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Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

ABSTRACT: Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort of health care workers followed serologically since April 2020. All 45 individuals had received two doses of the Pfizer-BioNTech BNT162b2 vaccine with a delayed booster at 10 weeks. Absolute and neutralizing antibody titers against wild-type SARS-CoV-2 and variants were measured using enzyme immunoassays and pseudotype neutralization assays. We observed antibody reactivity against lineage A, B.1.351, and P.1 variants with increasing antigenic exposure, through either vaccination or natural infection. This improvement was further confirmed in neutralization assays using fixed dilutions of serum samples. The impact of antigenic exposure was more evident in enzyme immunoassays measuring SARS-CoV-2 spike protein–specific IgG antibody concentrations. Our data show that multiple exposures to SARS-CoV-2 spike protein in the context of a delayed booster expand the neutralizing breadth of the antibody response to neutralization-resistant SARS-CoV-2 variants. This suggests that additional vaccine boosts may be beneficial in improving immune responses against future SARS-CoV-2 variants of concern.

SUBMITTER: Urbanowicz RA

PROVIDER: S-EPMC9835846 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

Urbanowicz Richard A RA Tsoleridis Theocharis T Jackson Hannah J HJ Cusin Lola L Duncan Joshua D JD Chappell Joseph G JG Tarr Alexander W AW Nightingale Jessica J Norrish Alan R AR Ikram Adeel A Marson Ben B Craxford Simon J SJ Kelly Anthony A Aithal Guruprasad P GP Vijay Amrita A Tighe Patrick J PJ Ball Jonathan K JK Valdes Ana M AM Ollivere Benjamin J BJ

Science translational medicine 20210805 609

Understanding the impact of prior infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the response to vaccination is a priority for responding to the coronavirus disease 2019 (COVID-19) pandemic. In particular, it is necessary to understand how prior infection plus vaccination can modulate immune responses against variants of concern. To address this, we sampled 20 individuals with and 25 individuals without confirmed previous SARS-CoV-2 infection from a large cohort o ...[more]

PMID: 34376569

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Project description:ImportanceAlthough 2 and 3 doses of vaccine have been implemented against the SARS-CoV-2 pandemic, the level of immunity achieved by these additional vaccinations remains unclear.ObjectiveTo investigate the induction of neutralizing antibodies against the SARS-CoV-2 Omicron variant after 2 and 3 doses of the BNT162b2 messenger RNA (mRNA) vaccine among recipients of different ages.Design, setting, and participantsA cohort study was conducted from June 1, 2021, to January 12, 2022, among 82 physicians at Kobe University Hospital who had received 2 doses of the BNT162b2 mRNA vaccine.Main outcomes and measuresThe rates of positive test results and the titers of neutralizing antibodies against the Omicron variant after 2 and 3 doses of the vaccine were compared with those against other variants and compared among 3 age groups (≤38 years [younger age group], 39-58 years [intermediate age group], and ≥59 years [older age group]).ResultsA total of 82 physicians (71 men [87%]; median age, 44 years [IQR, 33-58 years]) participated; 31 (38%) were in the younger age group, 32 (39%) were in the intermediate age group, and 19 (23%) were in the older age group. At 2 months after 2 doses of the vaccine, 23 participants (28%) had neutralizing antibodies against the Omicron variant, with a titer of 1.3 (95% CI, 1.2-1.4), which was 11.8-fold (95% CI, 9.9-13.9) lower than the titer against the D614G variant and the lowest among the variants tested. Although the titer of the neutralizing antibody against the Delta variant tended to be low among the older age group (2.9 [95% CI, 2.0-4.1]), the titers of the neutralizing antibody against the Omicron variant were low among all age groups (younger age group, 1.3 [95% CI, 1.1-1.6]; intermediate age group, 1.3 (95% CI, [95% CI, 1.1-1.5]; and older age group, 1.2 [95% CI, 1.0-1.4]). At 7 months after 2 doses of the vaccine, 5 participants (6%) had the neutralizing antibody against the Omicron variant, but after the booster (third dose) vaccination, all 72 participants who received the booster had the neutralizing antibody, and the titer was 41 (95% CI, 34-49), much higher than that at 7 months after 2 doses of the vaccine (1.0 [95% CI, 1.0-1.1]). This increase in titers was observed regardless of age groups; the titers were 44 (95% CI, 32-59) among the younger age group, 44 (95% CI, 32-59) among the intermediate age group, and 30 (95% CI, 22-41) among the older age group.Conclusions and relevanceIn this cohort study of 82 Japanese participants, 2 doses of the BNT162b2 mRNA vaccine did not induce sufficient neutralizing antibody against the Omicron variant. However, booster vaccination was associated with induction of a high level of neutralizing antibodies against the Omicron variant, irrespective of the recipient's age.

Project description:ImportanceThe factors associated with long-term serum levels of anti-SARS-CoV-2 antibodies after COVID-19 vaccination in healthy individuals have rarely been investigated.ObjectiveTo investigate factors associated with anti-SARS-CoV-2 antibody levels.Design, setting, and participantsThis prospective cohort study included health care workers at Kyungpook National University Chilgok Hospital (Daegu, Korea) with no history of SARS-CoV-2 infection who received 2 doses of the BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech; first dose, March 17-20, 2021; second dose, April 7-10, 2021). Serum samples were collected at 2, 4, and 6 months after the second injection.InterventionsSARS-CoV-2 BNT162b2 mRNA vaccine.Main outcomes and measuresAnti-SARS-CoV-2 specific antibodies were measured using enzyme-linked immunosorbent assay kits up to 6 months after the receipt of 2 doses of the BNT162b2 mRNA COVID-19 vaccine. The main outcome was factors associated with anti-SARS-CoV-2 antibody levels at 6 months.ResultsAll 50 participants (mean [SD] age, 34.7 [9.4] years; 10 [20.0%] male; mean [SD] body mass index, 21.8 [5.4]) acquired anti-SARS-CoV-2 antibodies and maintained positive antibody (cutoff ≥30%) up to 6 months. The mean serum antibody level decreased with time (91.9%, 89.3%, and 81.5% at 2, 4, and 6 months, respectively). Serum antibody levels at 6 months were correlated with antibody levels at 2 months (R = 0.944; P < .001). The anti-SARS-CoV-2-specific antibody level was inversely correlated with weight, body mass index, body fat amount, and body weight to height ratio in Spearman correlation analysis. A 1-SD increase in body weight, weight to height ratio, and body mass index was associated with a 4%- to 5%-decrease in anti-SARS-CoV-2 antibodies in multiple linear regression analysis for women. In multivariate analysis for categorized variables, lower serum level of antibody (ie, <81.5%) was associated with weight (weight ≥55 kg: odds ratio, 9.01; 95% CI, 1.44-56.40). The probabilities of less than 70% and less than 80% antibody at 6 months were 0% and 11% in participants weighing less than 55 kg, respectively, but 16% and 42% in participants weighing 55 kg or greater.Conclusions and relevanceIn this study, the inverse correlation of anti-SARS-CoV-2-specific antibody levels with weight was sustained up to 6 months after vaccination. A booster shot of BNT162b2 mRNA vaccination may be given later than 6 months after the second dose in young and middle-aged healthy persons with low body weight.

Project description:ObjectivesCOVID-19 patients affected by haematological malignancies have a more severe course of the disease and higher mortality, prompting for effective prophylaxis. The present study aims to evaluate the humoral response after mRNA vaccination as well as the impact of a third vaccine dose in patients with lymphoid malignancies.MethodsWe conducted a single-centre study, evaluating the serological responses of mRNA vaccination amongst a cohort of 200 patients affected by lymphoid malignancies after two or three doses using an industrial SARS-CoV-2 serology assay for anti-receptor binding domain (RBD) Spike IgG detection and quantification.ResultsAmong patients with plasma cell disorders, 59 of 96 (61%) had seroconversion (anti-RBD >50 AU/mL), and recent anti-CD38 therapies were associated with lower serological anti-RBD IgG concentrations (median IgG concentration 137 (IQR 0-512) AU/mL vs. 543 (IQR 35-3496) AU/mL; p < 0.001). Patients with B-cell malignancies had a lower seroconversion rate (20/84, 24%) mainly due to the broad usage of anti-CD20 monoclonal antibodies; only 2 of 53 (4%) patients treated by anti-CD20 antibodies during the last 12 months experienced a seroconversion. A total of 78 patients (44 with plasma cell disorders, 27 with B-cell malignancies, and 7 with other lymphomas) received a third dose of vaccine. The seroconversion rate and antibody concentrations increased significantly, especially in patients with plasma cell disorders, where an increment of anti-RBD IgG concentrations was observed in 31 of 44 (70%) patients, with an anti-RBD concentration median-fold increase of 10.6 (IQR 2.4-25.5). Its benefit in B-cell malignancies is uncertain, with only 2 of 25 (8%) patients having seroconverted after the vaccine booster, without increased median antibody concentration.DiscussionA third mRNA vaccine dose significantly improved humoral responses among patients with plasma cell disorders, whereas the effect was limited among patients with B-cell malignancies.

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Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

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Two doses of the SARS-CoV-2 BNT162b2 vaccine enhance antibody responses to variants in individuals with prior SARS-CoV-2 infection.

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