Sheeva Shahinfar

Introduction.  COVID-19 vaccine production shed light on the novelty of using mRNA vaccines to prevent chronic illness. In 2021, Moderna announced their quest to manufacture an mRNA vaccine against HIV, a chronic illness affecting approximately 38 million people worldwide.⁴ In order to develop a suitable HIV vaccine, two properties are essential: antibody dependent cellular cytotoxicity (ADCC) and long-lived antibody response. Multiple somatic hypermutations and long complementarity determining regions pose two challenges in achieving this goal. Key vaccine trials and a reflection on lessons that may be gleaned for future vaccine development are discussed. Methods. One foundational study described an mRNA-LNP vaccine encoding clade C HIV-1 Env 1086C and tested tier 1, 2, and 3 neutralization capability.⁶ A second study compared the efficacy of HIV-1 Env mRNA versus recombinant protein. They further compared a gp160 mRNA vaccine with a SOSIP gp140 mRNA vaccine and SOSIP gp140 protein vaccine.⁹ SOSIPs are near-native trimers that resemble infectious HIV virions. A third experiment compared an mRNA vaccine encoding HIV-1 Gag, Pol, and Nef proteins to another mRNA vaccine with an additional 1-methyl-3’-pseudouridylyl modified vector. Subjects were boosted with a poxvirus booster carrying the same antigen.⁴ A fourth experiment compared the efficacy of a trivalent versus tetravalent adjuvanted protein vaccine.³ The final experiment, done by Moderna, analyzed the efficacy of an mRNA vaccine that co-expressed HIV-1 426c.3dg Env and SIVmac239 Gag proteins.¹⁰ Results. The first study failed to produce recall antibody response and recommended future trials use next-generation SOSIPs. ⁸ The second study incorporated SOSIPs, but did not produce significant recall antibody responses compared to other vaccines.⁶ The third study showed promising results with vaccination with a poxvirus booster.⁹ The fourth study showed a higher antibody response and enhanced recall in tetravalent vaccines and is currently undergoing further testing.³ The final trial vaccinated subjects 10 times – results showed a 79% reduction in per-exposure risk for vaccinated subjects as compared to controls.¹⁰ Conclusion. mRNA vaccines have a marked advantage compared to other vaccines – there are less manufacturing challenges, quicker production time, and decreased cost. Incorporating several boosters, particularly utilizing different mechanisms and vehicles, shows promising results. The COVID-19 vaccine rollout provides a layout for arranging international rollout. It may be likely that at-risk patients be treated with multiple treatments for HIV including a combination of several vaccines and drugs. Nevertheless, communities must be engaged early on and support the diversity and flexibility necessary in HIV vaccine development.

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