No correlation of neutralizing antibody titers against the Omicron variant after a booster dose of COVID-19 vaccines with subsequent breakthrough Omicron infections among healthcare workers.
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ABSTRACT:
SUBMITTER: Lee J
PROVIDER: S-EPMC9548087 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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No correlation of neutralizing antibody titers against the Omicron variant after a booster dose of COVID-19 vaccines with subsequent breakthrough Omicron infections among healthcare workers.
Lee Jeongjae J Park Soonju S Kim Ji Yeun JY Lim So Yun SY Chang Euijin E Bae Seongman S Jung Jiwon J Kim Min Jae MJ Chong Yong Pil YP Lee Sang-Oh SO Choi Sang-Ho SH Kim Yang Soo YS Lee Nakyung N Shum David D Kim Seungtaek S Jee Youngmee Y Kim Sung-Han SH
The Journal of infection 20221009 6
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Project description:BackgroundThe spread of the vaccine-resistant Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens unvaccinated and fully vaccinated individuals, and accelerated booster vaccination campaigns are underway to mitigate the ongoing wave of Omicron cases. The immunity provided by standard vaccine regimens, boosted regimens, and immune responses elicited by vaccination plus natural infection remain incompletely understood. The magnitude, quality, and durability of serological responses, and the likelihood of protection against future SARS-CoV-2 variants following these modes of exposure, are poorly characterized but are critical to the future trajectory of the coronavirus disease 2019 (COVID-19) pandemic.MethodsNinety-nine individuals were semi-randomly selected from a larger vaccination cohort following vaccination and, in some cases, breakthrough infection. We analyzed spike receptor-binding domain-specific immunoglobulin G (IgG), IgA, and IgM by enzyme-linked immunosorbent assay, neutralizing antibody titers against live SARS-CoV-2 variants, and antibody-dependent cell-mediated phagocytosis.FindingsIn 99 vaccinated adults, compared with responses after two doses of an mRNA regimen, the immune responses 3 months after a third vaccine dose and 1 month after breakthrough infection due to prior variants show dramatic increases in magnitude, potency, and breadth, including increased antibody-dependent cellular phagocytosis and robust neutralization of the currently circulating Omicron BA.2 variant.ConclusionsBoosters and natural infection substantially boost immune responses. As the number of Omicron sub-variant cases rise and as global vaccination and booster campaigns continue, an increasing proportion of the world's population will acquire potent immune responses that may be protective against future SARS-CoV-2 variants.FundingThis work was funded by the M. J. Murdock Charitable Trust, the OHSU Foundation, the NIH (T32HL083808), and OHSU Innovative IDEA.
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Project description:BackgroundLongitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron.MethodsParticipants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups.ResultsBreakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients.ConclusionsSymptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.
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Project description:It remains unknown whether the Indonesian healthcare workers (HCWs) who had received two doses of CoronaVac vaccine and one dose of mRNA-1273 booster could be protected during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave. In total, 125 infection-naïve and 10 previously infected HCWs were recruited. The mRNA-1273 booster substantially increased titer of anti-SARS-CoV-2 spike protein receptor-binding domain antibodies. However, the monitoring revealed that 34 out of 125 infection-naïve (27.2%) and 3 out of 10 previously infected HCWs (30.0%) were infected during the Omicron wave. All infected HCWs were either asymptomatic or having mild coronavirus disease 2019 (COVID-19) and subsequently fully recovered, supporting the heterologous prime-boost strategy against COVID-19.
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Project description:BackgroundDefining the protective thresholds against the severe-acute-respiratory-syndrome-related corona virus-2 pandemic is a crucial challenge. To reduce the risks of severe disease, hospitalization, and death, various COVID-19 vaccines have been rapidly developed.Aim of the workThis study aimed to assess the impact of three common COVID-19 vaccine types; two mRNA COVID-19 vaccines: (Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273), one adenoviral vector vaccine: Oxford/AstraZeneca's ChAdOx1, and one inactivated vaccine (Sinovac Biotech/China's Sinovac) on the level of neutralizing antibodies, considering factors such as vaccine type, demographic characteristics, and hybrid immunity. We conducted a direct comparative analysis involving 300 healthcare workers, both with and without prior SARS-CoV-2 infection (B.1, C.36.3, and AY.32 (Delta) variants). Neutralizing antibodies levels were measured at baseline (before vaccination), before the second dose, and six months after the second dose.ResultsThe results showed a significant increase in neutralizing antibodies levels after complete vaccination with all vaccine types. Among healthcare workers, those vaccinated with mRNA vaccines (Moderna or Pfizer) exhibited the highest neutralizing antibodies titers, followed by AstraZeneca, and finally Sinovac with the lowest titer. On studying the effect of previous COVID-19 infection after vaccination, no significant difference in neutralizing antibodies levels was observed between healthcare workers vaccinated with mRNA or AstraZeneca vaccines, both with prior COVID-19 infection, following the first and six months after the second dose.ConclusionThese findings suggest that individuals with prior COVID-19 may only require a single dose of mRNA or AstraZeneca vaccines to achieve a similar level of immunization as those without prior COVID-19 who completed the vaccination program.HighlightsThere is a significant increase in neutralizing antibodies levels after complete vaccination against COVID-19 Vaccination with mRNA vaccines exhibits the highest neutralizing antibodies titers. Vaccination with Sinovac exhibits the lowest neutralizing antibodies titers.
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Project description:The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding antibody responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function, and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in convalescent donors who had been hospitalized with severe illness, and are cross-reactive against diverse SARS-CoV-2 variants, including the neutralization-resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.
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Project description:Vaccination offers protection against severe COVID-19 caused by SARS-CoV-2 omicron but is less effective against infection. Characteristics such as serum antibody titer correlation to protection, viral abundance and clearance of omicron infection in vaccinated individuals are scarce. We present a 4-week twice-weekly SARS-CoV-2 qPCR screening in 368 triple vaccinated healthcare workers. Spike-specific IgG levels, neutralization titers and mucosal spike-specific IgA-levels were determined at study start and qPCR-positive participants were sampled repeatedly for two weeks. 81 (cumulative incidence 22%) BA.1, BA.1.1 and BA.2 infections were detected. High serum antibody titers are shown to be protective against infection (p < 0.01), linked to reduced viral load (p < 0.01) and time to viral clearance (p < 0.05). Pre-omicron SARS-CoV-2 infection is independently associated to increased protection against omicron, largely mediated by mucosal spike specific IgA responses (nested models lr test p = 0.02 and 0.008). Only 10% of infected participants remain asymptomatic through the course of their infection. We demonstrate that high levels of vaccine-induced spike-specific WT antibodies are linked to increased protection against infection and to reduced viral load if infected, and suggest that the additional protection offered by pre-omicron SARS-CoV-2 infection largely is mediated by mucosal spike-specific IgA.
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Project description:BackgroundVaccinations against the SARS-CoV-2 are still crucial in combating the ongoing pandemic that has caused more than 700 million infections and claimed almost 7 million lives in the past four years. Omicron (B.1.1.529) variants have incurred mutations that challenge the protection against infection and severe disease by the current vaccines, potentially compromising vaccination efforts.MethodsWe analyzed serum samples taken up to 9 months post third dose from 432 healthcare workers. Enzyme-linked immunosorbent assays (ELISA) and microneutralization tests (MNT) were used to assess the prevalence of vaccine-induced neutralizing antibodies against various SARS-CoV-2 Omicron variants.ResultsIn this serological analysis we show that SARS-CoV-2 vaccine combinations of BNT162b2, mRNA-1273, and ChAdOx1 mount SARS-CoV-2 binding and neutralizing antibodies with similar kinetics, but with differing neutralization capabilities. The most recent Omicron variants, BQ.1.1 and XBB.1.5, show a significant increase in the ability to escape vaccine and infection-induced antibody responses. Breakthrough infections in thrice vaccinated adults were seen in over 50% of the vaccinees, resulting in a stronger antibody response than without infection.ConclusionsDifferent three-dose vaccine combinations seem to induce considerable levels of neutralizing antibodies against most SARS-CoV-2 variants. However, the ability of the newer variants BQ1.1 and XBB 1.5 to escape vaccine-induced neutralizing antibody responses underlines the importance of updating vaccines as new variants emerge.
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Project description:The emergence of new variants and diverse vaccination regimens have raised uncertainty about vaccine effectiveness against SARS-CoV-2. This study aims to investigate the impact of Omicron primo-/reinfection and primary vaccination schedules on the immunogenicity of an mRNA-based booster dose over a six-month period. We conducted a prospective cohort study to assess the durability and level of antibodies of 678 healthcare workers fully vaccinated against COVID-19. They were categorized based on their primary vaccination regimen. Blood samples were collected before the booster dose and 1 and 6 months after. Significant Anti-S-RBD differences were found between previously infected and naïve volunteers (p = 0.01). Considering the initial vaccine schedules, mRNA-based vaccines displayed significant higher antibody production and longer persistence among both infected and naïve participants. After the booster dose, participants primoinfected with the Omicron variant exhibited higher antibody concentrations than those who experienced reinfection, even after 6 months of follow-up (22,545 and 9460 U/mL, respectively). Moreover, these groups showed the most pronounced disparity in antibody titers ratios between infected and uninfected individuals. Overall, the booster dose failed to enhance humoral response in individuals reinfected with the Omicron variant after receiving it. Hybrid immunity and mRNA-based vaccine initial schedules showed higher levels and longer persistence of antibodies.
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