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BackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses. MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations. FindingsOur findings show a robust immune response to the Spike proteins RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose. InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine. FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms "SARS-CoV-2", "COVID-19", "vaccine response", "mRNA vaccine", up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects. Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose. Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.
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BackgroundHigh number of SARS-CoV-2 antibody tests are available in different formats, detect different types of antibodies, and use different target proteins. Sensitivity of these tests varies and could be also related to clinical symptoms and testing time. MethodsSerum samples from 97 COVID-19 patients and 100 controls were tested with 9 antibody tests (SNIBE, Epitope, Euroimmun, Roche, Abbott, DiaSorin, Biosensor, LIPS N, and LIPS S-RBD). The results were analyzed in context of clinical data. FindingsPositivity rate was of tests was following: N-LIPS test (91.8% cases), Epitope (85.6%), Abbott and in-house LIPS S-RBD (both 84.5%), Roche (83.5%), Euroimmun (82.5%), DiaSorin (81.4%), SNIBE (70.1%), and Biosensor (64.9%). Agreement between tests varied (71-95%). Correlation between patient symptoms score and antibody value was test-dependent: varied from strongest in LIPS N ({rho}=0.41; p<0.001) to nonsignificant (LIPS S-RBD). Testing time from symptoms influenced sensitivity in some tests more than anothers. InterpretationSensitivity of tests varied highly and combination of different tests may improve it. Relation of results to symptoms and testing time was test-dependent. Thus, some antibody tests seems to be more sensitive to detect antibodies early and in asymptomatic patients than others. FundingStudy was funded by SYNLAB Estonia and Estonian Research Council grant PRG377. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSHigh variation in COVID-19 antibody tests sensitivity has been described. Relation between antibody response and clinical cause has been found in some studies but not in others. Its known that antibody response is time dependent, however seroconversion medians varied in different studies. Added value of this studyWe confirmed that SARS-CoV-2 antibody response depends on clinical symptoms and time of testing, but we also found that this relation is dependent on test setup and viral antigens used in the tests. This may explain contradictory results of previous studies. Implications of all the available evidenceOur study has practical implications showing that not all antibody tests work uniformly well in symptomatic and asymptomatic cases and in different time periods from disease onset. This should be taken into consideration in clinical practice for diagnosing COVID-19 and in epidemiological studies evaluating the seroprevalence especially in asymptomatic population.
