Researchers at the National Institutes of Health (NIH) have started a Phase 1/2 clinical trial to examine the safety and immunogenicity of mixed boosted regimens. Adults, who have been fully vaccinated with any of the one of the three FDA-approved Covid-19 vaccines for emergency use in the United States, the Johnson & Johnson, Moderna or Pfizer vaccines, will be included in the trial.
The 150 study participants will be administered booster doses of different Covid-19 vaccines.
Each vaccine group will enrol about 25 people aged 18-55 years and around 25 people aged ≥56 years. The participants will receive a single booster dose of the Moderna COVID-19 vaccine as part of the trial 12-20 weeks following their initial vaccination regimen.
People who have not yet taken Covid-19 vaccine can also take part in the trial as a separate cohort. They will be given two doses of Moderna vaccine and will be assigned to receive a booster dose of a vaccine about 12 to 20 weeks later.
The follow up period after the last vaccination will be one year and will include telephone check-ins as well as in-person follow up visits. Participants will be examined for safety and any side effects post-vaccination. Periodic blood tests would be done to evaluate immune responses against current circulating strains of SARS-CoV-2, as well as emerging variants. Genome sequencing study would be done if the trial participants develop laboratory-confirmed symptomatic COVID-19 to see if a variant strain of SARS-CoV-2 caused the infection.
The trial has an adaptive design and may add more arms in the trial as new vaccines will be given EUA and/or variant lineage vaccines become available for evaluation. The initial results are expected in late summer this year.
Trials on mixing of vaccines have been conducted in the UK and Spain.
The phase II CombivacS trial from Spain evaluated people who had already received one dose of AstraZeneca vaccine and were then given a dose of the Pfizer vaccine. A 30 to 40 times higher antibody (IgG) response was noted after the follow up Pfizer dose vis-à-vis the control group who had only received one dose of the AstraZeneca vaccine. Most observed side effects were mild or moderate and short lived i.e. restricted to the first 2-3 days after receiving the vaccine.
Preliminary safety results from the Com-Cov vaccine trial from UK, which examined mixing of the AstraZeneca (initial dose) and the Pfizer vaccine (Follow up dose) showed an increase in the frequency of mild-moderate symptoms in those receiving either mixed dosing schedule. Adverse reactions were short-lived, with no other safety concerns. Data on immunogenicity is not yet available.
India is also likely to conduct a study to test the safety and immunogenicity of mixing of two vaccine doses.
The SARS-CoV-2 virus is mutating and many variants of concern have emerged during this pandemic. Trials have investigated the effectiveness of the current vaccines against the variants. The Delta variant, B.1.617.2, first detected in India, is now rapidly spreading globally.
Dr Anthony S. Fauci, M.D. Director National Institute of Allergy and Infectious Diseases (NIAID has very succinctly said, “Although the vaccines currently authorized by the U.S. Food and Drug Administration offer strong protection against COVID-19, we need to prepare for the possibility of needing booster shots to counter waning immunity and to keep pace with an evolving virus. The results of this trial are intended to inform public health policy decisions on the potential use of mixed vaccine schedules should booster doses be indicated.”
Mixing of Covid-19 vaccines is not recommended yet and lot more data will be required supporting the efficacy, safety and immunogenicity of this approach. If successful, mixing of vaccines or heterologous vaccination will be a welcome strategy to tide over challenges such as vaccine shortage or supply shocks that may hamper the pace of the vaccination.
(Source: NIH Press Release, June 1, 2021)
Dr Sanjay Kalra, DM, Bharti Hospital, Karnal
Immediate Past President, Endocrine Society of India