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1.
PLoS One ; 17(7): e0270801, 2022.
Article in English | MEDLINE | ID: covidwho-2021854

ABSTRACT

Studies demonstrating the waning of post-vaccination and post-infection immunity against covid-19 generally analyzed a limited range of vaccines or subsets of populations. Using Czech national health data from the beginning of the covid-19 pandemic till November 20, 2021 we estimated the risks of reinfection, breakthrough infection, hospitalization and death by a Cox regression adjusted for sex, age, vaccine type and vaccination status. Vaccine effectiveness against infection declined from 87% at 0-2 months after the second dose to 53% at 7-8 months for BNT162b2 vaccine, from 90% at 0-2 months to 65% at 7-8 months for mRNA-1273, and from 83% at 0-2 months to 55% at 5-6 months for the ChAdOx1-S. Effectiveness against hospitalization and deaths declined by about 15% and 10%, respectively, during the first 6-8 months. Boosters (third dose) returned the protection to the levels observed shortly after dose 2. In unvaccinated, previously infected individuals the protection against infection declined from 97% after 2 months to 72% at 18 months. Our results confirm the waning of vaccination-induced immunity against infection and a smaller decline in the protection against hospitalization and death. Boosting restores the original vaccine effectiveness. Post-infection immunity also decreases over time.


Subject(s)
COVID-19 , BNT162 Vaccine , COVID-19/prevention & control , Czech Republic/epidemiology , Hospitalization , Humans , Pandemics , Vaccination
2.
PLoS One ; 17(6): e0269917, 2022.
Article in English | MEDLINE | ID: covidwho-2021809

ABSTRACT

The purpose of this study was to identify factors associated with the increase in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S1) protein and neutralizing antibody titer following SARS-CoV-2 vaccination. This observational study was conducted among healthcare workers working for a private hospital group in Fukushima Prefecture, Japan. Two blood samples were obtained from each participant. The first sample was obtained before the first dose of BNT162b2 (Pfizer-BioNTech) vaccine, and a second sample was obtained approximately 6 weeks later. Immunoglobulin G (IgG) antibody against the SARS-CoV-2 spike (S1) protein, immunoglobulin M (IgM) antibody against SARS-CoV-2 N-protein, and neutralizing activity were measured using the chemiluminescent immunoassay with iFlash 3000. A total of 231 healthcare workers who agreed to participate, and were negative for anti-SARS-CoV-2 IgM antibodies at enrollment, were included in the analysis. All participants had elevated IgG antibodies and neutralizing activity above the cutoff values. A total of 174 (75.3%) and 208 (90.0%) participants experienced adverse reactions after the first and second vaccine doses, respectively. Younger age, female sex, not taking immunosuppressive or antipyretic analgesic medication regularly, a lack of local adverse reactions after the first dose, and the presence of adverse reactions (fever, muscle, and joint pain) after the second dose were associated with higher IgG antibody titers and neutralizing activity. Intake of analgesic antipyretic for adverse reactions to vaccines was not significantly associated with antibody and neutralizing activity titer production. Immune responses after vaccination may differ among individuals, and continued countermeasures to prevent SARS-CoV-2 infection are vital.


Subject(s)
Antipyretics , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Health Personnel , Humans , Immunoglobulin G , Immunoglobulin M , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination
3.
PLoS One ; 17(6): e0269885, 2022.
Article in English | MEDLINE | ID: covidwho-2021808

ABSTRACT

Monitoring the levels of IgG antibodies against the SARS-CoV-2 is important during the coronavirus disease 2019 (COVID-19) pandemic, to plan an adequate and evidence-based public health response. After this study we report that the plasma levels of IgG antibodies against SARS-CoV-2 spike protein were higher in individuals with evidence of prior infection who received at least one dose of either an mRNA-based vaccine (Comirnaty BNT162b2/Pfizer-BioNTech or Spikevax mRNA-1273/Moderna) or an adenoviral-based vaccine (Vaxzervia ChAdOx1 nCoV-19 /Oxford-Astra Zeneca) (n = 39) compared to i) unvaccinated individuals with evidence of prior infection with SARS-CoV-2 (n = 109) and ii) individuals without evidence of prior infection with SARS-CoV-2 who received one or two doses of one of the aforementioned vaccines (n = 342). Our analysis also revealed that regardless of the vaccine technology (mRNA-based and adenoviral vector-based) two doses achieved high anti- SARS-CoV-2 IgG responses. Our results indicate that vaccine-induced responses lead to higher levels of IgG antibodies compared to those produced following infection with the virus. Additionally, in agreement with previous studies, our results suggest that among individuals previously infected with SARS-CoV-2, even a single dose of a vaccine is adequate to elicit high levels of antibody response.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Cyprus , Humans , Immunoglobulin G , RNA, Messenger , SARS-CoV-2 , Seroepidemiologic Studies , Spike Glycoprotein, Coronavirus
4.
J Autoimmun ; 131: 102866, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2015569

ABSTRACT

Autoimmune systemic diseases (ASD) show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed at evaluating the seroconversion elicited by COVID-19 vaccine over the entire vaccination cycle including the booster dose. Among 478 unselected ASD patients originally evaluated at the end of the first vaccination cycle (time 1), 344 individuals were re-evaluated after a 6-month period (time 2), and 244 after the booster vaccine dose (time 3). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was assessed by measuring serum IgG-neutralizing antibody (NAb) on samples obtained at the three time points in both patients and 502 age-matched controls. In the 244 ASD group that received booster vaccine and monitored over the entire follow-up, the mean serum NAb levels (time 1, 2, and 3: 696.8 ± 52.68, 370.8 ± 41.92, and 1527 ± 74.16SD BAU/mL, respectively; p < 0.0001) were constantly lower compared to controls (p < 0.0001), but they significantly increased after the booster dose compared to the first two measurements (p < 0.0001). The percentage of patients with absent/suboptimal response to vaccine significantly decreased after the booster dose compared to the first and second evaluations (time 1, 2, and 3: from 28.2% to 46.3%, and to 7.8%, respectively; p < 0.0001). Of note, the percentage of patients with absent/suboptimal response after the booster dose was significantly higher compared to controls (19/244, 7.8% vs 1/502, 0.2%; p < 0.0001). Similarly, treatment with immune-modifiers increased the percentage of patients exhibiting absent/suboptimal response (16/122, 13.1% vs 3/122, 2.46%; p = 0.0031). Overall, the above findings indicate the usefulness of booster vaccine administration in ASD patients. Moreover, the persistence of a significantly higher percentage of individuals without effective seroconversion (7.8%), even after the booster dose, warrants for careful monitoring of NAb levels in all ASD patients to identify those with increased risk of infection. In this particularly frail patients' setting, tailored vaccination and/or therapeutic strategy are highly advisable.


Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Humans , Immunization, Secondary , Vaccination
6.
J Immunol Methods ; 506: 113293, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-2000542

ABSTRACT

BACKGROUND: Real-world population studies have shown waning immunity, over time, after receiving the two doses of the BNT162b2 COVID-19 vaccine. Studies reporting the long-term humoral response are important to drive future vaccination strategies like the introduction of the booster dose. Yet, available literature on long follow-up periods is scarce. Covidiagnostix is a multicenter study aiming to assess the antibody response in >1000 healthcare professionals (HCPs) who received the BNT162b2 vaccine. METHODS: Serum was tested at time-0 (T0), before the first dose and then at T1, T2, T3 and T4, respectively, 21, 42, 177 and 302 days after T0. Antibodies against the SARS-CoV-2 nucleocapsid-protein were measured to assess SARS-CoV-2 infections, whereas antibodies against the receptor-binding domain of the spike protein were measured to assess vaccine response. RESULTS: The antibody titer observed 10 months post-vaccination showed a decrease of approximately 80% from the peak measured at T2, yet the median titer of the seronegatives HCPs was still higher than seropositives before vaccination. We identified 12 post-vaccination infected HCPs within 6 months after receiving the first dose and another 12 post-vaccination infected HCPs between 6 and 10 months post-vaccination. CONCLUSION: Vaccination induced a humoral response which is well detectable even 10 months post-vaccination. Yet a high anti-spike serum antibody titer does not guarantee protection from infection. Differences in symptomatology between SARS-CoV-2 infections occurred within the first 6 months post-vaccination and the following 4 months, and differences in COVID-19 prevalence and vaccination coverage observed in these two time intervals were consistent with a decrease in vaccine efficacy 6 months after receiving the first dose.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Delivery of Health Care , Humans , Kinetics , SARS-CoV-2
7.
Front Immunol ; 13: 882918, 2022.
Article in English | MEDLINE | ID: covidwho-1993786

ABSTRACT

In light of the decreasing immune protection against symptomatic SARS-CoV-2 infection after initial vaccinations and the now dominant immune-evasive Omicron variants, 'booster' vaccinations are regularly performed to restore immune responses. Many individuals have received a primary heterologous prime-boost vaccination with long intervals between vaccinations, but the resulting long-term immunity and the effects of a subsequent 'booster', particularly against Omicron BA.1, have not been defined. We followed a cohort of 23 young adults, who received a primary heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, over a 7-month period and analysed how they responded to a BNT162b2 'booster'. We show that already after the primary heterologous vaccination, neutralization titers against Omicron BA.1 are recognizable but that humoral and cellular immunity wanes over the course of half a year. Residual responsive memory T cells recognized spike epitopes of the early SARS-CoV-2 B.1 strain as well as the Delta and BA.1 variants of concern (VOCs). However, the remaining antibody titers hardly neutralized these VOCs. The 'booster' vaccination was well tolerated and elicited both high antibody titers and increased memory T cell responses against SARS-CoV-2 including BA.1. Strikingly, in this young heterologously vaccinated cohort the neutralizing activity after the 'booster' was almost as potent against BA.1 as against the early B.1 strain. Our results suggest that a 'booster' after heterologous vaccination results in effective immune maturation and potent protection against the Omicron BA.1 variant in young adults.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , ChAdOx1 nCoV-19 , Humans , SARS-CoV-2 , Vaccination , Young Adult
8.
J Korean Med Sci ; 37(32): e251, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1993762

ABSTRACT

Anaphylaxis to polyethylene glycol (PEG) is rare and mainly occurs with the use of laxatives containing PEG. Recently, an increasing number of PEG allergies have been reported, particularly those related to coronavirus disease 2019 (COVID-19) vaccines. mRNA COVID-19 vaccines, such as the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines, contain PEG2000 as an excipient and are contraindicated when allergy to a vaccine component exist. We report a 55-year-old woman's history as a case of successful mRNA COVID-19 vaccination and colonoscopy after oral desensitization to PEG in a patient with PEG allergy who required both COVID-19 vaccination and colon evaluation. Allergy to PEG was diagnosed based on clinical history, skin test results, and basophil histamine release testing. Oral desensitization effectively suppressed histamine release from basophils in response to PEG stimulation, suggesting that oral desensitization using PEG-based laxatives may be an effective treatment option for patients with allergy to the substance.


Subject(s)
Anaphylaxis , COVID-19 , Anaphylaxis/chemically induced , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Colonoscopy/methods , Female , Humans , Laxatives , Middle Aged , Polyethylene Glycols/adverse effects , RNA, Messenger , Vaccination
10.
Intern Med ; 61(13): 1953-1958, 2022 Jul 01.
Article in English | MEDLINE | ID: covidwho-1993648

ABSTRACT

Objective To investigate the serum total antibody (immunoglobulin M and immunoglobulin G) titre against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor-binding domain following BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination in Japanese rheumatic disease patients undergoing immunosuppressive therapy. Methods The serum antibody titre against SARS-CoV-2 spike protein was analysed in 123 outpatients with rheumatic diseases at Kagawa University Hospital and 43 healthy volunteers who had received 2 doses of the BNT162b2 mRNA vaccine with at least 14 days elapsing since the second dose. Results The antibody titre in rheumatic disease patients was significantly lower than that in healthy subjects (p<0.0001). The antibody titres of the 41 patients who received biologics or Janus kinase inhibitors and the 47 patients who received conventional immunosuppressive agents were significantly lower than those of the 35 patients who did not receive immunosuppressive agents (p<0.0001 and p<0.0001, respectively). In addition, the mean antibody titre of the 43 patients on methotrexate was significantly lower than that of the 80 patients not on methotrexate (p=0.0017). Conclusion Immunogenicity to the BNT162b2 mRNA COVID-19 vaccine in rheumatic disease patients was found to be reduced under immunosuppressive treatment. In particular, methotrexate seems to be associated with a decreased antibody response.


Subject(s)
BNT162 Vaccine , COVID-19 , Immunogenicity, Vaccine , Rheumatic Diseases , Antibodies, Viral/blood , BNT162 Vaccine/immunology , COVID-19/prevention & control , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Neutralization Tests , Rheumatic Diseases/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
11.
Intern Med ; 61(8): 1139-1143, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1993646

ABSTRACT

Objective We evaluated the change in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody titers from three to six months after the administration of the BNT162b2 vaccine among healthcare workers. Methods A total of 337 healthcare workers who received 2 doses of the BNT162b2 vaccine were included in this study. Factors associated with SARS-CoV-2 antibody titers at three and six months and the change in SARS-CoV-2 antibody titers between three and six months after vaccine administration were analyzed using a logistic regression analysis. Results The SARS-CoV-2 antibody titer at 3 months was 4,812.1±3,762.9 AU/mL in all subjects and was lower in older workers than in younger ones. The SARS-CoV-2 antibody titer at 6 months was 1,368.9±1,412.3 AU/mL in all subjects. The SARS-CoV-2 antibody titers that were found to be high at three months were also high at six months. The change in SARS-CoV-2 antibody titers from 3 to 6 months was -68.9%±16.1%. The higher SARS-CoV-2 antibody titers at three months showed a more marked decrease from three to six months than lower titers. Conclusion This study demonstrates that SARS-CoV-2 antibody titers at three months decreased with age and were associated with the antibody titers at six months and the change in titer from three to six months. Older individuals in particular need to be aware of the declining SARS-CoV-2 antibody titers at six months after the BNT162b2 vaccine. The results of this study may provide insight into COVID-19 vaccine booster strategies.


Subject(s)
COVID-19 , Vaccines , Aged , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Health Personnel , Humans , Immunization, Secondary , Japan , Prospective Studies , RNA, Messenger , SARS-CoV-2
12.
Pediatr Rheumatol Online J ; 20(1): 64, 2022 Aug 13.
Article in English | MEDLINE | ID: covidwho-1993366

ABSTRACT

BACKGROUND: Data about safety and efficacy of the mRNA SARS-CoV-2 vaccine in adolescents with rheumatic diseases (RD) is scarce and whether these patients generate a sufficient immune response to the vaccine remains an outstanding question. OBJECTIVE: To evaluate safety and humoral and cellular immunity of the BNT162b2 vaccine in adolescents 12 to 18 years with RD and immunosuppressive treatment compared with a healthy control group. METHODS: Adolescents from 12 to 18 years with RD followed at Hospital La Paz in Madrid (n = 40) receiving the BNT162b2 mRNA vaccination were assessed 3 weeks after complete vaccination. Healthy adolescents served as controls (n = 24). Humoral response was measured by IgG antiSpike antibodies, and cellular response by the quantity of IFN-γ and IL-2 present in whole blood stimulated with SARS-CoV-2 Spike and M proteins. RESULTS: There were no differences in spike-specific humoral or cellular response between groups (median IFN-γ response to S specific protein; 528.80 pg/ml in controls vs. 398.44 in RD patients, p 0.78, and median IL-2 response in controls: 635.68 pg/ml vs. 497.30 in RD patients, p 0.22. The most frequent diagnosis was juvenile idiopathic arthritis (26/40, 65%) followed by Lupus (6/40, 15%). 60% of cases (23/40) received TNF inhibitors and 35% (14/40) methotrexate. 40% of patients (26/64) had previous SARS-CoV-2 infection, 9 in the control group and 17 in the RD patients without differences. Of note, 70% of infections were asymptomatic. A higher IFN-γ production was found in COVID-19 recovered individuals than in naive subjects in both groups (controls: median 859 pg/ml in recovered patients vs. 450 in naïve p 0.017, and RD patients: 850 in recovered vs. 278 in naïve p 0.024). No serious adverse events or flares were reported following vaccination. CONCLUSIONS: We conclude that standard of care treatment for adolescents with RD including TNF inhibitors and methotrexate did not affect the humoral and the cellular immunity to BNT162b2 mRNA vaccination compared to a healthy control group. The previous contact with SARS-CoV-2 was the most relevant factor in the immune response.


Subject(s)
COVID-19 , Rheumatic Diseases , Viral Vaccines , Adolescent , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Cellular , Interleukin-2 , Methotrexate , RNA, Messenger , Rheumatic Diseases/drug therapy , SARS-CoV-2 , Tumor Necrosis Factor Inhibitors , Viral Vaccines/genetics
14.
J Infect Dis ; 226(1): 32-37, 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1992204

ABSTRACT

Several studies reported that severe acute respiratory syndrome coronavirus-2 antibody levels change over 6 months in participants receiving the vaccination. From the enrolled 272 health care workers (HCWs), blood samples were obtained at 2, 16, and 24 weeks after the second vaccination dose. In the 267 noninfected HCWs, the neutralizing antibodies decreased by 23.9%, and the anti-spike/receptor binding domain antibody decreased by 53.8% at 24 weeks. We observed no significant difference in antibody reduction between the sexes; however, in younger individuals, there was higher antibody formation and lower reduction rates of the neutralizing antibody. In 3 HCWs with breakthrough infections, the antibody levels were relatively low just before the coronavirus disease 2019 infection. In conclusion, as antibody titers decrease over time after the second vaccination dose and HCWs with low antibody titers tend to have a high probability of breakthrough infection, an additional dose should be considered after several months. Blood samples were obtained from health care workers at 2, 16, and 24 weeks after a second vaccination dose. Antibody titers decreased over time and the participants with low antibody titers tended to have a high probability of breakthrough infection.


Subject(s)
BNT162 Vaccine , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , Health Personnel , Humans , Prospective Studies , SARS-CoV-2 , Vaccines, Synthetic , mRNA Vaccines
15.
Clin Infect Dis ; 75(Supplement_1): S51-S60, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992152

ABSTRACT

BACKGROUND: Immunization of vulnerable populations with distinct immunity often results in suboptimal immunogenicity, durability, and efficacy. METHODS: Safety and immunogenicity profiles of BNT162b2 messenger RNA coronavirus disease 2019 (COVID-19) vaccine, among people living with human immunodeficiency virus (HIV), were evaluated in 28 perinatally HIV-infected patients under antiretroviral therapy (ART) and 65 healthy controls (HCs) with no previous history of COVID-19. Thus, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific humoral and CD4+ T cell responses. Samples were collected before vaccination (baseline, day [D] 0), at the second dose (D21), and at 4 weeks (D28) and 6 months (D180) after D0. Proteomic profiles at D0 and D28 were assessed with a multiplexed proximity extension assay (Olink) on plasma samples. RESULTS: All HIV-infected patients mounted similar anti-SARS-CoV-2 humoral responses to those of HCs, albeit with lower titers of anti-trimeric S at D28 (P = .01). Only peripheral blood mononuclear cells of HIV-infected patients demonstrated at D28 an impaired ability to expand their specific (CD40L+) CD4+ T-cell populations. Similar humoral titers were maintained between the 2 groups at 6-months follow-up. We additionally correlated baseline protein levels to either humoral or cellular responses, identifying clusters of molecules involved in immune response regulation with inverse profiles between the 2 study groups. CONCLUSIONS: Responses of ART-treated HIV-infected patients, compared to those of HCs, were characterized by distinct features especially within the proteomic compartment, supporting their eligibility to an additional dose, similarly to the HC schedule.


Subject(s)
COVID-19 , HIV Infections , Adolescent , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , HIV , HIV Infections/drug therapy , Humans , Immunogenicity, Vaccine , Leukocytes, Mononuclear , Proteomics , RNA, Messenger/therapeutic use , SARS-CoV-2 , Young Adult
16.
Clin Infect Dis ; 75(Supplement_1): S11-S17, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992151

ABSTRACT

Within 2 years after the start of the coronavirus disease 2019 (COVID-19) pandemic, novel severe acute respiratory syndrome coronavirus 2 vaccines were developed, rigorously evaluated in large phase 3 trials, and administered to more than 5 billion individuals globally. However, adverse events of special interest (AESIs) have been described post-implementation, including myocarditis after receipt of messenger RNA (mRNA) vaccines and thrombosis with thrombocytopenia syndrome after receipt of adenoviral vector vaccines. AESIs are rare (<1 to 10/100 000 vaccinees) and less frequent than COVID-19 complications, though they have associated morbidity and mortality. The diversity of COVID-19 vaccine platforms (eg, mRNA, viral vector, protein) and rates of AESIs both between and within platforms (eg, higher rate of myocarditis after mRNA-1273 vs BNT162b2 vaccines) present an important opportunity to advance vaccine safety science. The International Network of Special Immunization Services has been formed with experts in vaccine safety, systems biology, and other relevant disciplines to study cases of AESIs and matched controls to uncover the pathogenesis of rare AESIs and inform vaccine development.


Subject(s)
COVID-19 , Myocarditis , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunization , Pandemics/prevention & control , RNA, Messenger
17.
Clin Infect Dis ; 75(Supplement_1): S37-S45, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1992143

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with adverse maternal and neonatal outcomes, yet uptake of SARS-CoV-2 vaccines during pregnancy and lactation has been slow. As a result, millions of pregnant and lactating women and their infants remain susceptible to the virus. METHODS: We measured spike-specific immunoglobulin G (anti-S IgG) and immunoglobulin A (anti-S IgA) in serum and breastmilk (BM) samples from 3 prospective mother-infant cohorts recruited in 2 academic medical centers. The primary aim was to determine the impact of maternal SARS-CoV-2 immunization vs infection and their timing on systemic and mucosal immunity. RESULTS: The study included 28 mothers infected with SARS-CoV-2 in late pregnancy (INF), 11 uninfected mothers who received 2 doses of the BNT162b2 vaccine in the latter half of pregnancy (VAX-P), and 12 uninfected mothers who received 2 doses of BNT162b2 during lactation. VAX dyads had significantly higher serum anti-S IgG compared to INF dyads (P < .0001), whereas INF mothers had higher BM:serum anti-S IgA ratios compared to VAX mothers (P = .0001). Median IgG placental transfer ratios were significantly higher in VAX-P compared to INF mothers (P < .0001). There was a significant positive correlation between maternal and neonatal serum anti-S IgG after vaccination (r = 0.68, P = .013), but not infection. CONCLUSIONS: BNT161b2 vaccination in late pregnancy or lactation enhances systemic immunity through serum anti-S immunoglobulin, while SARS-CoV-2 infection induces mucosal over systemic immunity more efficiently through BM immunoglobulin production. Next-generation vaccines boosting mucosal immunity could provide additional protection to the mother-infant dyad. Future studies should focus on identifying the optimal timing of primary and/or booster maternal vaccination for maximal benefit.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Female , Humans , Immunoglobulin A , Immunoglobulin G , Infant , Infant, Newborn , Lactation , Placenta , Pregnancy , Prospective Studies , SARS-CoV-2 , Vaccination
18.
Sci Rep ; 12(1): 13749, 2022 Aug 12.
Article in English | MEDLINE | ID: covidwho-1991670

ABSTRACT

We explored antibody response after first and second BNT162b2 vaccinations, to predict the need for subsequent injections in nursing home (NH) residents. 369 NH residents were tested for IgG against SARS-CoV-2 Receptor-Binding Domain (RBD-IgG) and nucleoprotein-IgG (SARS-CoV-2 IgG II Quant and SARS-CoV-2 IgG Alinity assays, Abbott Diagnostics). In NH residents with prior SARS-CoV-2 infection, the first dose elicited high RBD-IgG levels (≥ 4160 AU/mL) in 99/129 cases (76.9%), with no additional antibody gain after the second dose in 74 cases (74.7%). However, a low RBD-IgG level (< 1050 AU/mL) was observed in 28 (21.7%) residents. The persistence of nucleoprotein-IgG and a longer interval between infection and the first dose were associated with a higher RBD-IgG response (p < 0.0001 and p = 0.0013, respectively). RBD-IgG below 50 AU/mL after the first dose predicted failure to reach the antibody concentration associated with a neutralizing effect after the second dose (≥ 1050 AU/mL). The BNT162b2 vaccine elicited a strong humoral response after the first dose in a majority of NH residents with prior SARS-CoV-2 infection. However, about one quarter of these residents require a second injection. Consideration should be given to immunological monitoring in NH residents to optimize the vaccine response in this vulnerable population.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Viral , Antibody Formation , BNT162 Vaccine , COVID-19/prevention & control , Humans , Immunoglobulin G , Nucleoproteins , Nursing Homes , SARS-CoV-2 , Vaccination
19.
Nat Commun ; 13(1): 4710, 2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-1991589

ABSTRACT

Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.


Subject(s)
COVID-19 Vaccines , COVID-19 , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Humans , RNA, Messenger , SARS-CoV-2/genetics , Vaccination/adverse effects
20.
Nat Commun ; 13(1): 4800, 2022 Aug 15.
Article in English | MEDLINE | ID: covidwho-1991587

ABSTRACT

We investigated thrombocytopenic, thromboembolic and hemorrhagic events following a second dose of ChAdOx1 and BNT162b2 using a self-controlled case series analysis. We used a national prospective cohort with 2.0 million(m) adults vaccinated with two doses of ChAdOx or 1.6 m with BNT162b2. The incidence rate ratio (IRR) for idiopathic thrombocytopenic purpura (ITP) 14-20 days post-ChAdOx1 second dose was 2.14, 95% confidence interval (CI) 0.90-5.08. The incidence of ITP post-second dose ChAdOx1 was 0.59 (0.37-0.89) per 100,000 doses. No evidence of an increased risk of CVST was found for the 0-27 day risk period (IRR 0.83, 95% CI 0.16 to 4.26). However, few (≤5) events arose within this risk period. It is perhaps noteworthy that these events all clustered in the 7-13 day period (IRR 4.06, 95% CI 0.94 to 17.51). No other associations were found for second dose ChAdOx1, or any association for second dose BNT162b2 vaccination. Second dose ChAdOx1 vaccination was associated with increased borderline risks of ITP and CVST events. However, these events were rare thus providing reassurance about the safety of these vaccines. Further analyses including more cases are required to determine more precisely the risk profile for ITP and CVST after a second dose of ChAdOx1 vaccine.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thromboembolism , Adult , BNT162 Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Scotland , Thromboembolism/epidemiology , Thromboembolism/etiology , Vaccination/adverse effects
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