RESUMO
Secretory immunoglobulin A (IgA) plays a crucial role in the mucosal immunity for preventing the invasion of the exogenous antigens, however, little has been understood about the neutralizing activity of serum IgA. Here, to examine the role of IgA antibodies against COVID-19 illnesses, we determined the neutralizing activity of serum/plasma IgG and IgA purified from previously SARS-CoV-2-infected and COVID-19 mRNA-vaccine-receiving individuals. We found that serum/plasma IgA possesses substantial but rather modest neutralizing activity against SARS-CoV-2 compared to IgG with no significant correlation with the disease severity. Neutralizing IgA and IgG antibodies achieved the greatest activity at approximately 25 and 35 days after symptom onset, respectively. However, neutralizing IgA activity quickly diminished and went down below the detection limit approximately 70 days after onset, while substantial IgG activity was observed till 200 days after onset. The total neutralizing activity in sera/plasmas of those with COVID-19 largely correlated with that in purified-IgG and purified-IgA and levels of anti-SARS-CoV-2-S1-binding IgG and anti-SARS-CoV-2-S1-binding IgA. In individuals who were previously infected with SARS-CoV-2 but had no detectable neutralizing IgA activity, a single dose of BNT162b2 or mRNA-1273 elicited potent serum/plasma neutralizing IgA activity but the second dose did not further strengthen the neutralization antibody response. The present data show that the systemic immune stimulation with natural infection and COVID-19 mRNA-vaccines elicit both SARS-CoV-2-specific neutralizing IgG and IgA response in serum, but the IgA response is modest and diminishes faster compared to IgG response.
Assuntos
COVID-19 , Síndrome Respiratória Aguda GraveRESUMO
In the present prospective study, 225 individuals in Kumamoto General Hospital, Japan, who received two-doses of BNT162b2 vaccine were enrolled/followed up over 150 days. Neutralizing activity (NT50) of sera on day-60 post-1st -dose against wild-type (SARS-CoV-2Wuhan)(n = 211) and 9 variants (VOCs; Alpha/Beta/Gamma/Delta, and VUM; Kappa)(n = 45) were examined. Also, antiviral activity (EC50) of IgG obtained from day-60 sera against SARS-CoV-2Wuhan and 9 variants were evaluated (n = 45). Finally, time-dependent alterations of IgG-activity (n = 25) against SARS-CoV-2Wuhan/variants were examined. Day-60 sera showed reduced NT50 by more than 50% against all variants, and greatest reduction was seen with Beta. IgG of high-responders (IgGhighs) and moderate-responders (IgGmoderates) showed similar fold-changes in EC50 against each variant compared to SARS-CoV-2Wuhan. However, absolute EC50 of IgGhighs were 2 ~ 3-folds greater than those of IgGmoderates against all SARS-CoV-2s. Evaluation of EC50 of IgG obtained at different time-points (day-28 to -150) revealed time-dependent reduction of IgG-activity against various VOCs/VUM. However, against Delta, relatively long-lasting favorable EC50 (at least 150 days) of both IgG were observed. Our data strongly suggest that rapid expansion of vaccine administration in Japan was remarkably effective to repress SARS-CoV-2 pandemic with the spread of Delta, and give insights in better understanding of the antiviral-efficacy of SARS-CoV-2 vaccine and vaccine-elicited immune-response.
RESUMO
While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT 50 ; assessed using infectious virions) with various determinants were examined and the potency of serums against variants of concerns was determined. Significant rise in NT 50 s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT 50 s and ages, but no correlation seen between NT 50 s and adverse effects. NT 50 s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of NT 50 s was ~ 68 days and the estimated average time length till the total disappearance of neutralizing activity was ~ 198 days. While serums from elite-responders (NT 50 s > 1,500-fold: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some serums with low NT 50 s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.
RESUMO
Background: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified. Methods: In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined. Findings: Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation was seen between NT50s and AEs. NT50s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT50s>1,500-fold: the top 4% among all participants' NT50s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT50s failed to block the infectivity of a beta strain. Interpretation: BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed.
Assuntos
DorRESUMO
Background: While mRNA vaccines against SARS-CoV-2 have been exceedingly effective in preventing symptomatic viral infection, the features of immune response remain to be clarified.Methods: In the present prospective observational study, 225 healthy individuals in Kumamoto General Hospital, Japan, who received two BNT162b2 doses in February 2021, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions and live target cells) with SARS-CoV-2-S1-binding-IgG and -IgM levels, adverse effects (AEs), ages, and genders were examined. The average half-life of neutralizing activity and the average time length for the loss of detectable neutralizing activity were determined and the potency of serums against variants of concerns was also determined.Findings: Significant rise in NT50s was seen in serums on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation was seen between NT50s and AEs. NT50s and IgG levels on day 28 post-1st dose and pain scores following the 2nd shot were greater in women than in men. The average half-life of neutralizing activity in the vaccinees was approximately 67.8 days and the average time length for their serums to lose the detectable neutralizing activity was 198.3 days. While serums from elite-responders (NT50s >1,500-fold: the top 4% among all participants’ NT50s) potently to moderately blocked the infectivity of variants of concerns, some serums with moderate NT50s failed to block the infectivity of a beta strain.Interpretation: BNT162b2-elicited immune response has no significant association with AEs. BNT162b2-efficacy is likely diminished to under detection limit by 6-7 months post-1st shot. High-level neutralizing antibody-containing serums potently to moderately block the infection of SARS-CoV-2 variants; however, a few moderate-level neutralizing antibody-containing serums failed to do so. If BNT162b2-elicited immunity memory is short, an additional vaccine or other protective measures would be needed.Funding Information: This research was supported in part by a grant from the Japan Agency for Medical Research and Development to Maeda (grant number JP20fk0108260, 20fk0108502) and to Mitsuya (grant number 20fk0108502), and in part by a grant for MHLW Research on Emerging and Re-emerging Infectious Diseases and Immunization Program to Maeda (grant number JPMH20HA1006) from Ministry of Health, Labor and Welfare, and in part by a grant for COVID-19 to Mitsuya (grant number 19A3001) and Maeda (grant number 20A2003D) from the Intramural Research Program of National Center for Global Health and Medicine, and in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health (Mitsuya).Declaration of Interests: Matsushima, Noda, Sato, and Yoshida are employees of SysmexCorporation.Other authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.Ethics Approval Statement: The Ethics Committees from the Kumamoto General Hospital and NCGM approved this study (Kumamoto General Hospital No. 180, and NCGM-G-004176-00, respectively). Each participant provided a written informed consent, and this study abided by the Declaration of Helsinki principles.