Three-dimensional X-ray crystallographic image showing the broadly neutralizing antibody B12 (green ribbon) in contact with a critical target (yellow) for vaccine developers on HIV-1 gp120 (red). Image credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health (CC BY-NC 2.0)
Viruses are genetic particles composed of DNA or RNA, encased by a protective protein shell called the capsid. They cannot reproduce independently and must infect a host cell to replicate. Many viruses mutate rapidly, allowing them to adapt to and evade the immune responses of their hosts.
For example, HIV-1, the virus that causes AIDS, has a high mutation rate, resulting in the emergence of many distinct variants of the virus. Therefore, an effective vaccine needs to be able to stimulate a special type of antibody known as broadly neutralizing antibody (bnAb). These large defense proteins can recognize and neutralize many different viral strains, which could make them a key focus in HIV vaccine development.
Researchers often use rhesus macaques as a model system to study how HIV-1 evolves and interacts with the immune system. Previous studies have shown that some viruses mutate in similar ways in both humans and rhesus macaques. However, the details of HIV-1 evolution and mutation patterns in these two hosts remain unclear. Gaining deeper insight into the evolutionary processes linked to bnAb development could inform vaccine design and evaluate the suitability of rhesus macaques as an animal model for HIV-1 research.
Shimagaki et al. aimed to quantify how HIV-1 evolves in different hosts and whether these evolutionary patterns differ between individuals who do or do not develop bnAbs. The researchers reanalyzed previously collected HIV-1 data from two humans who developed bnAbs and 13 rhesus macaques, using computational models to estimate how various mutations affect viral replication (i.e., viral fitness). Their analysis revealed strong quantitative similarities in viral evolution between humans and macaques: the estimated fitness effects of mutations were highly correlated across species. Rapid increases in viral fitness were observed before bnAbs were detected, suggesting that selective pressure on the virus may help drive the development of antibody breadth.
These findings suggest that vaccine strategies designed to replicate the conditions that lead to rapid viral adaptation may help stimulate broadly neutralizing antibody responses. The observed parallels in HIV-1 evolution between humans and rhesus macaques also support the continued use of macaques as a relevant model for HIV-1 research. Still, significant challenges remain. Future studies should explore the link between viral evolution and antibody development in larger cohorts. Moreover, vaccine development requires addressing many practical aspects – such as antigen selection and dosing regimens – which extend beyond the viral fitness dynamics explored in this study.
