Department/School of the Primary Author
Science and Mathematics
Keywords
HIV, viral vectors, vaccine
DOI
10.15385/jch.2022.6.2.1
Abstract
Background and Introduction: HIV is one of the most problematic pandemics to date, currently infecting upwards of 38 million people worldwide (“The Global HIV/AIDS Epidemic,” 2020). Although infection and mortality rates have generally decreased, current prophylactic (preventive) measures against HIV-1 acquisition have shown major weaknesses that could be remedied with a vaccine (Pitisuttuthum & Marovich, 2020). Manufacturing an effective, prophylactic HIV-1 vaccine, however, is not without challenges - namely design/selection of vaccine-delivered immunogens (antigens) and elicitation of proper immune responses to HIV-1 antigens (Ng’uni et al., 2020). Fortunately, despite past, unsuccessful research, studies within the past 10-15 years have begun to elucidate immune correlates of protection against HIV-1 acquisition, specifically IgG1/IgG3 antibody (Ab) production, as well as non-neutralizing, Fc-Mediated effector functions (Rerks-Ngarm et al., 2009). Excitingly, studies released in the last 3 years, which use Adenovirus serotype-26 (Ad26) vector (Custers et al., 2020) show promising signs that an effective HIV-1 vaccine could become a reality (Baden et al., 2020; Barouch et al., 2018). Thus, for this presentation, I hope to show that Johnson & Johnson’s two new Ad26-based vaccines (combined with booster vaccines) sufficiently elicit key immune correlates of protection to warrant an Ad26 vector-based regimen’s testing past Phase 1/2a clinical trials. Results and Conclusions: Recent studies that demonstrate the abilities of an Ad26-based vaccine regimen to elicit key immune correlates of protection (while remaining generally safe) are the APPROACH and TRAVERSE studies. From the APPROACH study, it’s demonstrated that a regimen consisting of two Ad26 priming injections, followed by two Ad26 boosting injections and two subunit boosting injections (Ad26/Ad26 + HD gp140), elicits more IgG1/IgG3 Abs and ADCP (antibody-dependent cellular phagocytosis) when compared to six alternative candidate regimens. Additionally, when this Ad26/Ad26 + HD gp140 regimen was administered to rhesus macaques, a 94% reduction in disease acquisition was observed (Barouch et al., 2018). Building off of the APPROACH study, the TRAVERSE study demonstrates the effects on immunogenicity when the Ad26 vector’s valency is increased. Increase in valency resulted in increased IgG1/IgG3 Ab production, as well as increased phagocytosis.. Promisingly, the breadth of HIV-1 antigens recognized by IgG1/IgG3 Abs also increased when vaccine valency increased as well (Baden et al., 2020). From the results of these two studies then, and the researchers’ conclusions from them, it seems appropriate to advance these two new Ad26-based regimens into further clinical trials (Phase 2 and 3).
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Recommended Citation
Adam, Nathan E.
(2022)
"Evaluation of the Humoral/Fc-mediated Immune Responses to an Adenovirus-26 Viral Vector/gp140 Subunit Combined Vaccine Regimen as a Prophylactic HIV-1,"
Channels: Where Disciplines Meet: Vol. 6:
No.
2, Article 1.
DOI: 10.15385/jch.2022.6.2.1
Available at:
https://digitalcommons.cedarville.edu/channels/vol6/iss2/1