Andrew D. Redd, PhD, on Similar HIV Strains and Antibody Responses
During the late 1980s and early 1990s, Baltimore, Maryland, had experienced an increase in HIV cases. Some of affected individuals were registered in the 1988-1989 AIDS Linked to the IntraVenous Experience (ALIVE) cohort study.1 Now, results of a new genetic analysis2 of the ALIVE cohort show that some participants who had injected drugs and who had been newly infected with HIV upon study entry had been infected with highly similar viruses.
In all, 3 groups of individuals who were infected with highly similar virus strains were identified. According to the analysis authors, this finding suggests that the Baltimore-based individuals may have been part of transmission clusters.
The results also suggest that the infecting viral strain may have a small but significant effect on the resulting anti-HIV neutralizing antibody response and that individuals infected with similar viral strains can generate partially similar antibody responses.
Andrew D. Redd, PhD, from the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases Laboratory of Immunoregulation, is co-author of the analysis. Infectious Diseases Consultant asked Dr Redd about his findings and what they may mean for the future of an HIV vaccine.
INFECTIOUS DISEASES CONSULTANT: What knowledge gap were you hoping to bridge through this study?
Andrew Redd: A large study3 from Switzerland previously suggested that people who are infected with similar viral strains develop similar anti-HIV neutralizing antibody responses. The Swiss team determined that only about 10% of the HIV antibody response in an individual was attributable to the particular HIV genotype he or she acquired. To see if we could verify this finding, we looked at the link between neutralizing antibody development and viral linkage in a smaller, more detailed way by examining people who injected drugs who had recently acquired HIV.
ID CON: In what way is understanding/recognizing transmission clusters helpful for the treatment of patients with HIV?
AR: The viral genetic data suggested that these individuals were part of transmission clusters. Transmission cluster analysis is mainly helpful for determining how the virus is spreading in a community on a large scale. Understanding this can help to develop strategies to identify individuals who are most at risk for acquiring the virus and stopping the infection if possible.
Although our findings do not have direct clinical ramifications, I think they highlight the complexity of the immune response to HIV and are a reminder that every patient reacts to HIV in a slightly different way.
ID CON: How can these findings aid the development of a successful protective HIV vaccine?
AR: Our data support the Swiss team’s findings that a small part of a patient’s neutralizing antibody response to HIV is influenced by the viral variant he or she acquires. However, this is only a small factor in determining a given individual’s anti-HIV antibody response. Our data imply that vaccine constructs will need to be designed in such a way as to augment the natural variability found in each patient’s immune response to achieve a universal neutralization pattern in all vaccines.
ID CON: Based on your findings, what are your next steps?
AR: The next step is to examine which viral components contribute to different aspects of the neutralizing antibody response in order to determine the best constructs to use in a vaccine designed to recreate that immune response.
References:
- Johns Hopkins Bloomberg School of Public Health. AIDS Linked to the IntraVenous Experience (ALIVE). The ALIVE Study. https://www.jhsph.edu/research/affiliated-programs/aids-linked-to-the-intravenous-experience/.
- Redd AD, Doria-Rose NA, Weiner JA, et al. Longitudinal antibody responses in people who inject drugs infected with similar human immunodeficiency virus strains. J Infect Dis. 2020;221(5):756-765. https://doi.org/10.1093/infdis/jiz503.
- Kouyos RD, Rusert P, Kadelka C, et al; Swiss HIV Cohort Study. Tracing HIV-1 strains that imprint broadly neutralizing antibody responses. Nature. 2018;561(7723):406-410. doi:10.1038/s41586-018-0517-0.