported for HIV vaccines and may have implications for vaccine design and evaluation.
What are the limitations and future directions?
The study by Bissa et al. has some limitations that need to be addressed in future research. First, the study used a single SIV strain (SIVmac251) to challenge the macaques, which may not represent the diversity and complexity of HIV strains circulating in humans. Therefore, it is unclear whether the vaccine would be effective against other SIV or HIV strains.
Second, the study did not investigate the long-term durability and memory of the immune responses induced by the vaccine. It is possible that the immune responses may wane over time or be affected by environmental factors, such as co-infections or hormonal changes. Therefore, it is important to monitor the immune responses and protection levels over longer periods of time and under different conditions.
Third, the study did not explore the role of other immune cells or molecules that may be involved in vaccine efficacy, such as T cells, B cells, cytokines, or chemokines. It is possible that these factors may modulate or synergize with efferocytosis and ADCC to enhance or impair vaccine efficacy. Therefore, it is necessary to perform a comprehensive analysis of the immune system after vaccination and challenge.
Finally, the study did not test the vaccine in humans, which is the ultimate goal of HIV vaccine research. It is possible that there may be differences in immunogenicity, safety, or efficacy between macaques and humans due to genetic or physiological factors. Therefore, it is essential to conduct clinical trials to evaluate the safety and efficacy of the vaccine in humans.
1: Bissa M, Kim S, Galli V, et al. HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC. Nat Commun. 2023;14(1):575. doi:10.1038/s41467-023-36109-8