Channels, Spring 2022

Channels • 2022 • Volume 6 • Number 2 Page 17 (33 people). In terms of the regimens/doses of vaccines utilized, these were identical to the Ad26/Ad26 HD gp140 regimen from the APPROACH study, except for the fact that the tetravalent group had the new tetravalent Ad26.Mos4.HIV vaccine, but the trivalent group had the trivalent Ad26.Mos.HIV vaccine. As such, both the tetravalent and trivalent vaccines were given at a dose of 5x10^10 vp/0.5mL, and the gp140 subunit booster vaccines were given at the same dose as the APPROACH study - 250µg of gp140 with 0.425mg of Alum adjuvant. Likewise, the placebo group got 0.9% saline solution. In terms of the injection schedule, two Ad26 vector priming vaccines (either tetravalent or trivalent) were given at weeks 0 (beginning) and 12. Then at weeks 24 and 48, the boosting Ad26 vector vaccines were also accompanied by the gp140 booster vaccines. Of course, the placebo group followed the same injection schedule but with the saline vaccines. Finally, blood serum was taken from each of the participants 4 weeks after the second, third and fourth vaccinations (as well as 6 months after the fourth vaccination) in order to calculate the humoral and cellular immune responses elicited. (Baden et al., 2020; Barouch et al., 2018). Now, after discussing how Baden et al. conducted their research, it is important to discuss the results of Baden et al.’s TRAVERSE study. The overall discovery of the TRAVERSE study was that the vaccine regimen that included the tetravalent Ad26 vaccine (Ad26.Mos4.HIV) appeared significantly more immunogenic than the vaccine regimen with only the trivalent Ad26 vaccine (Ad26.Mos.HIV). First, as determined by ELISA, in overall IgG Ab production (specific to a Clade A, a Clade B, and two Clade C gp140 antigens), the tetravalent group demonstrated higher titers than the trivalent group at each of the four serum draws. For this study, unlike in the APPROACH study, statistical analyses were conducted between the titer values on the total IgG ELISAs, thereby demonstrating that the higher titers produced in response to the tetravalent vaccine were statistically significant (p<0.05). Specifically, at both the tetravalent and trivalent-based vaccine regimens’ most immunogenic (serum draw four weeks after fourth vaccination) the tetravalent group produced, on average, around three-fold higher titers of total IgG Abs then the trivalent group did. Additionally, when looking at longer-term total IgG titers, the tetravalent group demonstrated more than two-fold higher IgG titers than the trivalent group. Another really important finding from this study, was that when Baden et al. ran three BAMAs (Binding Antibody Multiplex Assays) - one with 9 gp140 variants as antigens, one with 20 gp120 variants as antigens, and one with 16 gp70 V1V2 variants as antigens - the tetravalent vaccine demonstrated significantly higher binding breadth (post- third vaccination, post-fourth vaccination, and post 6 months after fourth vaccination) compared to the trivalent vaccine (p<0.0001). This finding is critical, since one of the needed characteristics of a universal, prophylactic HIV-1 vaccine would be an ability to elicit immune responses that are able to recognize (and build immunological memory against) an increasingly broader spectrum of possible HIV-1 antigen variants. Additionally, when analyzing the relative titers of specifically IgG1 and IgG3 Abs produced between the groups, the tetravalent vaccine elicited significantly higher titers, at all tested serum draws,

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