On February 24, the biotechnology company Moderna Therapeutics announced that it had shipped its variant-specific COVID-19 vaccine candidate, mRNA-1273.351, to the National Institutes of Health (NIH) for clinical study. In a press release, the NIH has confirmed that a Phase I clinical trial evaluating the vaccine candidate's safety and immunogenicity in adult volunteers has begun.
Viruses, variants and vaccines
In 2020, Moderna Therapeutics and the National Institute of Allergy and Infectious Diseases co-developed the mRNA-based COVID-19 vaccine mRNA-1273. After clinical studies demonstrated its safety and efficacy, the vaccine was authorized for emergency use in the United States on December 18.
What is an mRNA vaccine?
RNA-based vaccines are designed to induce antibody production in an individual against a specific pathogen and trigger immunity.
mRNA is an intermediate molecule between DNA and proteins. It is an RNA version of a gene that exits the cell's nucleus, travels to the cytoplasm and is translated to produce proteins.
An mRNA vaccine encodes antigens that are identical to or resemble a specific pathogen. When delivered into the body, the mRNA is translated and the adaptive immune system is triggered to produce antibodies against that pathogen. mRNA-1273 encodes for a perfusion-stabilized form of the SARS-CoV-2 spike protein, part of the virus's structure that enables its entry into host cells.
The SARS-CoV-2 virus has evolved, and novel variants of different geographical origin are circulating across the globe. Whilst viral mutations are anticipated, some variants can emerge that pose a risk to public health strategies such as immunization. Such variants are declared "variants of concern", or VOCS, by the Centers for Disease Control and Prevention.
In response to the emergence of the VOC B.1.351, first identified in the Republic of South Africa, Moderna has developed mRNA-1273.351, a vaccine that delivers instructions for making a SARS-CoV-2 spike (S) glycoprotein incorporating mutations found in the B.1.351 variant.
“Preliminary data show that the COVID-19 vaccines currently available in the United States should provide an adequate degree of protection against SARS-CoV-2 variants," said NIAID Director Dr Antony Fauci in a press release. "However, out of an abundance of caution, NIAID has continued its partnership with Moderna to evaluate this variant vaccine candidate should there be a need for an updated vaccine.”
Phase I trial of mRNA-1273.351
A Phase I trial of mRNA-1273.351 will recruit 210 healthy individuals aged 18 years and above across four research sites in the United States. The study includes two cohorts, with the aim being to obtain rapid information on the immunogenicity of the novel vaccine to inform short-term public health decisions.
Cohort one will include ~60 individuals aged 18 years plus that received two vaccinations of the mRNA-1273 vaccine in a previous Phase I clinical trial. These participants will receive one intramuscular injection of mRNA-1273.351 and will be observed through 12 months of follow up.
Cohort two will include ~150 participants aged 18-55 years that have not yet received a COVID-19 vaccine, and who do not have a known history of being infected with SARS-CoV-2. Subjects in this group will be assigned to one of six potential treatment arms, receiving either two or three intramuscular injections of the vaccine in addition to 12 months of follow up. The purpose of this cohort is to evaluate varying strategies for generating cross-protective immune responses in a naïve population.
The participants will be required to provide blood samples at specific timepoints in the trial that will be used to measure immune responses against circulating strains of SARS-CoV-2. According to the press release shared by the NIAID, the clinical trial will be fully enrolled by the end of April 2021. In addition to this study, a collaboration with NIAID's Vaccine Research Center and Moderna to test mRNA-1273.351 in animal models is also ongoing.