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      SARS-CoV-2 Antibody response after BNT162b2 mRNA vaccine in healthcare workers: nine-month of follow-up

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          Abstract

          We collected sequential serum samples (0, 4, 12 weeks, 9 months) for the determination of S-RDB IgG levels from 103 vaccinated healthy subjects (age 45±13 years; 60 women), in order to evaluate neutralizing antibody response against SARS-CoV-2 in healthy healthcare workers (HCWs) after the administration of two doses of BNT162b2 SARS-CoV-2 mRNA vaccine. Every subject received two doses of mRNA vaccine BNT162b2 (Pfizer-BioNTech), 21 days apart (January-February 2021). Furthermore, antibody titer of 14 subjects who were hospitalized for symptomatic COVID-19 was evaluated. Antibody response was (median, interquartile range) 35 U/mL (10-104) at baseline, 1960 (1241-3221) at 4 weeks, 791 (388-1179) at 12 weeks and 524 (273-931) at 6 months. Antibody response was inversely correlated with age at all timepoints (p<0.001) while gender and Body Mass Index had no significant effect. At multivariate analysis, post-baseline values were significantly higher than baseline (p<0.001) with a reduction at 12 weeks and 9 months (p<0.001). Antibody response of hospitalized subjects who did not receive vaccination, symptomatic for COVID 19 infection, was 103 (25-557) U/mL, significantly higher than baseline (p=0.007) of study population but lower than all post-baseline determinations (p<0.001). Younger subjects showed a stronger response and a lower decrease of antibody titers compared to the classes of older subjects. SARS-CoV2 infection was excluded by performing 1017 nasopharyngeal RT-PCR swabs on the study cohort. The second dose of mRNA vaccine resulted in an antibody response effective in preventing infection in a population of healthcare professionals. The antibody level was stable through week 12, showing a reduction in the following six months.

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          Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

          Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. Methods In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. Results A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. Conclusions The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
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            A serological assay to detect SARS-CoV-2 seroconversion in humans

            Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.
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              Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults

              Abstract Background Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age. Methods We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. Results Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells. Conclusions In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.)
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                Author and article information

                Journal
                Vaccine X
                Vaccine X
                Vaccine: X
                Published by Elsevier Ltd.
                2590-1362
                6 June 2022
                6 June 2022
                : 100175
                Affiliations
                Regional General Hospital “F. Miulli”, Acquaviva delle Fonti, Bari, Italy
                Author notes
                [* ]Corresponding author at: Internal Medicine Department Regional General Hospital “F. Miulli” Acquaviva delle Fonti, Bari, Italy.
                Article
                S2590-1362(22)00035-3 100175
                10.1016/j.jvacx.2022.100175
                9170276
                35692461
                ec8f357f-b7e2-4dda-bebf-72b692b878e0
                © 2022 Published by Elsevier Ltd.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 23 November 2021
                : 10 May 2022
                : 2 June 2022
                Categories
                Article

                covid-19,antibody responses,vaccine
                covid-19, antibody responses, vaccine

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