ABSTRACT
This work evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.4 and BA.5) in healthcare workers who had breakthrough BA.1 infection. Omicron breakthrough infection in individuals vaccinated three or four times before infection resulted in increased neutralising antibodies against the WT virus. The fourth vaccine dose did not further improve the neutralising efficiency over the third dose against all Omicron variants, especially BA.4 and BA.5. An Omicron-specific vaccine may be indicated.
Subject(s)
COVID-19 , Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Israel/epidemiology , SARS-CoV-2/genetics , Vaccination/methodsABSTRACT
As the effectiveness of a two-dose messenger RNA (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine regimen decreases with time, a third dose has been recommended. Here, we assessed immunogenicity, vaccine effectiveness and safety of the third BNT162b2 vaccine dose in a prospective cohort study of 12,413 healthcare workers (HCWs). Anti-RBD immunoglobulin G (IgG) levels were increased 1.7-fold after a third dose compared with following the second dose. Increased avidity from 61.1% (95% confidence interval (CI), 56.1-66.7) to 96.3% (95% CI, 94.2-98.5) resulted in a 6.1-fold increase in neutralization titer. Peri-infection humoral markers of 13 third-dose Delta variant of concern (VOC) breakthrough cases were lower compared with 52 matched controls. Vaccine effectiveness of the third dose relative to two doses was 85.6% (95% CI, 79.2-90.1). No serious adverse effects were reported. These results suggest that the third dose is superior to the second dose in both quantity and quality of IgG antibodies and safely boosts protection from infection.
Subject(s)
COVID-19 , Vaccines , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Prospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose. METHODS: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys. RESULTS: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events. CONCLUSIONS: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age.
Subject(s)
BNT162 Vaccine/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Age Factors , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/adverse effects , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Female , Health Personnel , Humans , Immunoglobulin G/blood , Male , Middle Aged , RNA, Messenger , SARS-CoV-2ABSTRACT
IntroductionThe COVID-19 pandemic has put healthcare workers (HCW) at significant risk. Presence of antibodies can confirm prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.AimThis study investigates the prevalence of IgA and IgG antibodies against SARS-CoV-2 in HCW.MethodsPerformance of IgA and IgG antibody ELISA assays were initially evaluated in positive and negative SARS-CoV-2 serum samples. IgA and IgG antibodies against SARS-CoV-2 were measured in 428 asymptomatic HCW. We assessed the risk of two groups: HCW with high exposure risk outside work (HROW) residing in areas where COVID-19 was endemic (n = 162) and HCW with high exposure risk at work (HRAW) in a COVID-19 intensive care unit (ICU) (n = 97).ResultsSensitivities of 80% and 81.2% and specificities of 97.2% and 98% were observed for IgA and IgG antibodies, respectively. Of the 428 HCW, three were positive for IgG and 27 for IgA. Only 3/27 (11%) IgA-positive HCW had IgG antibodies compared with 50/62 (81%) in a group of previous SARS-CoV-2-PCR-positive individuals. Consecutive samples from IgA-positive HCW demonstrated IgA persistence 18-83 days in 12/20 samples and IgG seroconversion in 1/20 samples. IgA antibodies were present in 8.6% of HROW and 2% of HRAW.ConclusionsSARS-CoV-2 exposure may lead to asymptomatic transient IgA response without IgG seroconversion. The significance of these findings needs further study. Out of work exposure is a possible risk of SARS-CoV-2 infection in HCW and infection in HCW can be controlled if adequate protective equipment is implemented.