Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years.
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ABSTRACT:
SUBMITTER: Romero-Olmedo AJ
PROVIDER: S-EPMC8986166 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
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Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years.
Romero-Olmedo Addi J AJ Schulz Axel Ronald AR Hochstätter Svenja S Gupta Dennis Das DD Hirseland Heike H Staudenraus Daniel D Camara Bärbel B Volland Kirsten K Hefter Véronique V Sapre Siddhesh S Krähling Verena V Müller-Kräuter Helena H Chung Ho-Ryun HR Mei Henrik E HE Keller Christian C Lohoff Michael M
The Lancet. Infectious diseases 20220406 5
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Project description:Clinical data showed sex variability in the immune response to influenza vaccination, this study aimed to investigate differentially expressed genes that contribute to sex-bias immune responses to quadrivalent inactivated influenza vaccines (QIVs) in older subjects. A cohort of 60 healthy older adults aged 60 to 80 years old were vaccinated with quadrivalent inactivated influenza vaccines (QIVs), and gene expression was analyzed at Day 0 pre-vaccination, Day 3, Day 28 and Day 180 post-vaccination. Sexual dimorphism of humoral immunity was analyzed by HAI assay, and the correlation of gene expression patterns of two sex groups with humoral immune response to vaccination was analyzed. The differentially expressed genes involved in type I interferon signaling pathway and complement activation of classical pathway were upregulated within 3 days post-vaccination in females. At Day 28 after immunization, the immune response showed a man-bias pattern associated with the regulation of protein processing and complement activation of classical pathway. A list of differentially expressed genes associated with variant responses to influenza vaccination between women and men were identified by biology-driven clustering. Old women have a greater immune response to QIVs but rapid decline of antibody levels, while old men have the advantages to sustain a durable response to influenza vaccination. In addition, we identified genes that may contribute to the sex variations toward influenza vaccination in the aged. Our findings highlight the importance of developing personalized seasonal influenza vaccines.
2020-11-09 | GSE151558 | GEO
Project description:The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations.
| S-EPMC8757952 | biostudies-literature
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| S-EPMC10853639 | biostudies-literature
Project description:BackgroundThe emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019.MethodsIn an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2 + 15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2 + 30 μg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants.ResultsA total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%).ConclusionsThe candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).
| S-EPMC9933930 | biostudies-literature
Project description:ObjectivesThe oldest-old (aged ≥80 years) are the fastest growing population segment and age is related to cognitive impairment. We aimed to estimate the association between cognitive impairment and all-cause mortality, in addition to the relationship with different cognitive subdomains among the oldest-old in China.MethodsWe analyzed 25,285 participants recruited from 22 out of 30 provinces in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2008, with mortality follow-up until 2014. Cognitive function was measured by the Chinese-version 30-item Mini-Mental State Examination (MMSE), classified as no (MMSE score: 25-30), mild (18-24), moderate (10-17), and severe (0-9) impairment. We used time-dependent Cox model to evaluate the relationship between time-varying cognition and mortality.ResultsThe relationship between cognition and mortality showed a dose-response pattern among the overall population. Compared to those with no impairment, participants with moderate (HR = 1.41, 95% CI 1.28-1.56) and severe (HR = 1.77, 95% CI 1.59-1.96) cognitive impairment showed increased mortality risk. Impairment in the subdomain of orientation was independently associated with increased mortality risk (HR = 1.20, 95% CI 1.05-1.36) among participants without overall cognitive impairment. Urban and rural residents had similar mortality risk.ConclusionsA consistent dose-response pattern existed between cognitive impairment and all-cause mortality. Orientation was associated with mortality in the population without cognitive impairment. Similar mortality regardless of residence areas indicated scarce health care and treatment for cognitive impairment in China from 1998 to 2014.
| S-EPMC8553308 | biostudies-literature
Project description:Vaccines against SARS-CoV-2 with good efficacy are now available worldwide. However, gained immunity diminishes over time. Here, we investigate the course of both humoral and cell-mediated immunity in response to three doses of the Pfizer mRNA BNT162b2 SARS-CoV-2 vaccine in healthcare workers in Japan. SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies (total Ig, IgG), neutralizing antibodies (NAb), and ELISpot were measured in serum and whole blood samples collected after each vaccine dose. ELISpot numbers were higher than the cutoff values in most participants at all times. It was suggested that the difference in behavior between humoral immunity and cell-mediated immunity with age is complementary. Anti-RBD total Ig, IgG, and NAb indicated a high correlation at each time point after vaccine doses. Total Ig was retained long-term after the second dose and increased significantly faster by the booster dose than IgG. Nab levels of all subjects were ≤20% six months after the second dose, and the correlation coefficient was greatly reduced. These are due to the avidity of each antibody and differences among commercial kits, which may affect the evaluation of immunokinetics in previous COVID-19 studies. Therefore, it is necessary to harmonize reagents categorized by the same characteristics.
| S-EPMC9323262 | biostudies-literature
Project description:In this single-center observational study with 1,206 participants, we prospectively evaluated SARS-CoV-2-antibodies (anti-S RBD) and vaccine-related adverse drug reactions (ADR) after basic and booster immunization with BNT162b2- and ChAdOx1-S-vaccines in four vaccination protocols: Homologous BNT162b2-schedule with second vaccination at either three or six weeks, homologous ChAdOx1-S-vaccination or heterologous ChAdOx1-S/BNT162b2-schedule, each at 12 weeks. All participants received a BNT162b2 booster. Blood samples for anti-S RBD analysis were obtained multiple times over a period of four weeks to six months after basic vaccination, immediately before, and up to three months after booster vaccination. After basic vaccination, the homologous ChAdOx1-S-group showed the lowest anti-S RBD levels over six months, while the heterologous BNT162b2-ChAdOx1-S-group demonstrated the highest anti-S levels, but failed to reach level of significance compared with the homologous BNT162b2-groups. Antibody levels were higher after an extended vaccination interval with BNT162b2. A BNT162b2 booster increased anti-S-levels 11- to 91-fold in all groups, with the homologous ChAdOx1-S-cohort demonstrated the highest increase in antibody levels. No severe or serious ADR were observed. The findings suggest that a heterologous vaccination schedule or prolonged vaccination interval induces robust humoral immunogenicity with good tolerability. Extending the time to boost-immunization is key to both improving antibody induction and reducing ADR rate.
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Project description:COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania. A total of 1048 randomly selected adults who received COVID-19 vaccines at different time points were enrolled and humoral immune responses (IR) were tested at baseline and three months later (960, 91.6%). The level of SARS-CoV-2 anti-spike/receptor binding domain (RBD) IgG, anti-nucleocapsid IgG, and IgM antibodies were determined using a commercially available chemiluminescent microparticle immunoassay. Descriptive data analysis was performed using STATA version 18 and R. At baseline, serum IgG against anti-spike/RBD was detected in 1010/1048 (96.4%) participants (95%CI: 94.9-97.5) and 98.3% (95%CI: 97.3-99) three months later. The IgG against the SARS-CoV-2 nucleocapsid proteins were detected in 40.8% and 45.3% of participants at baseline and follow-up, respectively. The proportion of seroconverters following vaccination and mean titers of anti-spike/RBD antibodies were significantly more among those who had past SARS-CoV-2 infection than in those with no evidence of past infection, (p < 0.001). Only 0.5% of those who had detectable anti-spike/RBD antibodies at baseline were negative after three months of follow-up and 1.5% had breakthrough infections. The majority of participants (99.5%) had detectable anti-spike/RBD antibodies beyond 6 months post-vaccination. The proportion of Tanzanians who mounted humoral IR following COVID-19 vaccination was very high. Seroconversions, as well as the mean titers and durability of humoral IR, were significantly enhanced by exposure to natural SARS-CoV-2 infection. In view of the limited availability of COVID-19 vaccines as well as challenges to completing subsequent doses, booster doses could only be suggested to high-risk groups.
| S-EPMC10819524 | biostudies-literature
Project description:BackgroundRoughly half of U.S. adults do not receive recommended booster vaccinations, but protective antibody levels are rarely measured in adults. Demographic factors, vaccination history, and responses to other vaccinations could help identify at-risk individuals. We sought to characterize rates of seroconversion and determine associations of humoral responses to multiple vaccinations in healthy adults.MethodsHumoral responses toward measles, mumps, tetanus toxoid, pertussis, hepatitis B surface antigen, and anthrax protective antigen were measured by ELISA in post-immunization samples from 1465 healthy U.S. military members. We examined the effects of demographic and clinical factors on immunization responses, as well as assessed correlations between vaccination responses.ResultsSubsets of boosted adults did not have seroprotective levels of antibodies toward measles (10.4%), mumps (9.4%), pertussis (4.7%), hepatitis B (8.6%) or protective antigen (14.4%) detected. Half-lives of antibody responses were generally long (>30 years). Measles and mumps antibody levels were correlated (r=0.31, p<0.001), but not associated with select demographic features or vaccination history. Measles and mumps antibody levels also correlated with tetanus antibody response (r=0.11, p<0.001).ConclusionsVaccination responses are predominantly robust and vaccine specific. However, a small but significant portion of the vaccinated adult population may not have quantitative seroprotective antibody to common vaccine-preventable infections.
| S-EPMC4323156 | biostudies-literature
Project description:BackgroundOlder adults are given high priority for coronavirus disease 2019 (COVID-19) vaccination; however, little is known about the safety of vaccines. This study was conducted to examine the safety of the COVID-19 vaccine for people who were ≥ 75 years of age, specifically those who first took two doses of the vaccine at the COVID-19 central vaccination center in South Korea.MethodsSafety monitoring after the BNT162b2 vaccine was conducted in three ways for older adults who received the first dose of the vaccine at our center between April 5 and April 23, 2021. For immediate adverse reactions, every person who was vaccinated was observed for 15-30 minutes after injection at the center. For active surveillance, a telephone interview was conducted for stratified randomly sampled people after 7 days of each vaccination to enquire regarding types of adverse reactions they experienced, and its severity and duration. For passive surveillance, reported adverse event data were collected from the COVID-19 vaccine adverse event following immunization (AEFI) surveillance system-run by the Korea Disease Control and Prevention Agency (KDCA). The data were then reviewed.ResultsIn total, 2,123 older adults received at least one vaccine dose during the study period. The frequency of acute adverse reactions that developed during the observed 15-30 minutes after injection was 8.5 cases per 1,000 doses. None of the reactions was assessed as acute allergic reactions to the vaccine and no cases required special treatment or drug administration. Overall, 638 people were followed up at least once by telephone interview 7 days post vaccination. The overall response rate was 82.3%. The rates of local reactions were 50.3% after the first dose and 45.2% after the second dose, and the rates of systemic reactions were 15.2% and 26.0%, respectively. During the study period, 23 medically attended adverse events (5.4 cases per 1,000 administered doses) were reported to the KDCA AEFI surveillance system. The most common symptoms of medically attended cases were nonspecific general weakness (26%) and dizziness (26%), followed by muscle pain (22%), headache (13%), fever (13%), and skin rash or urticaria (13%). Among them, there were five serious adverse events reported, which required hospitalization, including one death. However, most of them were not related to the vaccines.ConclusionBNT162b2 vaccination was tolerable among adults who were ≥ 75 years of age.
| S-EPMC8608922 | biostudies-literature