Dynamics of SARS-CoV-2 Antibody Response to CoronaVac followed by Booster Dose of BNT162b2 Vaccine

We evaluated the longitudinal dynamics of antibody response to the SARS-CoV-2 vaccine CoronaVac and the effect of a booster dose of BNT162b2 vaccine. We found a robust antibody response after the second dose of CoronaVac that wanes over time. The response was recovered by BNT162b2, which boosted anti-spike antibody titers.     

Kinetics of SARS-CoV-2 anti-S IgG after BNT162b2 vaccination

Deployment of the BNT162b2 mRNA Covid-19 Vaccine in Israel began in December 2020.This is a retrospective analysis of serological data, showing SARS-CoV-2 anti-S IgG kinetics in 116 Israeli health care workers receiving BNT162b2.Sero-conversion occurred in 14 days in all study participants, with IgG levels peaking approximately 30 days after initiation of the vaccination series.A statistically significant difference was observed in IgG levels between subjects younger than 50 years and older participants, although in all cases, IgG levels were well above the level considered reactive by the test's manufacturer.The importance of this difference needs to be studied further, but a potential difference in vaccine efficacy and vaccine effect length could possibly be present between these two groups.     

Association between reactogenicity and SARS-CoV-2 antibodies after the second dose of the BNT162b2 COVID-19 vaccine

High vaccine reactogenicities may reflect stronger immune responses, but the epidemiological evidence for coronavirus disease 2019 (COVID-19) vaccines is sparse and inconsistent. We observed that a fever of ≥38℃ after two doses of the BNT162b2 vaccine was associated with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike IgG titers.     

Self-Reported and Physiologic Reactions to Third BNT162b2 mRNA COVID-19 (Booster) Vaccine Dose

Despite extensive technological advances in recent years, objective and continuous assessment of physiologic measures after vaccination is rarely performed. We conducted a prospective observational study to evaluate short-term self-reported and physiologic reactions to the booster BNT162b2 mRNA (Pfizer-BioNTech, https://www.pfizer.com) vaccine dose. A total of 1,609 participants were equipped with smartwatches and completed daily questionnaires through a dedicated mobile application. The extent of systemic reactions reported after the booster dose was similar to that of the second dose and considerably greater than that of the first dose. Analyses of objective heart rate and heart rate variability measures recorded by smartwatches further supported this finding. Subjective and objective reactions after the booster dose were more apparent in younger participants and in participants who did not have underlying medical conditions. Our findings further support the safety of the booster dose from subjective and objective perspectives and underscore the need for integrating wearables in clinical trials.     

Humoral and cellular immune response dynamics in Japanese healthcare workers up to six months after receiving a third dose of BNT162b2 monovalent vaccine

Longitudinal data on the immune response from the first dose to several months after the third dose of COVID-19 vaccine are limited. We analyzed the immune response in 406 Japanese healthcare workers who received at least three doses of vaccine. The geometric mean anti-receptor binding domain IgG antibody titers and antigen-stimulated T-cell interferon-gamma levels after 6 months after receiving a third dose were similar to those 8 weeks after receiving a second dose. Humoral and cellular immunity induced by the third dose was more durable than that induced by the second dose.UMIN Clinical Trials Registry ID: UMIN000043340.     

Effectiveness of BNT162b2 Vaccine Booster against SARS-CoV-2 Infection and Breakthrough Complications,Israel

We estimated vaccine effectiveness (VE) of the BNT162b2 (Pfizer-BioNTech, https://www.pfizer.com) booster dose against SARS-CoV-2 infection and reduction of complications (hospitalization, severe disease, and death) among breakthrough cases in persons in Israel >16 years of age for <20 weeks. VE estimates reached 96.8% (95% CI 96.0%–97.5%) for persons 16–59 years of age and 93.1% (95% CI 91.8%–94.2%) for persons >60 years of age on week 3. VE estimates remained at these levels for 8 weeks in the 16–59 age group and 11 weeks in those >60. A slow decline followed, becoming more pronounced in the last 2–3 weeks of evaluation. Estimates in the last week of evaluation were 77.6% (95% CI 68.4%–84.2%) and 61.3% (52.5%–68.4%) for persons 16–59 years and >60 years, respectively. The more pronounced VE decline coincided with rapid increase in Omicron variant activity. Rate reduction of breakthrough complications remained moderate to high throughout the evaluation.     

Immunological features that associate with the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2

Predictive clinical factors associated with favorable responses to BNT162b2 mRNA vaccine against SARS-CoV-2 have been reported in some studies; however, there is a subgroup with low antibody titers without well-known clinical factors reducing antibody responses. To clarify the immunological backgrounds that underlie the difference in antibody responses, we analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1774 healthcare workers who received BNT162b2 mRNA vaccine. A higher percentage of B cells before vaccination was associated with a higher antibody titer. Among B cells, naïve and transitional B cell frequencies were positively correlated with a higher antibody titer, whereas the frequencies of late memory B cells and plasmablasts were associated with a lower antibody titer. Fold change in the frequency of activated CD8⁺ T cells upon vaccination was also correlated with high antibody titers.     

Antibody levels after BNT162b2 vaccine booster and SARS-CoV-2 Omicron infection

In the present study, immunogenicity data in 61 vaccinated healthcare workers (HCWs) either infection naïve (naïve HCWs) or with infection of Delta and/or Omicron COVID-19 (experienced HCWs) were evaluated up to 270 days after the second dose of BNT162b2 vaccine and up to 90 days after a booster dose. A decrease in antibody levels at 270 days following administration of the second dose (p = 0.0335) was observed, although values did not fall below the positivity threshold (33.8 BAU/ml). After booster vaccination, antibody levels increased after 30 days (p = 0.0486), with much higher values than after first and second vaccination. Antibody levels then decreased at 60 and 90 days after the booster dose. A comparison between mean antibody levels of naïve and experienced HCWs revealed higher values in experienced HCWs, resulting from both natural and vaccination-induced immunity. A total of 14.7% of HCWs contracted the Omicron virus variant after the vaccine booster, although none showed severe symptoms. These results support that a booster dose results in a marked increase in antibody response that subsequently decreases over time.     

Association of total and neutralizing SARS-CoV-2 spike -receptor binding domain antibodies with epidemiological and clinical characteristics after immunization with the 1st and 2nd doses of the BNT162b2 vaccine

BackgroundData regarding the association of antibody levels elicited after immunization with the BNT162b2 mRNA COVID-19 vaccine with epidemiological and clinical parameters are limited.MethodsWe prospectively measured the total (TAbs-RBD) and the neutralizing antibodies (NAbs-RBD) against the receptor binding domain (RBD) of SARS-CoV-2 spike protein in a cohort of 268 Healthcare workers before immunization, 20 days after the 1^st dose and 30 days after the 2^nd dose of the BNT162b2 vaccine. A statistical analysis for possible association of antibodies’ levels with epidemiological and clinical parameters was performed.ResultsThe mean age (±SD) of the participants was 45.45 years (±11.93) (range: 24–70 years) and 211 (79.9%) were females. Statistically significant differences were detected regarding both TAbs-RBD and NAbs-RBD between the first and second doses of the vaccine (P < 0.001). The median (IQR) percentage (%) of NAbs-RBD after the 1^st dose was 51.07% (31.60%) and after the 2^nd dose 95.31% (3.70%) (P < 0.001). The correlation between the TAbs-RBD and NAbs-RBD was after the 1^st dose, Spearman’s, rho: 0.861 (P < 0.001) and after the 2^nd dose rho: 0.989 (P < 0.001). Twenty days after the 1^st dose, 56/264 (21.2%) of the participants had low levels of NAbs-RBD, while one month after the 2^nd dose all of them had protective levels of NAbs-RBD. After the 2^nd vaccine dose, a statistically significant negative association of TAbs-RBD was detected for age (P < 0.001), smoking (P = 0.011), and immunosuppressive medications (P < 0.001), while a positive association was detected for BMI (P = 0.004) and systemic adverse events after immunization (P = 0.001).ConclusionA significant correlation of TAbs-RBD and NAbs-RBD was detected after both vaccine doses. Older age, smoking, and immunosuppressive medications negatively affected the final antibody level after SARS-CoV-2 immunization. Our findings emphasize the significance of the 2^nd vaccine dose especially in the older age groups.     

Second dose of the BNT162b2 mRNA vaccine: Value of timely administration but questionable necessity among the seropositive

This study monitored titers of neutralizing IgG against the receptor-binding domain of the SARS-CoV-2 S1 subunit 14 days post-injection of each dose of the BNT162b2 mRNA Covid-19 vaccine in 401 Greek healthcare workers aged 20–67. After the first dose, titers varied upon age and history of infection, being lower in the 50+ age group and significantly higher among the seropositive. After the second dose, immunogenicity was significantly boosted in the age 50+ and SARS-CoV-2-naïve individuals, indicating the effectuality of its timely administration, yet questioning its value among the seropositive.     

T-Cell Mediated Response after Primary and Booster SARS-CoV-2 Messenger RNA Vaccination in Nursing Home Residents

ObjectivesNursing home (NH) residents have been significantly affected by the coronavirus disease 2019 (COVID-19) pandemic. Studies addressing the immune responses induced by COVID-19 vaccines in NH residents have documented a good postvaccination antibody response and the beneficial effect of a third booster vaccine dose. Less is known about vaccine-induced activation of cell-mediated immune response in frail older individuals in the long term. The aim of the present study is to monitor messenger RNA SARS-CoV-2 vaccine-induced T-cell responses in a sample of Italian NH residents who received primary vaccine series and a third booster dose and to assess the interaction between T-cell responses and humoral immunity.DesignLongitudinal cohort study.Setting and ParticipantsThirty-four residents vaccinated with BNT162b2 messenger RNA SARS-CoV-2 vaccine between February and April 2021 and who received a third BNT162b2 booster dose between October and November 2021 were assessed for vaccine-induced immunity 6 (prebooster) and 12 (postbooster) months after the first BNT162b2 vaccine dose.MethodsPre- and postbooster cell-mediated immunity was assessed by intracellular cytokine staining of peripheral blood mononuclear cells stimulated in vitro with peptides covering the immunodominant sequence of SARS-CoV-2 spike protein. The simultaneous production of interferon-γ, tumor necrosis factor-α, and interleukin-2 was measured. Humoral immunity was assessed in parallel by measuring serum concentration of antitrimeric spike IgG antibodies.ResultsBefore the booster vaccination, 31 out of 34 NH residents had a positive cell-mediated immunity response to spike. Postbooster, 28 out of 34 had a positive response. Residents without a previous history of SARS-CoV-2 infection, who had a lower response prior the booster administration, showed a greater increase of T-cell responses after the vaccine booster dose. Humoral and cell-mediated immunity were, in part, correlated but only before booster vaccine administration.Conclusions and ImplicationsThe administration of the booster vaccine dose restored spike-specific T-cell responses in SARS-CoV-2 naïve residents who responded poorly to the first immunization, while a previous SARS-CoV-2 infection had an impact on the magnitude of vaccine-induced cell-mediated immunity at earlier time points. Our findings imply the need for a continuous monitoring of the immune status of frail NH residents to adapt future SARS-CoV-2 vaccination strategies.     

BNT162b2 mRNA COVID-19 against symptomatic Omicron infection following a mass vaccination campaign in southern Brazil: A prospective test-negative design study

BackgroundEvidence regarding effectiveness of BNT162b2 mRNA COVID-19 vaccine against Omicron in Latin America is limited. We estimated BNT162b2 effectiveness against symptomatic COVID-19 in Brazil when Omicron was predominant.MethodsThis prospective test-negative, case-control study was conducted in Toledo, Brazil, following a mass COVID-19 vaccination with BNT162b2. Patients were included if they were aged ≥12 years, sought care for acute respiratory symptoms in the public health system between November 3, 2021 and June 20, 2022, and were tested for SARS-CoV-2 using RT-PCR. In the primary analysis, we determined the effectiveness of two doses of BNT162b2 against symptomatic COVID-19.ResultsA total of 4,574 were enrolled; of these, 1,758 patients (586 cases and 1,172 controls) were included in the primary analysis. Mean age was 27.7 years, 53.8 % were women, and 90.1 % had a Charlson comorbidity index of zero. Omicron accounted for >97 % of all identified SARS-CoV-2 variants, with BA.1 and BA.2 accounting for 84.3 % and 12.6 %, respectively. Overall adjusted estimate of two-dose vaccine effectiveness against symptomatic COVID-19 was 46.7 % (95 %CI, 19.9 %–64.6 %) after a median time between the second dose and the beginning of COVID-19 symptoms of 94 days (IQR, 60–139 days). Effectiveness waned from 77.7 % at 7–29 days after receipt of a second dose to <30 % (non-significant) after ≥120 days.ConclusionIn a relatively young and healthy Brazilian population, two doses of BNT162b2 provided protection against symptomatic Omicron infection. However, this protection waned significantly over time, underscoring the need for boosting with variant-adapted vaccines in this population prior to waves of disease activity.Trial registration number: ClinicalTrials.gov number, NCT05052307 (https://clinicaltrials.gov/ct2/show/NCT05052307).     

mRNA-1273 but not BNT162b2 induces antibodies against polyethylene glycol (PEG) contained in mRNA-based vaccine formulations

Two messenger RNA (mRNA)-based vaccines are widely used globally to prevent coronavirus disease 2019 (COVID-19). Both vaccine formulations contain PEGylated lipids in their composition, in the form of polyethylene glycol [PEG] 2000 dimyristoyl glycerol for mRNA-1273, and 2 [(polyethylene glycol)-2000]-N,N-ditetradecylacetamide for BNT162b2. It is known that some PEGylated drugs and products for human use which contain PEG are capable of eliciting immune responses that lead to to detectable PEG-specific antibodies in serum. In this study, we determined if any of the components of mRNA-1273 or BNT162b2 formulations elicited PEG-specific antibody responses in serum by enzyme linked immunosorbent assay (ELISA). We detected an increase in the reactivity to mRNA vaccine formulations in mRNA-1273 but not BNT162b2 vaccinees’ sera in a prime-boost dependent manner. Furthermore, we observed the same pattern of reactivity against irrelevant lipid nanoparticles from an influenza virus mRNA formulation and found that the reactivity of such antibodies correlated well with antibody levels against high and low molecular weight PEG. Using sera from participants selected based on the vaccine-associated side effects experienced after vaccination, including delayed onset, injection site or severe allergic reactions, we found no obvious association between PEG antibodies and adverse reactions. Overall, our data shows a differential induction of anti-PEG antibodies by mRNA-1273 and BNT162b2. The clinical relevance of PEG reactive antibodies induced by administration of the mRNA-1273 vaccine, and the potential interaction of these antibodies with other PEGylated drugs remains to be explored.     

Safety and efficacy of COVID-19 prime-boost vaccinations: Homologous BBIBP-CorV versus heterologous BNT162b2 boosters in BBIBP-CorV-primed individuals

BackgroundBooster vaccine doses against SARS-CoV-2 have been advocated to address evidence of waning immunity, breakthrough infection, and the emergence of immune-evasive variants. A heterologous prime-boost vaccine strategy may offer advantages over a homologous approach, but the safety and efficacy of this approach with the mRNA vaccine BNT162b2 (BNT: Pfizer) and inactivated BBIBP-CorV (BBIBT: Sinopharm) vaccines have not been studied.MethodsWe conducted a non-randomized, non-blinded phase II observational community trial across Bahrain, investigating the reactogenic and immunogenic response of participants who had previously received two doses of BBIBP, followed by a third booster dose of either BBIBP (homologous booster) or BNT (heterologous booster). Immunogenicity through serological status was determined at baseline and on the following 8th week. Reactogenicity data (safety and adverse events) were collected throughout study period, in addition to participant-led electronic journaling.Results305 participants (152 BBIBP and 153 BNT booster) were enrolled in the study, with 246 (127 BBIBP and 119 BNT booster) included in the final analysis. There was a significant increase in anti-SARS-CoV-2 antibody levels post booster administration in both groups; however, the heterologous BNT arm demonstrated a significantly larger mean increase in the level of spike (S) antigen-specific antibodies (32.7-fold increase versus 2.6, p < 0.0001) and sVNT neutralising antibodies (3.4-fold increase versus 1.8, p < 0.0001), whereas the homologous arm demonstrated a significant increase in the levels of nucleocapsid (N) antigen-specific antibodies (3.8-fold increase versus none). Non-serious adverse events (injection site pain, fever, and fatigue) were more commonly reported in the heterologous arm, but no serious adverse events occurred.ConclusionHeterologous prime-boost vaccination with the mRNA BNT162b2 (Pfizer) vaccine in those who had received two doses of inactivated virus BBIBP-CorV (Sinopharm) vaccine demonstrated a more robust immune response against SARS-CoV-2 than the homologous BBIBP booster and appears safe and well tolerated.Clinical Trial Registry Number (ClinicalTrials.gov): NCT04993560.     

Dynamics of antibody titers and cellular immunity among Japanese healthcare workers during the 6 months after receiving two doses of BNT162b2 mRNA vaccine

BackgroundThe antibody titer is known to wane within months after receiving two doses of the Pfizer-BioNTech BNT162b2 mRNA SARS-CoV-2 vaccine. However, knowledge of the cellular immune response dynamics following vaccination is limited. This study to aimed to determine antibody and cellular immune responses following vaccination, and the incidence and determinants of breakthrough infection.MethodsThis prospective cohort study a 6-month follow-up period was conducted among Japanese healthcare workers. All participants received two doses of BNT162b2 vaccine. Anti-SARS-CoV-2 antibody titers and T-cell immune responses were measured in serum samples collected at several timepoints before and after vaccination.ResultsA total of 608 participants were included in the analysis. Antibody titers were elevated 3 weeks after vaccination and waned over the remainder of the study period. T-cell immune responses showed similar dynamics. Six participants without predisposing medical conditions seroconverted from negative to positive on the IgG assay for nucleocapsid proteins, indicating breakthrough SARS-CoV-2 infection. Five of the six breakthrough infections were asymptomatic.ConclusionsBoth humoral and cellular immunity waned within 6 months after BNT162b2 vaccination. The incidence of asymptomatic breakthrough infection within 6 months after vaccination was approximately one percent.UMIN Clinical Trials Registry IDUMIN000043340.     

Immunogenicity and reactogenicity of BNT162b2 booster in BBIBP-CorV-vaccinated individuals compared with homologous BNT162b2 vaccination: Results of a pilot prospective cohort study from Lebanon

Facing new COVID-19 waves, the effectiveness of BBIBP-CorV has been noted to be low in countries whose populations were already administered two doses of the vaccine. Heterologous vaccination using ChAdOx1-S/BNT162b2 elicited higher immunogenicity compared with homologous immunization. BBIBP-CorV/BNT162b2 combination is worth testing. In this pilot prospective cohort study conducted at Makassed General Hospital, Beirut, Lebanon, from February 17, 2021, to June 30, 2021, we tested the safety and immunogenicity of a BNT162b2 booster dose in COVID-19-naïve individuals who had received two doses of the BBIBP-CorV vaccine. Heterologous booster vaccination was found to be safe and well tolerated. It was significantly associated with higher anti-spike IgG geometric mean titers compared to that after homologous BNT162b2 immunization in COVID-19-naïve individuals [(8040 BAU/mL, 95% confidence interval (CI), 4612–14 016) vs (1384 BAU/mL, 95% CI, 1063–1801), respectively, (P < 0.0001)]. In countries with limited access to mRNA vaccines and where populations have already received BBIBP-CorV, mixing BBIBP-CorV/BNT162b2 is seen to overcome the low immunogenicity induced by BBIBP-CorV alone, thus potentially providing protection against emerging variants.     

Kinetics of anti-SARS-CoV-2 antibody titer in healthy adults up to 6 months after BNT162b2 vaccination measured by two immunoassays: A prospective cohort study in Japan

BackgroundAlthough several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays.MethodsThis prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20–64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays.ResultsAmong the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively.ConclusionsTwo BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.     

One-year dynamics of antibody titers after three doses of SARS-CoV-2 BNT162b2 vaccine

BackgroundA third dose of the BNT162b2 SARS-CoV-2 vaccine leads to a significant increase in antibody levels, however, concerns regarding the long-term persistence of this response exist. We assessed the humoral response for one year following vaccination.MethodsA prospective study among immunocompetent healthcare workers (HCW) who received three doses of BNT162b2. anti-spike antibody titers were measured at six predefined timepoints, from before the second vaccine dose, and up to one year afterwards, which is 4–6 months after the third dose. HCW with a history of SARS-CoV-2 infection were excluded.ResultsSeventy-six HCW had all the six serological measurements. Antibody titers significantly increased shortly following the third vaccine dose, and while declining, remained higher from all previous measurements for up to six months.ConclusionsA third dose of BNT162b2 leads to a profound humoral response, which remains significantly higher than previous measurements, even after 6 months.     

Neutralizing antibody responses in healthcare personnel after three doses of mRNA BNT162b2 vaccine and association with baseline characteristics and past SARS-CoV-2 infection

AimTo estimate neutralizing antibody (NAb) immunity against SARS-CoV-2 in 739 healthcare personnel (HCP) vaccinated with three doses of BNT162b2 mRNA vaccine.MethodsSerum samples were collected at 3, 6, and 9 months after the second vaccine dose and at 7–55 days after the third dose. Samples were tested for NAbs against SARS-CoV-2 receptor binding domain.ResultsThe mean inhibition rates at 3, 6, and 9 months after the second dose were 86.33%, 73.38%, and 61.18%, and increased to 95.57% after the booster dose. Younger HCP and HCP with past SARS-CoV-2 infection had higher inhibition rates while there was an inverse correlation between NAb levels and comorbidities or tobacco use (p-values < 0.001). Increased NAb titers were also noticed in women (p-value = 0.033), especially at the end of the 9-month study period.ConclusionNAb levels increased considerably after a booster mRNA vaccine dose. Host factors and past SARS-CoV-2 infection influence NAb titers.