Page 20 Adam • Evaluation of the Humoral/Fc-mediated Immune Responses… Imbokodo studies, these - and other important questions - will be at least partially answered. Conclusion After evaluating the APPROACH and TRAVERSE studies, particular pieces of data must be reiterated that demonstrate the advancement of an Ad26-vectored/gp140 subunit HIV-1 vaccine regimen, past phase 1/2a testing, is warranted. In doing this, the APPROACH and TRAVERSE trials clearly answer the question of this paper, put forth at the beginning of this analysis section, asking whether or not an Ad26-vector/gp140 subunit vaccine regimen could adequately elicit immune correlates of protection against HIV-1 to warrant further testing past phase 1/2a clinical trials. First, the APPROACH study (as the first phase 1/2a trial in which a non-prototype, Ad26-vectored was tested vaccine was tested) helped to demonstrate that an Ad26 vector-based prophylactic vaccine regimen can be safe, while also eliciting key immune correlates of protection that warrant its further investigation into phase 2 clinical trials. More specifically, however, the APPROACH study demonstrated that the most optimal regimen is a regimen incorporating two Ad26-vectored priming vaccinations, along with Ad26-vectored and gp140 subunit (high dose) booster vaccinations. Though the validity of the current infection model is still uncertain, this decision on the optimal regimen was determined via the protection of the regimen in rhesus macaques (Barouch et al., 2018). Then, following the APPROACH study, the TRAVERSE study demonstrated that the successful vaccine regimen from the APPROACH study could be further improved by increasing the valency of the Ad26-vectored component of the APPROACH regimen. Specifically, the new tetravalent component elicited increased magnitudes of key immune correlates of infection, further cementing the idea of advancing an Ad26 vector-based regimen - based on the knowledge that inclusion of additional mosaic antigens appears to reliably increase the breadth and quantity of immune correlates of protection, yet without increasing the side-effects of the vaccination (Baden et al., 2020). In addition to these aforementioned, critical pieces of evidence, remaining, unanswered questions were also touched on in the analysis section. Therefore, a brief discussion on future research that should occur to answer these, and other questions, seems appropriate.
RkJQdWJsaXNoZXIy MTM4ODY=