Administration Of Booster Research Articles

Predicting humoral responses to primary and booster SARS-CoV-2 mRNA vaccination in people living with HIV: a machine learning approach

BackgroundSARS-CoV-2 mRNA vaccines are highly immunogenic in people living with HIV (PLWH) on effective antiretroviral therapy (ART). However, whether viro-immunologic parameters or other factors affect immune responses to vaccination is debated. This study aimed to develop a machine learning-based model able to predict the humoral response to mRNA vaccines in PLWH and to assess the impact of demographic and clinical variables on antibody production over time.MethodsDifferent machine learning algorithms have been compared in the setting of a longitudinal observational study involving 497 PLWH, after primary and booster SARS-CoV-2 mRNA vaccination. Both Generalized Linear Models and non-linear Models (Tree Regression and Random Forest) were trained and tested.ResultsNon-linear algorithms showed better ability to predict vaccine-elicited humoral responses. The best-performing Random Forest model identified a few variables as more influential, within 39 clinical, demographic, and immunological factors. In particular, previous SARS-CoV-2 infection, BMI, CD4 T-cell count and CD4/CD8 ratio were positively associated with the primary cycle immunogenicity, yet their predictive value diminished with the administration of booster doses.ConclusionsIn the present work we have built a non-linear Random Forest model capable of accurately predicting humoral responses to SARS-CoV-2 mRNA vaccination, and identifying relevant factors that influence the vaccine response in PLWH. In clinical contexts, the application of this model provides promising opportunities for predicting individual vaccine responses, thus facilitating the development of vaccination strategies tailored for PLWH.

Second booster dose improves antibody neutralization against BA.1, BA.5 and BQ.1.1 in individuals previously immunized with CoronaVac plus BNT162B2 booster protocol.

SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses. To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.

Association of a coronavirus disease 2019 (COVID-19) vaccine booster with control of a COVID-19 outbreak in a long-term care facility in Switzerland, November to December 2021.

Coronavirus disease 2019 (COVID-19) outbreaks in long-term care facilities are often correlated with high case fatality rates. We describe the association of administration of an mRNA booster with the control of an outbreak. Our findings highlight the possibility of vaccine booster early in an outbreak as a promising method to mitigate the spread of infection.

Immunogenicity and Safety of Half-Dose Heterologous mRNA-1273 Booster Vaccination for Adults Primed with the CoronaVac® and ChAdOx1-S Vaccines for SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection.

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1

COVID-19 vaccines have recently been updated to specifically encode or contain the spike protein of the SARS-CoV-2 XBB.1.5 subvariant, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine booster (XBB.1.5 MV) to previously uninfected individuals boosted serum virus-neutralizing antibodies significantly against not only XBB.1.5 (27.0-fold increase) and EG.5.1 (27.6-fold increase) but also key emerging viruses such as HV.1, HK.3, JD.1.1, and JN.1 (13.3- to 27.4-fold increase). Individuals previously infected by an Omicron subvariant had the highest overall serum neutralizing titers (ID50 1,504-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as observed with the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines.

Intradermal Fractional ChAdOx1 nCoV-19 Booster Vaccine Induces Memory T Cells: A Follow-Up Study.

The administration of viral vector and mRNA vaccine booster effectively induces humoral and cellular immune responses. Effector T cell responses after fractional intradermal (ID) vaccination are comparable to those after intramuscular (IM) boosters. Here, we quantified T cell responses after booster vaccination. ChAdOx1 nCoV-19 vaccination induced higher numbers of S1-specific CD8+ memory T cells, consistent with the antibody responses. Effector memory T cell phenotypes elicited by mRNA vaccination showed a similar trend to those elicited by the viral vector vaccine booster. Three months post-vaccination, cytokine responses remained detectable, confirming effector T cell responses induced by both vaccines. The ID fractional dose of ChAdOx1 nCoV-19 elicited higher effector CD8+ T cell responses than IM vaccination. This study confirmed that an ID dose-reduction vaccination strategy effectively stimulates effector memory T cell responses. ID injection could be an improved approach for effective vaccination programs.

Durability of humoral and cellular immunity six months after the BNT162b2 bivalent booster.

Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Blood samples were collected before the administration of the bivalent booster from Pfizer-BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma from T cells in response to an in vitro SARS-CoV-2 stimulation. A substantial waning of neutralizing antibodies was observed after 6 months (23.1-fold decrease), especially considering the XBB.1.5 subvariant. The estimated T1/2 of neutralizing antibodies was 16.1 days (95% CI = 10.2-38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.95 vs. 0.41 UI/L, p = 0.0083). A significant waning of the humoral and cellular response was observed after 6 months. These data can also help competent national authorities in their recommendation regarding the administration of an additional booster.

Significant increase in anti-SARS-CoV-2 antibodies after administration of heterologous mRNA-based vaccine booster in individuals receiving two doses of inactivated COVID-19 vaccine: A single-center study in healthcare workers in Jakarta, Indonesia

BackgroundVaccine plays an important role in breaking SARS-CoV-2 transmission and accelerating the path to pandemic recovery. Currently, there is still limited data on heterologous COVID-19 booster vaccination efficacy and effectiveness in Indonesia. MethodsAntibody response was retrospectively analyzed from 156 serum collected from healthcare workers that have received mRNA-1273 vaccine as the booster against SARS-CoV-2. These individuals had previously received the full two doses of inactivated anti-SARS-CoV-2 vaccine. Serological analysis was performed to measure total antibody, as well as IgA and IgG antibodies specific to spike (S) protein using ECLIA and ELISA methods. ResultsA significant increase in total, IgA, and IgG antibody titers was reported in vaccine receiving a third heterologous booster dose of mRNA-based COVID-19 vaccine following two doses of inactivated type. ConclusionThe third heterologous booster dose of vaccine may be beneficial to individuals with or without previous history of SARS-CoV-2 infection.

Simultaneous administration of mRNA COVID-19 bivalent booster and influenza vaccines

The U.S. Food and Drug Administration authorized use of mRNA COVID-19 bivalent booster vaccines on August 31, 2022. Currently, CDC’s clinical guidance states that COVID-19 and other vaccines may be administered simultaneously. At time of authorization and recommendations, limited data existed describing simultaneous administration of COVID-19 bivalent booster and other vaccines. We describe simultaneous influenza and mRNA COVID-19 bivalent booster vaccine administration between August 31–December 31, 2022, among persons aged ≥6 months in the Vaccine Safety Datalink (VSD) by COVID-19 bivalent booster vaccine type, influenza vaccine type, age group, sex, and race and ethnicity. Of 2,301,876 persons who received a COVID-19 bivalent booster vaccine, 737,992 (32.1%) received simultaneous influenza vaccine, majority were female (53.1%), aged ≥18 years (91.4%), and non-Hispanic White (55.7%). These findings can inform future VSD studies on simultaneous influenza and COVID-19 bivalent booster vaccine safety and coverage, which may have implications for immunization service delivery.

Protective Anti-HBs Antibodies and Response to a Booster Dose in Medical Students Vaccinated at Childhood.

The immune system in humans is regulated by the circadian rhythm. Published studies have reported that the time of vaccination is associated with the immune response to vaccine for some pathogens. Our study aimed to evaluate the association between time of dose administration of challenge HBV vaccine and seroconversion for anti-HBs in medical students vaccinated at birth who were found to be unprotected at pre-training screening. Humoral protection for HBV was assessed in 885 medical students vaccinated during childhood. In total, 359 (41.0%) of them showed anti-HBs titer < 10 UI/mL and received a challenge dose of HBV vaccine followed by post-vaccination screening 30-60 days later. The challenge dose elicited a protective immune response (anti-HBs IgG titer > 10 UI/mL) in 295 (83.8%) individuals. Seroconversion was significantly associated with female gender and time of vaccination after controlling for age group and nationality at logistic regression analysis. Students who received the booster dose in the morning had a higher response rate than those who received the vaccine in the afternoon (OR 1.93; 95% C.I. 1.047-3.56: p < 0.05). This finding suggests that morning administration of the HBV booster may result in a better immune response in susceptible individuals.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults

The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n=87). In parallel, cellular immunity (n=45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p<0.0001; Geometric mean titer p=0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ Tlymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

In-depth characterization of long-term humoral and cellular immune responses to COVID-19m-RNA vaccination in multiple sclerosis patients treated with teriflunomide or alemtuzumab

The impact of disease-modifying therapies on the efficacy to mount appropriate immune responses to COVID-19 vaccination in patients with multiple sclerosis (MS) is currently under investigation. To characterize long-term humoral and cellular immunity in mRNA-COVID-19 MS vaccinees treated with teriflunomide or alemtuzumab. We prospectively measured SARS-COV-2 IgG, memory B-cells specific for SARS-CoV-2 RBD, and memory T-cells secreting IFN-γ and/or IL-2, in MS patients vaccinated with BNT162b2-COVID-19 vaccine before, 1, 3 and 6 months after the second vaccine dose, and 3-6 months following vaccine booster. Patients were either untreated (N=31, 21 females), under treatment with teriflunomide (N=30, 23 females, median treatment duration 3.7 years, range 1.5-7.0 years), or under treatment with alemtuzumab (N=12, 9 females, median time from last dosing 15.9 months, range 1.8-28.7 months). None of the patients had clinical SARS-CoV-2 or immune evidence for prior infection. Spike IgG titers were similar between untreated, teriflunomide and alemtuzumab treated MS patients both at 1 month (median 1320.7, 25-75 IQR 850.9-3152.8vs. median 901.7, 25-75 IQR 618.5-1495.8, vs. median 1291.9, 25-75 IQR 590.8-2950.9, BAU/ml, respectively), at 3 months (median 1388.8, 25-75 1064.6-2347.6vs. median 1164.3 25-75 IQR 726.4-1399.6, vs. median 837.2, 25-75 IQR 739.4-1868.5 BAU/ml, respectively), and at 6 months (median 437.0, 25-75 206.1-1161.3vs. median 494.3, 25-75 IQR 214.6-716.5, vs. median 176.3, 25-75 IQR 72.3-328.8 BAU/ml, respectively) after the second vaccine dose. Specific SARS-CoV-2 memory B cells were detected in 41.9%, 40.0% and 41.7% of subjects at 1 month, in 32.3%, 43.3% and 25% at 3 months, and in 32.3%, 40.0%, 33.3% at 6 months following vaccination in untreated, teriflunomide treated and alemtuzumab treated MS patients, respectively. Specific SARS-CoV-2 memory T cells were found in 48.4%, 46.7% and 41.7 at 1 month, in 41.9%, 56.7% and 41.7% at 3 months, and in 38.7%, 50.0%, and 41.7% at 6 months, of untreated, teriflunomide-treated and alemtuzumab -treated MS patients, respectively. Administration of a third vaccine booster significantly increased both humoral and cellular responses in all patients. MS patients treated with teriflunomide or alemtuzumab achieved effective humoral and cellular immune responses up to 6 months following second COVID-19 vaccination. Immune responses were reinforced following the third vaccine booster.

Stimulating immunoglobulin response by intramuscular delivery of exopolysaccharides-adjuvanted mannheimiosis vaccine in goats.

Pneumonic mannheimiosis (PM) is a common respiratory bacterial disease among small ruminants. Despite numerous management methods, vaccination remains a suitable strategy to combat or reduce PM in goats and sheep. Thus, a study was conducted in Malaysia to evaluate the immunogenicity of exopolysaccharide-adjuvanted Mannheimia haemolytica A2 vaccine (EPS-MHA2) under laboratory and field conditions for its potential use as an efficient vaccine against PM. This study induced immunoglobulin (Ig) responses following intramuscular (IM) delivery of the EPS-MHA2 vaccine on 12 goats for about 7 months. Goats were divided into three groups, with three goats per group, and they were vaccinated intramuscularly as follows: Group 1 was vaccinated with an adjuvanted vaccine prepared from formalin-killed M. haemolytica serotypes A2 and EPS excipient; Group 2 was vaccinated with formalin-killed M. haemolytica seed only, whereas Group 3 was injected with phosphate-buffered saline (PBS) as the negative control. Measures of specific immunity included serum IgM, IgG, and IgA as well as bronchoalveolar lavage fluid secretory IgA and the size and number of the bronchus-associated lymphoid tissue (BALT). From the 1st day of vaccination, Groups 1 and 2 showed a significant (p < 0.05) increase in serum IgM, IgG, and IgA levels. However, the antibodies started to decline 5-week post-vaccination, indicating that the booster dose was necessary. On the second exposure to the same vaccine (booster), the level of antibodies showed a significant increase (p < 0.05), particularly IgG. All groups were challenged intratracheally by virulent MHA2 2 weeks after the decline of second antibodies on the administration of booster. All goats were euthanatized and necropsied 4-week post-challenge. The number and size of the BALT in Group 1 goats significantly increased compared with those in Group 2 and the unvaccinated control. Bacteriological parameters were evaluated, in which MHA2 was reisolated successfully from lung samples in Group 3. The IgA level produced by the group vaccinated with EPS-MHA2 was significantly (p < 0.001) higher than that the MHA2 vaccine and PBS groups. All data obtained were analyzed statistically using a one-way analysis of variance. The results indicate that IM injection of EPS-MHA2 vaccine significantly enhanced the immune response against MHA2. Therefore, the addition of EPS to MHA2 (EPS-MHA2 vaccine) can effectively protect goats from lethal mannheimiosis infection. Factors such as the ideal concentration of EPS should be further studied to verify its application potential as a vaccine adjuvant, and the extraction of EPS from different microalgae species should be further investigated. This study showed a novel and exciting set of data and a vaccination system, in which the suppressive effects of mannheimiosis may be further investigated.

Heterologous Booster Dose with CORBEVAX following Primary Vaccination with COVISHIELD Enhances Protection against SARS-CoV-2.

Despite effective vaccination programs, waning immunity in the vaccinated populations and the emergence of variants of concern posed a risk of breakthrough infections. A booster dose was demonstrated to provide substantially increased protection against symptomatic disease and hospitalization. We aimed to evaluate immune memory and the efficacy of reducing the rate of SARS-CoV-2 infection post heterologous booster with CORBEVAX after primary vaccination with two doses of COVISHIELD. SARS-CoV-2 S1/S2 spike IgG and RBD-specific antibody responses were elicited with both booster vaccines, with a greater response in individuals receiving heterologous booster. T and B memory responses were increased with booster dose, whereas B memory needed a longer duration to develop in individuals who received a homologous booster (90 days) in comparison to a heterologous booster (30 days). RBD-specific B memory and antibody-secreting (non-memory) B lymphocytes were enhanced with both boosters; however, the duration of response was longer with the heterologous booster compared to the homologous, indicating greater protection with the heterologous booster. The rate of infection 14 days after administration of the heterologous booster was comparatively lower than that of the homologous booster, with the symptoms being much less or asymptomatic.

Reactogenicity to the mRNA-1273 Booster According to Previous mRNA COVID-19 Vaccination.

The objective of this study was to assess the local and systemic adverse reactions after the administration of a COVID-19 mRNA-1273 booster between December 2021 and February 2022 by comparing the type of mRNA vaccine used as primary series (mRNA-1273 or BNT162b2) and homologous versus heterologous booster in health care workers (HCW). A cross-sectional study was performed in HCW at a tertiary hospital in Barcelona, Spain. A total of 17% of booster recipients responded to the questionnaire. The frequency of reactogenicity after the mRNA-1273 booster (88.5%) was similar to the mRNA-1273 primary doses (85.8%), and higher than the BNT162b2 primary doses (71.1%). The reactogenicity was similar after receiving a heterologous booster compared to a homologous booster (88.0% vs. 90.2%, p = 0.3), and no statistically significant differences were identified in any local or systemic reactions. A higher frequency of medical leave was identified in the homologous booster dose group vs. the heterologous booster dose group (AOR 1.45; 95% CI: 1.00–2.07; p = 0.045). Our findings could be helpful in improving vaccine confidence toward heterologous combinations in the general population and in health care workers.

Reactogenicity of Simultaneous COVID-19 mRNA Booster and Influenza Vaccination in the US

COVID-19 and seasonal influenza vaccines are essential in preventing respiratory infections and their potentially severe complications. Simultaneous administration of vaccines is efficient and may improve coverage with each vaccine. However, the safety of simultaneous administration of COVID-19 and influenza vaccines has not been well described. To evaluate adverse events and health impacts associated with simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines in the US population. In this retrospective cohort study, self-reported vaccine data were collected on days 0 to 7 after vaccination from September 22, 2021, through May 1, 2022, through v-safe, a voluntary smartphone-based monitoring system established by the Centers for Disease Control and Prevention. Participants were persons who voluntarily registered in v-safe following COVID-19 vaccination. Receipt of simultaneously administered COVID-19 mRNA booster and seasonal influenza vaccines or COVID-19 mRNA booster alone. Local injection site and systemic reactions (eg, fatigue, headache, and myalgia) and health impacts reported by v-safe respondents in the week following COVID-19 mRNA booster vaccination. Adjusted odds ratios (aORs) were estimated for simultaneous administration compared with booster dose alone, controlling for sex, age, and week of vaccination. Of a total of 981 099 persons aged 12 years or older registered with v-safe, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was reported by 92 023 (9.4%) v-safe respondents; of these respondents, 54 926 (59.7%) were female, 36 234 (39.4%) were male, and sex was unknown for 863 (0.9%). In the week following vaccination, any systemic reactions were reported by 36 144 (58.9%) of 61 390 respondents who simultaneously received Pfizer-BioNTech booster and influenza vaccines and 21 027 (68.6%) of 30633 respondents who simultaneously received Moderna booster and influenza vaccines. Respondents who simultaneously received influenza and Pfizer-BioNTech booster vaccines (aOR, 1.08; 95% CI, 1.06-1.10) or influenza and Moderna booster vaccines (aOR, 1.11; 95% CI, 1.08-1.14) were slightly more likely to report any systemic reaction in the week following simultaneous vaccination than respondents who received only a COVID-19 mRNA vaccine booster. In this study, compared with administration of COVID-19 mRNA booster vaccines alone, simultaneous administration of COVID-19 mRNA booster and seasonal influenza vaccines was associated with significant increases in reports of systemic reactions during days 0 to 7 following vaccination. These results may help better characterize the outcomes associated with simultaneously administered COVID-19 booster and influenza vaccines in the US population.

Reactogenicity and Concomitant Administration of the COVID-19 Booster and Influenza Vaccine

Reactogenicity and Concomitant Administration of the COVID-19 Booster and Influenza Vaccine

Third trimester messenger RNA COVID-19 booster vaccination upsurge maternal and neonatal SARS-CoV-2 immunoglobulin G antibody levels at birth

ObjectiveBNT162b2 messenger RNA (mRNA) COVID-19 vaccine administered during pregnancy was found to produce a strong maternal immunoglobulin (IgG) response which crosses the placenta to the newborn. Our aim was to evaluate maternal and neonatal SARS-CoV-2 IgG antibody levels at birth, following a COVID-19 booster vaccine during the third trimester. Study designA prospective cohort study including women admitted to delivery ward at least 7 days after their BNT162b2 (Pfizer/BioNTech) booster vaccination without a prior clinical COVID-19 infection. SARS-CoV-2 IgG antibodies levels were measured in maternal blood upon admission to delivery and in the umbilical blood within 30 min following delivery. The correlation between antibody titers, feto-maternal characteristics, maternal side effects following vaccination, and time interval from vaccination to delivery were analyzed. ResultsBetween September to November 2021, high antibody levels were measured in all 102 women and 93 neonatal blood samples, at a mean ± standard deviation duration of 7.0 ± 2.9 weeks after the third vaccine. We found positive correlation between maternal and neonatal antibodies (r = 0.73, 95% confidence interval [CI] 0.61 to 0.81, p < 0.001), with neonatal titers approximately 1.4 times higher compared to maternal titers. In the multivariable analysis maternal antibody levels dropped by −7.2% (95% CI −12.0 to −2.3%, p = 0.005) for each week that passed since the receipt of the third vaccine dose. In contrary, systemic side effects after the third vaccine were associated with higher maternal antibody levels of 52.0% (95% CI 4.7 to 120.8%, p = 0.028). Also, for each 1 unit increase in maternal body mass index, maternal antibody levels increased by 3.6% (95% CI 0.4 to 6.9%, p = 0.025). ConclusionsBNT162b2 mRNA COVID-19 booster dose during the third trimester of pregnancy was associated with strong maternal and neonatal responses as reflected by maternal and neonatal SARS-CoV-2 IgG antibody levels measured at birth. These findings support the administration of the COVID-19 booster to pregnant women to restore maternal and neonatal protection during the ongoing pandemic.

Impact of BNT162b2 primary vaccination and homologous booster on anti-SARS-CoV-2 IgA antibodies in baseline seronegative healthcare workers.

We investigated here the response of anti-SARS-CoV-2 IgA antibodies to BNT162b2 primary vaccination followed by administration of a homologous booster dose in baseline seronegative healthcare workers. The study population included 69 healthy recipients of primary BNT162b2 vaccination (two doses) followed by administration of a single homologous booster after 8months. Blood samples were collected throughout the study, starting before the first vaccine dose, up to 1month after the booster. The serum levels of anti-SARS-CoV-2 IgA were assayed with Euroimmun Anti-SARS-CoV-2 spike S1 ELISA IgA. A first peak of serum anti-SARS-CoV-2 IgA was seen 1month after the second BNT162b2 dose, after which values gradually declined, with stabilization after 6months. The BNT162b2 booster (third dose) elicited a second peak, comparable to that observed 1month after the second dose (p=0.100). Highly significant correlation was found between pre- and post-booster anti-SARS-CoV-2 IgA serum values (r=0.41; p<0.001), whilst no significant correlation was observed with age (r=0.10; p=0.416) or sex (r=0.04; p=0.729). The rate of SARS-CoV-2 IgA seropositive recipients increased from 0% before vaccination to 80 and 97% after the first and second vaccine dose, but then declined becoming 74% at 3months and 54% at 6months, respectively, after which stabilization was reached. The BNT162b2 booster dose restored the seropositivity rate to 99%. These results support the suggestion that vaccine boosters may be advisable after 3months from primary vaccination to restore IgA to protective levels, especially in those at higher risk of SARS-CoV-2 infection and complications.

Effect of BNT162b2 booster dose on anti-SARS-CoV-2 spike trimeric IgG antibodies in seronegative individuals.

We provide here an updated analysis of an ongoing serosurveillance study, presenting data on the effect of a third dose of Pfizer/BioNTech BNT162b2 vaccine on serum anti-SARS-CoV-2 IgG antibodies. We tested baseline SARS-CoV-2 seronegative healthcare workers undergoing primary vaccination with the mRNA-based COVID-19 Comirnaty vaccine, followed by administration of homologous vaccine booster (third dose). Venous blood was collected before either dose of primary vaccination, at 1, 3 and 6months afterwards, as well as before and 1month after receiving the vaccine booster. The serum concentration of anti-SARS-CoV-2 IgG was assayed with DiaSorin Trimeric spike IgG immunoassay. The final study population included 53 SARS-CoV-2 seronegative healthcare workers (median age 46years; 60% females). A first peak of anti-SARS-CoV-2 spike trimeric IgG values was reached 1month after completing primary vaccination, after which the levels gradually declined until before receiving the vaccine booster. A second peak of anti-SARS-CoV-2 spike trimeric IgG concentration was observed 1month after receiving the vaccine booster dose (8,700kBAU/L), which was 39-fold higher than before receiving the vaccine booster (221kBAU/L; p<0.001), but was also nearly threefold higher compared to values seen at the first peak (2,990kBAU/L; p<0.001). The rate of subjects with protective anti-SARS-CoV-2 spike trimeric IgG values (i.e.,>264kBAU/L) increased from 47.2% to 100% after 1month from vaccine booster. These results support current policies fostering COVID-19 vaccine boosters to reinforce humoral immunity against SARS-CoV-2.