Channels, Spring 2022

Channels • 2022 • Volume 6 • Number 2 Page 11 Since live-attenuated and inactivated vaccine strategies have been deemed too risky to pursue as a basis for a prophylactic HIV-1 vaccine, another strategy must be implemented instead. The vaccine strategy that has proven to be safe and most effective in attempting to elicit an immune response to HIV-1 is the viral vector-based vaccine strategy. In fact, this was the strategy that was employed in the RV144 trial, which utilized a recombinant canarypox based vaccine (Ng’uni et al., 2020). Despite the moderate success of the canarypox vector, the viral vector that has been studied, and utilized, most recently is Adenovirus serotype-26 virus (Ad26). Ad26 is a DNA virus from the Adenoviridae family and was first identified back in 1956. What is particularly helpful about this serotype of adenovirus, is the fact that it is far less common than other serotypes of Adenoviruses, such as the far more common Ad5. This fact is important, since it means that people are less likely to already have immunological memory against Ad26, thereby preventing the body from destroying the Ad26 viral vector before it can deliver its immunogenic, transgenic cargo (Custers et al., 2020; Vrba et al., 2020). What’s even more fascinating, is the fact that studies, such one conducted by Baden et al. in 2013, demonstrated two important findings about the Ad26 vector they were testing. First, they determined that the Ad26 vector was immunogenic without the need of an accompanying adjuvant. Secondly, and most importantly, Baden et al. discovered that although participants’ bodies not only made Abs specific to the HIV-1 antigens the Ad26 vectors were expressing, but also increasingly against the Ad26 vectors, results did not appear to demonstrate that the increase in Ad26-specific Abs interfered noticeably with the titers of HIV-1-specific Abs that were also being produced. Therefore, it was shown that when the body is exposed to an Ad26 vector, it will produce an immune response to both the vector and the expressed antigens, however, the immune response’s focus on the vector doesn’t seem to prevent the vector from completing its goal of building immunological memory against the HIV-1 antigens (Baden et al., 2013). Despite the apparent effectiveness of the Ad26 viral vector, however, it should also be mentioned that the vector vaccines are also usually accompanied by subunit-based vaccines that are given as part of the booster portion of the regimen as well. Although the subunits included in these vaccines tended to be gp120 monomers in the past, an increasingly common subunit in recent trials is gp140. Gp140 is simply a synthetic mimic of the envelope glycoprotein spike on the surface of HIV- 1’s envelope. Thus, gp140 contains both gp120 and gp41 subunits, however, the portion of the gp41 subunits that normally anchor the spike into the virus’ envelope, gp140’s transmembrane domain, is removed to the make the complex free-floating and soluble (disulfide bonds may even be added to help support the complex). Besides the subunits themselves, gp140 subunit vaccines also include an adjuvant, typically Alum, in addition to other excipient substances to suspend the adjuvant and subunits (Kovacs et al., 2014.) Focusing back on the Ad26 vector’s mechanism of action, although Ad26 is known for only causing very minor cold-like symptoms at worst, scientists still want to ensure the Ad26

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