The National Institutes of Health has initiated the phase 1 trial of a new investigational vaccine known as mRNA-1273.351 designed to protect against the B.1.351 SARS-CoV-2 variant first identified in South Africa. The vaccine which is developed by the Massachusetts based biotechnology company Moderna will be evaluated for its safety and immunogenicity in adult volunteers.
The trial will enrol approximately 210 healthy adult volunteers at four clinical research sites in the US that are part of the Infectious Diseases Clinical Research Consortium (IDCRC).
The company’s initial anti-COVID-19 jab named mRNA-1273 vaccine, co-developed with the National Institute of Allergy and Infectious Diseases (NIAID), is currently authorised by the U.S.FDA for emergency use in the US in adults 18 years of age and older. The vaccine is administered as two 100-microgram (mcg) doses 28 days apart.
The vaccine uses lipid nanoparticles to deliver instructions to the body’s cells for making a stabilised version of the spike protein found on the surface of the SARS-CoV-2 virus. After the vaccination, the immune system detects the stabilised spike protein and begins building a response against the virus.
However, the new variant vaccine candidate, mRNA-1273.351, differs from the currently used vaccine in that it delivers instructions for making the SARS-CoV-2 spike that incorporates key mutations in the B.1.351 virus variant.
The trial will enrol people aged 18 years and older who already have received the mRNA-1273 vaccine, as well as people aged 18 to 55 years who have not received any COVID-19 vaccine.
Approximately 60 volunteers who previously received mRNA-1273 as a participant in NIAID’s phase 1 trial of mRNA-1273 (which began in March 2020) will enrol in the new variant phase 1 trial. Approximately one year ago, these volunteers received two vaccinations of mRNA-1273 28 days apart at varying doses: 50 mcg, 100 mcg or 250 mcg.
As part of the variant vaccine trial, these volunteers will be randomised to receive either a single booster vaccination of 50 mcg of mRNA-1273.351 (group 1A) or a single vaccination containing one 25-mcg dose of mRNA-1273 and one 25-mcg dose of mRNA-1273.351 (group 1B).
The remaining participants from the March 2020 trial will be offered a booster shot of mRNA-1273 as part of a separate clinical trial protocol.
The variant trial also will enrol approximately 150 volunteers aged 18 to 55 years who have not received any COVID-19 vaccine, have no known history of COVID-19 or SARS-CoV-2 infection, and do not have health conditions that are associated with an increased risk of severe illness from SARS-CoV-2 infection, such as cancer, heart conditions, type 2 diabetes mellitus, severe obesity or chronic kidney disease. These volunteers will be randomly assigned to one of the following eight cohorts:
Group 2A (15 participants)- receives three vaccinations 28 days apart: 100 mcg of mRNA-1273, followed by 100 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273.351.
Group 2B (15 participants)- receives three vaccinations 28 days apart: 50 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273.351.
Group 2C (20 participants)- receives two vaccinations 28 days apart: 100 mcg mRNA-1273.351, followed by 100 mcg of mRNA-1273.351.
Group 2D (20 participants)- receives two vaccinations 28 days apart: 50 mcg of mRNA-1273.351, followed by 50 mcg of mRNA-1273.351.
Group 2E (20 participants)- receives two vaccinations 28 days apart: 100 mcg of mRNA-1273, followed by 100 mcg of mRNA-1273.351.
Group 2F (20 participants)- receives two vaccinations 28 days apart: 50 mcg of mRNA-1273, followed by 50 mcg of mRNA-1273.351.
Group 2G (20 participants)- receives a single vaccination at their initial visit which combines 50 mcg of mRNA-1273 plus 50 mcg of mRNA-1273.351. Twenty-eight days later, they will receive another single vaccination of the same dose and combination.
Group 2H (20 participants)- receives a single vaccination at their initial visit which combines 25 mcg of mRNA-1273 plus 25 mcg of mRNA-1273.351. Twenty-eight days later, they will receive another single vaccination of the same dose and combination.
The trial will evaluate the safety and reactogenicity of the vaccine candidate as well as its ability to induce an immune response. Reactogenicity can include injection site reactions like redness and pain as well as systemic reactions such as fever, headache, fatigue or muscle aches.
Participants will be closely monitored for safety and will be asked to return to the study clinic for multiple follow-up visits between vaccinations and for additional visits during the year after their last vaccination.
Participants also will be asked to provide blood samples at specified times throughout the trial. Scientists will use these samples to measure the immune response against circulating strains of SARS-CoV-2, including the B.1.351 variant.
“The B.1.351 SARS-CoV-2 variant, first identified in the Republic of South Africa, has been detected in at least nine states in the United States. 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 Anthony S. Fauci, M.D.
The trial is led and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.