Hitting HIV with Combo Therapy

Thanks to advancements in our understanding of human immunodeficiency virus (HIV) and treatment options, HIV infection is no longer the death sentence it was in the early 1980s when AIDS, acquired immunodeficiency syndrome, was first recognized as a rapidly spreading, infectious disease. Read this article¹ for a historical overview of the emergence of HIV/AIDS. Today, several antiretroviral therapies are available that effectively suppress HIV levels in infected patients. These existing therapeutics are so successful that some medicines can also be taken as a prophylactic to prevent new infection (e.g. PrEP, pre-exposure prophylaxis).² Unfortunately, there is currently no cure and no vaccine for HIV/AIDS. Medicines must be taken periodically to keep the virus at bay.

Eradication of HIV has proven challenging because of its capacity to quickly mutate and, more problematically, to lie immunologically dormant in the very cells that normally respond to viral infection, i.e. a latent HIV reservoir forms in the T cells that would normally mount a response.¹ In the highlighted study, Usero et al. propose a combination therapy that consists of latency reversal agents (Vesatolimod, Nivolumab) and an mRNA vaccine they termed TMEP-B. TMEP-B, or T cell multiple-epitopic B, is an immunogen that contains eight different, conserved HIV epitopes.³ Read the full article to learn how the TMEP-B mRNA vaccine performed in combination with latency reversal agents in vitro.

Citation

Title: The combination of an mRNA Immunogen, a TLR7 Agonist and a PD1 Blocking Agent Enhances In-Vitro HIV T-Cell Immune Responses
Authors: Lorena Usero, Lorna Leal et al.
Journal: Vaccines, Volume 11, 28 Jan 2023.
DOI: 10.3390/vaccines11020286
Product Usage: Monocyte-derived dendritic cells (MDDCs) were generated from peripheral blood mononuclear cells isolated from patients infected with HIV. The MDDCs were resuspended in Ingenio® Electroporation Solution at 10×10⁶ million cells/ml and electroporated with 10 µg of in vitro transcribed TMEP-B mRNA or no mRNA (Mock) in a 0.4-cm gap-width cuvette. The MDDCs were assayed and used for T-cell proliferation studies 24 hours post-transfection.

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