Channels • 2022 • Volume 6 • Number 2 Page 7 carrying vectors) that would allow the patient’s body to build immunological memory against that antigen (and by extension the pathogen to which that antigen is a part). Since variations in genetic sequences, brought about by constant mutations by Reverse Transcriptase, necessarily entail variations in amino acid sequence, which, in turn, entail potential variations in viral antigens’ peptide sequences and epitopes, there are simply an overwhelming number of different HIV-1 variants that the body’s immune system’s B & TCells must be able to identify in order to combat the HIV-1 infection. Thus, scientists have been attempting to uncover ways to provide the body with antigens that would “teach” the body how to recognize the incredibly diverse strains of HIV-1. However, finding natural, or synthesizing synthetic, antigens that will stimulate the immune system to react (immunogens) and start building immunologic memory against the numerous HIV-1 strains has been incredibly difficult - especially if a more universal prophylactic HIV-1 vaccine is desired (Ng’uni et al., 2020). Furthermore, even if antigens that prime the immune system for broad coverage of HIV-1 strains are developed, the continuous mutation of HIV-1 is still a major issue. As mentioned before, as antigenic drift occurs in HIV-1, the body’s Abs and memory cells are less and less likely to recognize HIV-1 particles due to changing epitopes and peptide sequences, necessitating the immune system to conduct another primary response as “escape mutants” of HIV-1 (variants that the immune system cannot recognize) remain one step ahead of the immune system’s ability to recognize them - though some vulnerable strains can still be eliminated by the body (Su et al., 2019). One way that scientists have been looking to overcome the obstacle of needing to immunize people with antigens that provide broad immunological recognition of circulating HIV-1 strains, as well as the problem of escape mutants, is the “mosaic antigen” method. In this process, several short epitope-encoding DNA sequences (usually around 27 nucleotides long) are selected by a computer program, which chooses these sequences based on which combinations would provide epitopes with the least amount of variability among HIV-1 strains - thereby leading to broader coverage. These selected DNA sequences are then spliced together to constitute a larger DNA sequence that now encodes a sort of “frankenstein antigen” containing epitopes representing multiple HIV-1 clades. These synthetic antigens therefore not only help teach the immune system to recognize more conserved epitopes belonging to multiple HIV-1 clades that may be encountered, but hopefully also help build memory against potential, future escape mutants before those escape mutants even appear - thereby allowing the immune system to be one step ahead of the virus (Fischer et al., 2007). With this potential answer to the problem of HIV-1’s pre- existent and ever-developing genetic diversity, it’s important to now briefly discuss the aforementioned second challenge to HIV-1 vaccine development. The second challenge to developing an effective HIV-1 vaccine, is the uncertainty regarding which immune responses should be elicited in order to fight HIV-1 infection. This confusion directly impacts vaccine development, because the particular antigens that are included within a vaccine can impact the type of immune responses that are elicited. For example,
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