A Single Dose SARS-CoV-2 Replicon RNA Vaccine Induces Cellular and Humoral Immune Responses in Simian Immunodeficiency Virus Infected and Uninfected Pigtail Macaques

Abstract

The ongoing COVID-19 vaccine rollout is critical for reducing SARS-CoV-2 infections, hospitalizations, and deaths worldwide. Unfortunately, massive disparities exist in getting vaccines to vulnerable populations, including people living with HIV. Preliminary studies indicate that COVID-19 mRNA vaccines are safe and immunogenic in people living with HIV that are virally suppressed with potent antiretroviral therapy but may be less efficacious in immunocompromised individuals. This raises the concern that COVID-19 vaccines may be less effective in resource poor settings with limited access to antiretroviral therapy. Here, we evaluated the immunogenicity of a single dose COVID-19 replicon RNA vaccine expressing Spike protein (A.1) from SARS-CoV-2 (repRNA-CoV2S) in immunocompromised, SIV infected and immune competent, naïve pigtail macaques. Moderate vaccine-specific cellular Th1 T-cell responses and binding and neutralizing antibodies were induced by repRNA-CoV2S in SIV infected animals and naïve animals. Furthermore, vaccine immunogenicity was elicited even among the animals with the highest SIV viral burden or lowest peripheral CD4 counts prior to immunization. This study provides evidence that a SARS-CoV-2 repRNA vaccine could be employed to induce strong immunity against COVID-19 in HIV infected and other immunocompromised individuals.

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…First reports showed that most PLWH responded to mRNA vaccination in terms of binding and neutralizing Ab (82). This was consistent with observations made in a simian animal model (83). However, two recent reports stressed that patients with advanced HIV infection had lower response to mRNA vaccination (15,84).…”

Self-Amplifying RNA: A Second Revolution of mRNA Vaccines against COVID-19

“…In addition, this vaccine was evaluated in a proof-of-concept study using simian immunodeficiency virus (SIV)-infected pigtail macaques. A single dose of the vaccine was able to trigger humoral responses against the S protein in some animals, with a slightly better induction of nAbs in those receiving the highest dose (25 µg) compared to the lowest dose (5 µg) [ 49 ]. Although cellular responses were modest, this pilot study suggests that saRNA vaccines could be employed successfully in HIV-infected and other immunocompromised individuals, a particularly vulnerable population where the efficacy of approved SARS-CoV-2 mRNA vaccines has been reported to be lower [ 50 , 51 , 52 ].…”