Study of Self-Amplifying Messenger Ribonucleic Acid (samRNA) Vaccines Against COVID-19 in Healthy Adults and People Living With Human Immunodeficiency Virus (HIV)

This Phase 1 clinical trial (CORAL-CEPI) will assess the potential of second-generation Coronavirus Disease 2019 (COVID-19) vaccines. These vaccines use a codon optimized Spike (S) cassette with additional T cell epitopes (TCE) (cassette S-TCE) covering multiple epitopes from non-spike proteins to safely drive strong, broad, and durable B cell and T cell immune responses to SARS-CoV-2. This trial will assess the potential to generate B cell and T cell responses against SARS-CoV-2 in both people living with HIV (PLWH) and HIV-negative participants, in participants who have previously been infected by SARS-CoV-2, and those who are naive to SARS-CoV-2, meaning they have neither been infected with nor vaccinated against SARS-CoV-2. GRT-R912, GRT-R914, and GRT-R918 are vaccines using a samRNA vector based and administered as either a single dose or two dose regimen, providing an option for a potent, single-modality approach.

Inclusion criteria

• Male or non-pregnant female at least 18 years and no more than 65 years of age at enrollment (Parts A, B, and C only).
• No previous SARS-CoV-2 infection or recovered.
• HIV-negative status confirmed by laboratory testing.

Additional inclusion criteria for PLWH:

• Serum positive HIV test or history of HIV infection.
• On anti-retroviral therapy for at least 3 months before screening and clinically stable.

Additional inclusion criteria for Part D (GRT-R918):

• Male or non-pregnant female between 18 and <60 years of age at enrollment.
• Male or non-pregnant female greater than or equal to 60 years of age at enrollment.
• Received any authorized SARS-CoV-2 vaccine series at least 2 months prior to study vaccine.

Exclusion criteria

• Current active infection with COVID-19.
• Positive for SARS-CoV-2 by nasal swab polymerase chain reaction (PCR) at screening.
• Currently receiving treatment or prevention agents with activity against SARS-CoV-2.
• Breastfeeding, pregnant, or planning to become pregnant during the course of the study.
• Received or plans to receive any non-study provided SARS-CoV-2 vaccine (including boost) during the study period (except for Part D).
• Received or plans to receive any live, attenuated vaccine within 28 days before or after study vaccination.
• Received or plans to receive any subunit or killed vaccine within 14 days before or after vaccination.
• Received or plans to receive immunoglobulins and/or any blood products within the 3 months preceding the planned administration of first study vaccination or at any time during the study.
• Currently active viral infection of hepatitis B virus or hepatitis C virus.

Additional exclusion criteria for PLWH:

• Screening CD4+ T cell count ≤200 cells/mcL.
• Viral load ≥10,000 virus particles/mL.
• History of opportunistic illness indicative of Stage 3 HIV infection.
• Acute febrile illness within 4 weeks before the first vaccination.

Additional exclusion criterion for Part D (GRT-R918) Cohorts D3, D4, D7, and D8:

• Received last dose of any authorized SARS-CoV-2 vaccine series within 2 months prior to study vaccine.