Project description:BackgroundTo optimise the use of available SARS-CoV-2 vaccines, some advocate delaying second vaccination for individuals infected within six months. We studied whether post-vaccination immune response is equally potent in individuals infected over six months prior to vaccination.MethodsWe tested serum IgG binding to SARS-CoV-2 spike protein and neutralising capacity in 110 healthcare workers, before and after both BNT162b2 messenger RNA (mRNA) vaccinations. We compared outcomes between participants with more recent infection (n = 18, median two months, IQR 2-3), with infection-vaccination interval over six months (n = 19, median nine months, IQR 9-10), and to those not previously infected (n = 73).FindingsBoth recently and earlier infected participants showed comparable humoral immune responses after a single mRNA vaccination, while exceeding those of previously uninfected persons after two vaccinations with 2.5 fold (p = 0.003) and 3.4 fold (p < 0.001) for binding antibody levels, and 6.4 and 7.2 fold for neutralisation titres, respectively (both p < 0.001). The second vaccine dose yielded no further substantial improvement of the humoral response in the previously infected participants (0.97 fold, p = 0.92), while it was associated with a 4 fold increase in antibody binding levels and 18 fold increase in neutralisation titres in previously uninfected participants (both p < 0.001). Adjustment for potential confounding of sex and age did not affect these findings.InterpretationDelaying the second vaccination in individuals infected up to ten months prior may constitute a more efficient use of limited vaccine supplies.FundingNetherlands Organization for Health Research and Development ZonMw; Corona Research Fund Amsterdam UMC; Bill & Melinda Gates Foundation.
Project description:As of 2021 November 29, booster vaccination against SARS-CoV-2 infection has been recommended for all individuals aged 18 years and older in the United States. A key reason for this recommendation is the expectation that a booster vaccine dose can alleviate observed waning of vaccine effectiveness (VE). Although initial reports of booster effectiveness have been positive, the level of protection from booster vaccination is unclear. We conducted two studies to assess the impact of booster vaccination, with BNT162b2 or mRNA-1273, on the incidence of SARS-CoV-2 infection between August and December 2021. We first compared SARS-CoV-2 infection incidence in cohorts of 3-dose vaccine recipients to incidence in matched cohorts of 2-dose vaccine recipients (cohort size = 24,539 for BNT162b2 and 14,004 for mRNA-1273). Additionally, we applied a test-negative study design to compare the level of protection against symptomatic infection in 3-dose recipients to that observed in recent 2-dose primary vaccine series recipients. The 3-dose recipients experienced a significantly lower incidence rate of SARS-CoV-2 infection than the matched 2-dose cohorts (BNT162b2 Incidence Rate Ratio: 0.11, 95% CI: 0.09 to 0.13 and mRNA-1273 IRR: 0.11, 95% CI: 0.08 to 0.15). Results from the test-negative study showed the third vaccine dose mitigated waning of VE, with the risk of symptomatic infection in 3-dose recipients being comparable to that observed 7 to 73 days after the primary vaccine series. These results show that 3-dose vaccine regimens with BNT162b2 or mRNA-1273 are effective at reducing SARS-CoV-2 infection and support the widespread administration of booster vaccine doses.
Project description:Study questionDoes the immune response to coronavirus disease 2019 (COVID-19) infection or the BNT162b2 mRNA vaccine involve the ovarian follicle, and does it affect its function?Summary answerWe were able to demonstrate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG in follicular fluid (FF) from both infected and vaccinated IVF patients, with no evidence for compromised follicular function.What is known alreadyNo research data are available yet.Study design, size, durationThis is a cohort study, composed of 32 consecutive IVF patients, either infected with COVID-19, vaccinated or non-exposed, conducted between 1 February and 10 March 2021 in a single university hospital-based IVF clinic.Participants/materials, setting, methodsA consecutive sample of female consenting patients undergoing oocyte retrieval was recruited and assigned to one of the three study groups: recovering from confirmed COVID-19 (n = 9); vaccinated (n = 9); and uninfected, non-vaccinated controls (n = 14). Serum and FF samples were taken and analyzed for anti-COVID IgG as well as estrogen, progesterone and heparan sulfate proteoglycan 2 concentration, as well as the number and maturity of aspirated oocytes and day of trigger estrogen and progesterone measurements. Main outcome measures were follicular function, including steroidogenesis, follicular response to the LH/hCG trigger, and oocyte quality biomarkers.Main results and the role of chanceBoth COVID-19 and the vaccine elicited anti-COVID IgG antibodies that were detected in the FF at levels proportional to the IgG serum concentration. No differences between the three groups were detected in any of the surrogate parameters for ovarian follicle quality.Limitations, reasons for cautionThis is a small study, comprising a mixed fertile and infertile population, and its conclusions should be supported and validated by larger studies.Wider implications of the findingsThis is the first study to examine the impact of SARS-Cov-2 infection and COVID-19 vaccination on ovarian function and these early findings suggest no measurable detrimental effect on function of the ovarian follicle.Study funding/competing interest(s)The study was funded out of an internal budget. There are no conflicts of interest for any of the authors.Trial registration numberCinicalTrials.gov registry number NCT04822012.
Project description:Only limited data are available regarding the immunogenicity of the BNT162b2 mRNA vaccine in HIV-1+ patients. Therefore, we investigated the humoral immune response after BNT162b2-mRNA vaccination or SARS-CoV-2 infection in HIV-1+ patients on antiretroviral therapy compared to HIV-1-uninfected subjects. Serum and saliva samples were analysed by SARS-CoV-2 spike-specific IgG and IgA ELISAs and a surrogate neutralization assay. While all subjects developed anti-spike IgG and IgA and neutralizing antibodies in serum after two doses of BNT162b2 mRNA vaccine, the HIV-1+ subjects displayed significantly lower neutralizing capacity and anti-spike IgA in serum compared to HIV-1-uninfected subjects. Serum levels of anti-spike IgG and neutralizing activity were significantly higher in vaccinees compared to SARS-CoV-2 convalescents irrespective of HIV-1 status. Among SARS-CoV-2 convalescents, there was no significant difference in spike-specific antibody response between HIV-1+ and uninfected subjects. In saliva, anti-spike IgG and IgA antibodies were detected both in vaccinees and convalescents, albeit at lower frequencies compared to the serum and only rarely with detectable neutralizing activity. In summary, our study demonstrates that the BNT162b2 mRNA vaccine induces SARS-CoV-2-specific antibodies in HIV-1-infected patients on antiretroviral therapy, however, lower vaccine induced neutralization activity indicates a lower functionality of the humoral vaccine response in HIV-1+ patients.
Project description:BackgroundImmunocompromised individuals have been excluded from landmark studies of messenger RNA vaccinations for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). In such patients, the response to vaccination may be blunted and may wane more quickly compared with immunocompetent patients. We studied the factors associated with decreased antibody response to SARS-CoV-2 vaccination and risk factors for subsequent breakthrough infections in liver transplant (LT) patients undergoing coronavirus disease 2019 vaccination with at least 2 doses of messenger RNA vaccine from April 28, 2021, to April 28, 2022.MethodsAll LT recipients received at least 2 doses of the BNT162b2 (Pfizer BioNTech) vaccine 21 d apart. We measured the antibody response against the SARS-CoV-2 spike protein using the Roche Elecsys immunoassay to the receptor-binding domain of the SARS-CoV-2 spike protein, and the presence of neutralizing antibodies was measured by the surrogate virus neutralization test (cPass) before first and second doses of vaccination and also between 2 and 3 mo after the second dose of vaccination.ResultsNinety-three LT recipients who received 2 doses of BNT162b2 were included in the analysis. The mean time from LT was 110 ± 154 mo. After 2-dose vaccination, 38.7% of LT recipients (36/93) were vaccine nonresponders on the cPass assay compared with 20.4% (19/93) on the Roche S assay. On multivariable analysis, increased age and increased tacrolimus trough were found to be associated with poor neutralizing antibody response (P = 0.038 and 0.022, respectively). The use of antimetabolite therapy in conjunction with tacrolimus approached statistical significance (odds ratio 0.21; 95% confidence interval, 0.180-3.72; P = 0.062). Breakthrough infection occurred in 18 of 88 LT recipients (20.4%). Female gender was independently associated with breakthrough infections (P < 0.001).ConclusionsAmong LT recipients, older age and higher tacrolimus trough levels were associated with poorer immune response to 2-dose SARS-CoV-2 vaccination. Further studies are needed to assess variables associated with breakthrough infections and, hence, who should be prioritized for booster vaccination.
Project description:BackgroundInflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC), are associated with higher thrombotic risk and enhanced thrombin generation (TG) in adults. Despite encouraging data reporting vaccine safety and low IBD flare rates in adults with IBD, vaccine hesitancy was demonstrated to be high in families of children with IBD. We aimed to find out whether TG is increased in children with IBD as compared to healthy controls and whether TG parameters show significant changes following SARS-CoV-2 mRNA vaccination.Patients and methodsIn this observational case-control study, 38 children with IBD (CD:18, UC: 20) aged 12-18 years and 62 healthy age-and sex-matched children were enrolled. Blood was collected before the first dose and 2-6 weeks after the second dose of BNT162b2 (Pfizer-BioNTech) mRNA vaccine dose. Blood cell counts, fibrinogen, inflammatory markers (hsCRP, ferritin), anti-SARS-CoV-2 antibody levels were investigated, TG assay was carried-out using platelet-poor plasma. Detailed clinical parameters including disease activity scores (PUCAI, PCDAI) were registered pre-and post- vaccination. A guided questionnaire was used to collect data on adverse reactions (AEs) post- vaccination.ResultsBaseline TG parameters did not differ between patients and controls. Endogenous thrombin potential showed a significant positive correlation with markers of inflammation and with PCDAI. Inflammatory parameters and TG did not increase in patients and controls post-vaccination. Vaccination significantly increased antibody levels in all three investigated groups, but post-vaccination anti-SARS-CoV-2 S IgG/IgM levels were below the 5th percentile value of healthy children in more than one third of patients. Those receiving TNFα inhibitor therapy presented significantly lower SARS-CoV-2 S IgG/IgM levels as compared to patients on other immunosuppressive regimens. Systemic AEs did not differ between patients and controls while lower rate of local symptoms was found post-vaccination in children with IBD. Only 2 IBD flares were detected 2-6 weeks after the second dose of vaccination.ConclusionOur study is the first to support the safety and efficacy of anti-SARS-CoV-2 BNT162b2 vaccination in children with IBD with detailed pre-and post-vaccination laboratory data including TG. Results of this study may further increase confidence and reduce vaccine hesitancy in caretakers of pediatric IBD patients.
Project description:The immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined >50,000 positive cases and >110,000 contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts' socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.
Project description:BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1-2 weeks after vaccination or 15-59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651-5583), 6228 (3254-9203) and 7651 (4479-10,823) AU/mL in 35-44, 45-54, 55-70 yrs, respectively, compared with the 18-34 yrs group. In females, the median levels were higher by 2823 (859-4787), 5024 (3122-6926) in individuals with VSE, and 9971 (5158-14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.