Channels • 2022 • Volume 6 • Number 2 Page 19 regimen. Furthermore, though ADCC % killing values weren’t significantly higher in response to the tetravalent vaccine regimen, the ADCP scores were significantly higher against some tested antigens. This discrepancy, however, should - perhaps - be an expected result. Additional studies into the contributions of ADCP and ADCC in combating HIV-1 infection have suggested that ADCP contributes significantly more to fighting the virus than ADCC (Sips et al., 2016). Thus, there is precedence then, while still acknowledging the lack of significance in ADCC % killings, to focus more heavily on the improvements in ADCP scores. If this viewpoint is presumed, then the tetravalent regimen demonstrates an even more impressive improvement upon the trivalent regimen (since Clade C-specific and Clade A-specific ADCP responses were significantly higher in the tetravalent group). What’s truly fascinating, however, is the fact that not only did Baden et al. provide evidence that the Ad26.Mos4.HIV vaccine would be more effective in eliciting immune correlates of protection than the Ad26.Mos.HIV vaccine, it seems as though the researchers in charge of the ongoing Imbokodo study (a phase 2 trial) have replaced the trivalent Ad26.Mos.HIV vaccine with the newer, tetravalent Ad26.Mos4.HIV vaccine. At the end of the APPROACH study, Barouch et al. mention that the Imbokodo study was being initiated based on state- of-the-art, at the time, Ad26.Mos.HIV vaccine. However, when reading over the end of the TRAVERSE study, Baden et al. mention that the ongoing Imbokodo study is utilizing the newer Ad26.Mos4.HIV vaccine (Baden et al., 2020; Barouch et al., 2018). Upon further examination of this seeming contradiction, one finds on ClinicalTrials.gov that the Ad26.Mos.HIV vaccine is not mentioned in the intervention/treatment section. In fact, only the Ad26.Mos4.HIV vaccine is mentioned alongside the gp140 subunit vaccine (Janssen Vaccines & Prevention B.V., 2020). Therefore, it seems as though Barouch et al. replaced the Ad26.Mos.HIV vaccine with the Ad26.Mos4.HIV vaccine shortly after discovering the improved capabilities of the new tetravalent vaccine during the TRAVERSE trial. Evidently then, Baden et al. found the Ad26.Mos4.HIV/gp140 subunit regimen so convincing that they were willing to replace their older, successful vaccine with it in not just the phase 2 Imbokodo study, but also initiate another phase 2 clinical study called MOSAICO using the tetravalent vaccine exclusively (Baden et al., 2020). The TRAVERSE study, however, still doesn’t answer a few key questions. First, the TRAVERSE study, like the APPROACH study, doesn’t elucidate whether or not the rhesus macaque model with SHIV challenge is a reliable basis for predicting the protection of a particular HIV-1 vaccine regimen in humans. In addition to this, this TRAVERSE also doesn’t answer whether it is the quantity of Fc-mediated effector functions and Fc- mediating Abs that are the best predictors of protection against HIV-1 acquisition, or if it is more-so the quality (increased cooperation/correlation) of Fc-mediated effector functions that best predict protection against acquiring HIV-1. Hopefully, with the conclusion of the MOSAICO and
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