Page 18 Adam • Evaluation of the Humoral/Fc-mediated Immune Responses… compared to the trivalent vaccine (p<0.05). This TRAVERSE study, however, did produce a few concerning results (Baden et al., 2020). What is rather disconcerting, is the fact that, although the tetravalent vaccine induced more IgG3 and IgG1 Abs, IgG3s were only detectable in 66-67% of participants, and no IgG1 response rates were provided. Further, slightly disconcerting, findings had to do with the elicited ADCP and ADCC responses. In terms of ADCP responses, the tetravalent group could induce significantly higher phagocytosis scores than the trivalent vaccine, but only against Clade A gp140 and Clade C gp140 - not against Clade B gp140. Additionally, although the ADCC response rates and ADCC percent killing did appear higher from the tetravalent vaccine, no statistical significance was achieved here. Also, despite the seemingly improved ADCC response rates of the tetravalent vaccine versus the trivalent vaccine, the induced ADCC response rates by the tetravalent vaccine were still no higher than 52%. Thus, although the tetravalent vaccine does begin to show significant improvements upon the trivalent vaccine in terms of eliciting important immune correlates of protection (particularly ADCP and IgG1/3), these correlates were by no means elicited uniformly among all the participants in the study (Baden et al., 2020). Thus, from Baden et al.’s findings, it must be asked whether or not this TRAVERSE study supports the idea of advancing an Ad26 viral vector/gp140 subunit vaccine regimen for HIV-1 into further clinical trials. Although Baden et al. did make a few concerning discoveries, it seems as though this TRAVERSE study further answers the question as to whether or not an Ad26- vectored/gp140 subunit regimen should be advanced into phase 2 clinical trials, by providing evidence that it should. From the APPROACH study, Barouch et al. had already determined that the older Ad26.Mos.HIV/gp140 subunit vaccine regimen should be, based on its protectiveness in macaques’ models, advanced to phase 2 clinical trials. Thus, since the newer Ad26.Mos4.HIV/gp140 subunit regimen elicits even greater total IgG Ab production - as well as, more specifically, greater IgG3 and IgG1 Ab production - in addition to a significantly improved Ab ability for recognition/binding to a larger spectrum of HIV-1 antigen variants, it seems as though the new tetravalent-based regimen should be advanced to phase 2 clinical trials as well - which is exactly what Baden et al. concluded at the end of this TRAVERSE study. This decision is supported by the fact that the new Ad26.Mos4.HIV vaccine was deemed just as safe and tolerable as the earlier Ad26.Mos.HIV vaccine. Thus, utilizing the newer tetravalent-based vaccine regimen would likely not prove harmful for recipients of the vaccine in the future - though it should be acknowledged that this TRAVERSE study did use both a smaller and less diverse sample size of participants. Additionally, although IgG3 Abs were not elicited in all patients by the tetravalent-based vaccine regimen, the response rates were certainly improved over the trivalent-based vaccine regimen (66% vs 46% at both vaccine regimen’s peak immunogenicity), which is necessary for advancing the development of a potentially useful, prophylactic vaccine
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