Fourth COVID-19 Vaccine Dose Boosts Immunity Above Third Shot

A second booster, or fourth dose, of an mRNA COVID-19 vaccine increased antibody levels above the peak seen after the third shot, a new study in Britain found.

The study, published in The Lancet Infectious Diseases, included 166 participants who received fourth-dose boosters between Jan. 11 and 25, including 83 who received the Pfizer-BioNTech vaccine and 83 who received a half dose of the Moderna vaccine.

“These data show that a fourth dose of COVID-19 mRNA vaccines is well tolerated and can provide a substantial boost to both humoral and cellular immunity approximately 7 months after a third-dose booster, with anti-spike protein IgG titers at day 14 following the fourth dose higher than those at day 28 after the third dose for both BNT162b2 and mRNA-1273,” the study authors, led by Saul Faust, PhD, director of the NIHR Southampton Clinical Research Facility, wrote.

Conducted as a substudy of the COV-BOOST trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the United Kingdom, the study was funded by the National Institute for Health Research (NIHR) and the Vaccine Task Force and sponsored by University Hospital Southampton NHS Foundation Trust.

Among the participants, 88 had received the AstraZeneca vaccine as their primary course followed by a Pfizer-BioNTech booster and 78 received three doses of the Pfizer-BioNTech vaccine.

The median interval between third and fourth doses of the vaccine was 208.5 days. The median age of participants was 70.1 years, and 52% were female. Pain at the injection site and fatigue were the most common adverse events, and no serious adverse events were related to the vaccine.

Anti-spike protein IgG concentration rose to 37,460 ELISA laboratory units/mL at Day 14 after the fourth dose in the Pfizer-BioNTech group, compared with 23,325 ELU/mL at Day 28 after the third dose. In the Moderna group, the increase was even greater, rising to 54,936 ELU/mL from 25,317 ELU/mL.

The fold changes in anti-spike protein IgG titers from just before the fourth dose to Day 14 were 12.19 in the Pfizer-BioNTech group and 15.90 in the Moderna group. T-cell responses also were boosted after the fourth dose, with fold changes for the wild-type variant of 7.32 in the Pfizer-BioNTech group and 6.22 in the Moderna group.

The study authors said increased antibody titers likely would wane rapidly, and people with high antibody titers were unlikely to see as high of an increase, suggesting there might be a ceiling to the immune response.

“This study provides important data to guide policy makers who might be considering the deployment of further booster doses of COVID-19 vaccines to the clinically vulnerable or whole populations,” the authors noted.

In March, the Food and Drug Administration amended emergency use authorization for the mRNA vaccines to approve second boosters for adults age 50 and older and those age 12 and older with immunocompromise at least four months after their last booster.

In the UK, health officials have authorized fourth doses of the vaccines for those age 75 and older along and other vulnerable populations.

“These results underline the benefits of the most vulnerable people receiving current spring boosters and gives confidence for any prospective autumn booster programme in the UK, if the Joint Committee on Vaccination and Immunisation considers it needed at that time,” Faust said in a news release.

The study provides further evidence of the importance of getting booster shots as soon as eligible, the UK’s Health and Social Care Secretary Sajid Javid said in the news release.

“We’re able to live with COVID thanks to the protection provided by our phenomenal vaccine programme and a booster dose will top up your immunity to continue to keep you and your loved ones safe,” he said.