Despite being developed to fight the original COVID-19 strain, a third dose of mRNA vaccine boosts the immune system substantially to better fight infections caused by the Omicron variant relative to the standard 2-dose primary series, according to two new studies in Nature and JAMA Network Open.
Broader B-cell memory response
One mechanism by which the booster dose fights Omicron is by increasing the range of memory B cells in the recipient, the Nature researchers write. The B cells then help produce broadly neutralizing antibodies, more than 50% of which were capable of neutralizing Omicron in a study of 42 adult volunteers.
To conduct the study, researchers assessed the longitudinal immune responses of volunteers who received the primary two-dose vaccine series plus a booster shot. None of the volunteers—all healthy adults—had previously been infected with any strain of SARS-CoV-2. The study took place in 2021, with 34 volunteers receiving the Pfizer-BioNTech vaccine and 8 receiving the Moderna vaccine.
Blood samples were taken 2.5 weeks after the prime dose, 1.3 and 5 months after the second dose, and 1 month after the third dose. Following a 7.3-fold decrease in neutralizing titers between 1.3 and 5 months after the second vaccine dose, administration of a booster dose raised neutralizing titers 11.9-fold, the authors found.
To determine how neutralizing antibodies after the booster dose held up against different strains of the virus, the researchers compared 18 antibody pairs that were randomly selected across participants and had measurable neutralizing activity against the original virus strain. They then challenged the samples with both Delta and Omicron BA.1 strains of SARS-CoV-2. Fifteen of 18 antibody pairs neutralized Delta, and 11 out of 18 pairs showed neutralizing activity against Omicron.
"The memory B cells expressing more potent and broader antibodies do not appear to contribute to circulating plasma antibody levels, but upon challenge with antigen in the form of a vaccine or infection, they produce large amounts of antibodies within 3-5 days," the authors concluded. "A diversified and expanded memory B cell compartment are likely to be key mechanisms that contribute to the enhanced protection against severe disease by a 3rd mRNA vaccine dose."
Despite mutations, T cells recognized Omicron
In the JAMA Network Open study, researchers demonstrated good T-cell immune response of vaccines from Omicron in 61 Italian volunteers who had different vaccination and infection histories.
The volunteers donated 15 milliliters of blood to researchers, who then processed the samples to measure T-cell reactivity to the mutated regions of the spike protein of the Omicron variant.
The median (range) frequency of CD4+ T cells reactive to peptides covering the mutated regions in the Omicron variant was 0.039% (0%-2.356%), a decrease of 64% compared with the frequency of CD4+ cells specific for the same regions of the ancestral strain (0.109% [0%-2.376%]), the authors found.
The reduction was 49% for CD8+ T cells. But the overall reactivity to the peptide library of the full-length protein was largely maintained (estimated 87%), which means the SARS-CoV-2 Omicron variant was recognized by the cellular component of the immune system.
The Omicron variant has more than 35 mutations in the spike protein compared to the original, Wuhan strain, the authors note.
"However, as these regions cover only a small proportion of the whole protein, the overall response against Omicron spike was largely preserved regardless of vaccination and/or infection history in our study," they said.
The results mean that both vaccination and previous infection with COVID-19 likely prevent severe illness and death from the Omicron strain.