WITHDRAWN

Abstract:

Although the world’s attention is rightfully focused on the ongoing COVID-19 pandemic, the human immunodeficiency virus (HIV) pandemic is decades old and has affected many persons worldwide.  In 2020, roughly 37.7 million persons globally were living with HIV, with 1.5 million newly infected, and 680,000 persons who died of opportunistic illnesses due to acquired immunodeficiency syndrome (AIDS).  Since the beginning of the HIV pandemic in 1981, there have been 79.3 million persons infected with HIV, and 36.3 million have died of AIDS-related illnesses.  Although a cure or vaccine does not exist for HIV/AIDS, antiretroviral therapy (ART) can delay the onset of AIDS effectively managing HIV infection.  A successful ART cocktail typically includes a mixture of drugs that inhibit the viral lifecycle at several key steps: adhesion, synthesis, and/or virion release.  Common ART targets include viral integrase, protease, or reverse transcriptase.  Additionally, gp120 is the HIV viral glycoprotein found on the surfaces of infectious HIV virions used to adhere to target human CD4 and CCR5 proteins enriched on the surfaces of helper T cells (CD4⁺ T_H cells).  HIV-infected T_H cells typically execute apoptosis upon viral detection by pathogen recognition receptors (PRRs).  Typically, hematopoietic stem cells (HSCs) replace apoptosed T lymphocytes, but eventually hematopoiesis is insufficient to replace helper T cell lineages in untreated HIV-infected individuals.  As helper T cells are critically important in the full activation of the adaptive immune response, loss of a naïve helper T cellular population results in failure to generate T_H1 and T_H2 effector lineages, resulting in failure to activate the cell-mediated and humoral responses, respectively.  Here we show our RNA vaccine design against the HIV gp120, leveraging conservation at the amino acid level across manually curated reference HIV genomic sequences.  Our RNA vaccine immunogen is additionally checked for potential anaphylaxis in humans, and we hope that one day it might be clinically tested via lipid nanoparticle means of delivery.  If our vaccine works, it should in theory generate neutralizing antibodies directed against the gp120 surface epitopes, occluding virion adhesion to host helper T lymphocyte populations.  Such a vaccine might complement existing ART treatments and help relieve the global burden of HIV