Page 14 Adam • Evaluation of the Humoral/Fc-mediated Immune Responses… responses elicited (of which, ADCP and IgG production will be discussed.) The same vaccine groups were then administered to 72 rhesus macaques (12 in each group), minus the low dose option for gp140 subunit booster, which were then challenged with SHIV to determine the protective effects of each of the vaccine groups against SHIV infection as a model of protection for each vaccine regimen in humans (Barouch et al., 2018). Having now discussed the methods that Barouch et al. used, it’s important to take a brief look at what Barouch et al. found from this overarching study. From the APPROACH study, Barouch et al. noticed that the inclusion and dosage of the gp140 subunit booster did seem to increase the titers of total Abs (measured by ELISA) produced that targeted Clade C gp140. Furthermore, the inclusion of a viral vector vaccine booster also seemed to increase total titers of Ab’s specific to Clade C gp140. The caveat with these observations, however, is the fact that Barouch et al. didn’t conduct any formal statistical analyses (particularly t-tests) between the titer values of overall Ab’s produced against the Clade C gp140. Therefore, Barouch et al. were merely capable of only looking at apparent, non-statistically significant trends in total Ab production. This was also the case when Barouch et al. were using ELISAs to look at the relative quantities of specifically IgGs produced against Clade A, B, and C gp140 antigens by each regimen, when looking at which IgG subtypes were most prevalent against Clade C gp140, and when looking at which regimen produced the most ADCP activity. Therefore, there was no evidence provided to demonstrate that the null hypothesis (in this case that two groups being compared had the same titer of Abs produced, same titers of total IgG Abs produced, same IgG subtypes produced, or same amount of ADCP induced) could be disproven. In fact, the only statistically significant data provided by Barouch et al., was a linear regression graph that demonstrated (with an r of 0.6957 and a p-value of <0.0001) that the ADCP activity and the Clade C specific Ab titers (which were shown - though without statistical significance - to be primarily IgG1 and IgG3) were strongly correlated. From this piece of statistically significant data, however, and despite the lack of statistical significance in the ELISAs, it could still be argued that Barouch et al.’s vaccine regimens did accomplish the goal of eliciting the currently-understood immune correlates of protection against HIV-1 infection (IgG Ab production with accompanying Fc-mediated effector functions). For example, it could be reasoned that the missing p-values, for the differences between the titers of Abs produced and ADCP observed, isn’t harmful to the impact of the overarching study, due to one particularly important finding from the concurrent rhesus monkey study. Since Barouch et al. were able to conduct the same experiment in rhesus monkeys (though at a smaller sample size of 72), they were able to directly see how well the different vaccine regimens protected against viral infection by attempting to infect the rhesus macaques with SHIV (a very similar virus to HIV-1) six separate times. What they found, was that out of the 12 macaques injected with the Ad26 prime-Ad26/gp140 boost (Ad26/Ad26 HD gp140) regimen, and subsequently challenged with SHIV, 8 (67%) of them remained uninfected after the sixth challenge (p-value = 0.007). This was higher than the second most effective regimen (the Ad26 prime-MVA/gp140 boost regimen). It was then from this data, along
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