In a recent study posted to the medRxiv* preprint server, researchers evaluated the immune responses after boosting with Pfizer's BNT162b2 vaccine.
Study: Protective antibodies and T cell responses to Omicron variant three months after the booster dose of BNT162b2 vaccine. Image Credit: Shutterstock/Firn
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Background
The Omicron variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the latest variant of concern (VOC) to emerge and has caused a massive surge of coronavirus disease 2019 (COVID-19) infections in a short period. Omicron infections have been documented in vaccinated individuals, indicating that they can evade pre-existing, vaccine-induced immunity.
Moreover, the novel variant harbors more mutations than previous VOCs that confer enhanced features like immune escape and high transmissibility. Most Omicron mutations are in the spike (S) protein's receptor-binding domain (RBD), which is the target of existing vaccines.
Nonetheless, the clinical severity of disease caused by the Omicron variant is relatively lower than VOCs like the SARS-CoV-2 Delta variant. The Omicron variant evades serum neutralizing antibodies (NAbs) in doubly-vaccinated individuals and reportedly resists therapeutic antibodies.
However, a third vaccination or breakthrough infection with any SARS-CoV-2 variant other than Omicron induces a robust antibody response against the Omicron variant. Hence, three exposures to the viral antigen either through vaccination or infection can protect from severe COVID-19.
The study
The current study determined people's immune responses to a BNT162b2 booster dose by longitudinally following them for three months post-booster vaccination. Precisely, the authors ascertained the capacity of serum to incapacitate interactions between Omicron's S protein and host angiotensin-converting enzyme-2 (ACE2) with each vaccine dose, comparing it with earlier VOCs.
The study participants were diagnostics laboratory personnel immunized with three BNT162b2 doses, and the researchers previously assessed their immune responses following the second vaccination. They were fully vaccinated in January 2021 and received the vaccine booster in October 2021. Blood samples were collected from them at nine-time points – before first (B1D) and second dose (B2D), one week (1wA2D), six weeks (6wA2D), three (3mA2D), six (6mA2D), and nine months (9mA2D) after the second vaccination, two weeks (2wA3D) and three months (3mA3D) post-booster vaccination.
Findings
S-RBD IgG levels were significantly lower before the booster vaccination (9mA2D), with a median level of 739 arbitrary units per milliliter (AU/ml). It was 32899 AU/ml in samples collected at 2wA3D but dropped to 13119 AU/ml by 3mA3D. Next, the serum potential to block ACE2 and S protein interactions was tested. Serum samples were tested against the S protein of wildtype (WT) strain and Beta, Delta, and Omicron variants.
B1D samples, as expected, failed to inhibit ACE2:S interaction, but most samples from 1wA2D blocked wildtype strain, Delta, and Beta variants, but the serum inhibitory potential reduced significantly against the Omicron variant.
Booster vaccination (2wA3D) restored the inhibitory potential against all tested variants. However, 5.5% of the serum samples failed to reach the threshold when tested against the Omicron variant. More than 80% of serum samples from 3mA3D blocked the ACE2:S interactions, but the blocking activity was diminished relative to 2wA3D.
The researchers evaluated the activation-induced marker (AIM)-positive memory T lymphocytes in CD4+ and CD8+ T cell subsets pre- and post-third vaccination in addition to investigating CD4+ and CD8+ T cell responses specific to SARS-CoV-2 Omicron at 3mA3D. At 9mA2D, 84% and 58% of the participants had CD4+ and CD8+ memory T cell responses, respectively, increasing to 100% and 90% by 2wA3D. T cell stimulation was performed with a peptide pool comprising Omicron's mutated S peptides with samples from 3mA3D. The authors noted that only 17% of participants with AIM-positive T lymphocytes (against WT S protein) had CD4+ T cells non-responsive to mutated peptides. In comparison, only 15% of participants lost CD8+ responses against the mutated S epitopes.
Conclusions
The present research studied the immune dynamics of a vaccinated cohort and observed that a third BNT162b2 dose replenishes NAbs against WT SARS-CoV-2 and its VOCs. However, with two vaccine doses, the Omicron VOC had a significantly elevated ability to evade the NAbs. The Beta variant also had a similar (immune) evasive nature but lesser than Omicron VOC.
Consistent with other studies, the authors observed declining immune responses after two vaccinations and reduced blocking activity. However, booster vaccination restored the blocking potential and elevated S-RBD IgG levels. Notably, antibody levels wane after three months of booster vaccination, albeit insignificantly and much slower than that post-second vaccination.
AIM-positive CD4+ and CD8+ T cell populations remained largely stable after the second dose but increased after booster administration and retained their high proportions by 3mA3D with a slight decline of CD8+ cells relative to 2wA3D levels. Overall, these findings suggested that humoral and cellular responses increased after administering booster vaccines.
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Article Revisions
- May 12 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
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