In a recent study published in medRxiv* Prepress server, researchers assessed the durability of immune responses after the third dose of BNT162b2 vaccine.
The Coronavirus 2019 (COVID-19) pandemic has negatively affected human lives and continues to represent a negative disruption to public health and the economy. Although several vaccines against the causative agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been shown to be effective against severe infections and diseases, the optimal vaccine dose schedule has not yet been determined for best results. .
The marked decline in the immune system over time after the two vaccinations has prompted many countries to recommend an additional vaccination (the third dose). A third dose quickly boosted immunity and increased the effectiveness of the vaccines. Some studies recently reported that a third dose was needed to neutralize Omicron, the newest variant of SARS-CoV-2 of concern (VOC). However, the continuity of the third vaccination is still not well defined.
In the current prospective, longitudinal cohort study, researchers assessed immunity robustness in the five months following the third vaccination.
Healthcare workers (HCWs) from Sheba Medical Center in Israel were assigned as the study cohort. Healthcare workers were asked to participate in the study if they were SARS-CoV-2-naïve before the first vaccination. Each participant underwent a serological test every four weeks. The dynamics of immunity after the third vaccination was compared with that after the second vaccination. Serological test samples were obtained from January 21, 2021 to December 21, 2021.
Diminished antibody responses in reinforced individuals during the last Omicron increase were compared between infected and uninfected participants. Immunoglobulin G (IgG) assays were performed before and after receiving the third dose, and the results were presented as binding antibody units (BAU). The strength of interactions between IgG and the SARS-CoV-2 receptor binding domain was tested.
Pseudoviral neutralization assays were performed to test the neutralization potential of sera against wild-type (WT) SARS-CoV-2 and partial neutralization assays to compare efficacy with Delta and Omicron variants using live virus. Peripheral blood mononuclear cells (PBMCs) were isolated and analyzed for SARS-CoV-2-specific T-cell activation using the ELISPOT assay. Participants were asked to get tested for COVID-19 if they had been exposed to an infected person or had known symptoms. In addition, they were required to conduct weekly tests during the Omicron surge (December 15, 2021-February 28, 2022).
Approximately 8,092 samples were collected from 3,972 healthcare workers between August 5, 2021 and December 29, 2021. Clinical follow-up data during the OMICRON SARS-CoV-2 eruption were available for 2,865 healthcare workers. IgG decline was slower after the third vaccination at 1.32% on the day compared to 2.26% on the day after the second dose. Similarly, the rate of decline of neutralizing antibodies was slower after the third dose (2.26% per day) than after the second dose (3.34% per day).
The notoriety of samples collected one and four months after the third dose was determined from 32 participants and compared with samples obtained one month after the second vaccination. Avidity averaged 97.4% in the booster samples after one month, which increased to 98.04% after four months. In contrast, it was 65.7% in the second dose samples. T-lymphocyte activity was assessed for 77 participants 7–28 days (peak response) and 85–112 days after boosting. At the peak, average T-cell activity was approximately 98 active T lymphocytes per million PBMCs and decreased to approximately 59 cells/million PBMCs within three to five months.
SARS-CoV-2 neutralization assays and variants were performed on samples collected from 25 random subjects. The mean equivalent geometric titers (GMT) were 942, 410, and 111 for the SARS-CoV-2 WT, Delta, and Omicron variants, respectively, which decreased within four months to 249 (WT), 131 (delta), and 26 (Omicron). ). Of the 2,865 healthcare workers who were followed clinically during the omicron augmentation, 1,160 participants had positive cases. The median duration from the third vaccination to the sudden cases was 147.6 days. The affected health care workers were younger than the naïve health care workers.
The authors found lower peak IgG levels after the third dose among affected participants compared to naive HCWs. Among those cases 65 years of age or older, IgG decline (1.39%/day) and nAb (1.86%/day) were faster than naive HCWs (IgG decrease: 0.99%/day, nAb: 0.52%/day) ).
The researchers observed a significantly slower decrease in humoral responses after the third BNT162b2 vaccination than the second post-dose. The diminishment of neutralizing responses against SARS-CoV-2 Omicron was similar to that of the other tested variants but significantly and persistently lower than that of the WT or Delta variants at four months. Furthermore, they observed that superinfection of the Omicron variant was associated with low-peak IgG responses.
Notably, selecting a study population who was relatively healthier and younger than the general population limits the generalizability of these findings. However, the study showed that the third dose was more sustainable than the second dose with only marginal loss of antibodies, and despite being protective, the third vaccination did not prevent penetration of SARS-CoV-2 Omicron infection.
The authors hypothesize that a new and improved vaccination strategy should be adopted to reduce the spread of COVID-19 and achieve herd immunity.
medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.
- Mayan Gilboa, Gilly Regev Yochai, Michael Mandelbaum, Victoria Endenbaum, Keren Asraf, Ronen Floss, Sharon Amit, Ella Mendelsohn, Ram Dolman, Arnon Avek, Lawrence S. Friedman, Chuck Chris, Yaniv Lustig. (2022). Durability of the immune response to a third dose of BNT162b2; Five months of follow-up. medRxiv. bang: https://doi.org/10.1101/2022.05.03.22274592 https://www.medrxiv.org/content/10.1101/2022.05.03.22274592v1