Variant-specific antibody correlates of protection against SARS-CoV-2 Omicron symptomatic and overall infections DOI Creative Commons
José Víctor Zambrana, Ian A. Mellis,

Abigail Shotwell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Vaccination and prior infection elicit neutralizing antibodies targeting SARS-CoV-2, yet the quantitative relationship between serum risk against viral variants remains uncertain, particularly in underrepresented regions. We investigated protective correlation of pre-exposure antibody levels, employing a panel SARS-CoV-2 pseudoviruses (Omicron BA.1, Omicron BA.2, ancestral D614G), Spike-binding with symptomatic BA.1 or BA.2 infections overall infection, 345 household contacts from cohort study. A four-fold increase homotypic-neutralizing (e.g., BA.1-neutralizing vs. exposure) titers was correlated protection (BA.1 protection: 28% [95%CI 12-42%]; 43% [20-62%]), ancestral-neutralizing were also either variant, but only at higher average levels than homotypic. Mediation analyses revealed that homotypic D614G-neutralizing mediated both vaccination. These findings underscore importance monitoring variant-specific responses highlight circulating strains may be more predictive infection. Nevertheless, ancestral-strain-neutralizing remain relevant as correlate protection. Our study emphasizes need for continued efforts to assess correlates acknowledge funding U.S. N.I.H., Open Philanthropy Project, Bill Melinda Gates Foundation. Based on searches Google Scholar PubMed, not restricted English-language articles, using search terms including "correlates protection," "SARS-CoV-2," "COVID-19," "BA.1," "BA.2," "neutralizing antibodies," "immune response," "thresholds protection" we identified multiple studies, primarily based randomized clinical trials prospective designs, which have shown SARS-CoV-2-neutralizing are informative after vaccination limited 2020 later, included several high-quality RCTs well consideration published meta-analyses. Often used spike-binding -neutralizing peak baseline months before waves, specific exposures participants remained unknown. Most evidence related focused strain even when challenged later variants, although small number groups directed contemporaneous strains, such BA.1. Furthermore, most studies vaccines widely available North America Europe; few globally COVID-19 vaccines, Soberana Sputnik. Relatedly, Central region has had no known protection, best our knowledge, despite unique vaccine exposure histories its residents widespread became available. In this study, household-based design an embedded transmission collected members just they exposed co-resident who developed COVID-19. This enabled analysis time exposure, relatively homogeneously across cohort. conducted Managua, Nicaragua, during presenting first America, received some global vaccines. pseudovirus neutralization assays allowing parallel anti-Omicron titers. Overall, results combination evidence, continue point Titers case), lower those strain, titer still Lastly, any history studied analysis, appear mediate effects

Language: Английский

SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19 DOI
Caroline Hirsch,

Yun Soo Park,

Vanessa Piechotta

et al.

Cochrane library, Journal Year: 2022, Volume and Issue: 2022(6)

Published: June 17, 2022

Language: Английский

Citations

40
Antibody correlates of protection from SARS-CoV-2 reinfection prior to vaccination: A nested case-control within the SIREN study DOI Creative Commons
Ana Atti, Ferdinando Insalata, Edward J Carr

et al.

Journal of Infection, Journal Year: 2022, Volume and Issue: 85(5), P. 545 - 556

Published: Sept. 9, 2022

ObjectivesTo investigate serological differences between SARS-CoV-2 reinfection cases and contemporary controls, to identify antibody correlates of protection against reinfection.MethodsWe performed a case-control study, comparing with singly infected individuals pre-vaccination, matched by gender, age, region timing first infection. Serum samples were tested for anti-SARS-CoV-2 spike (anti-S), nucleocapsid (anti-N), live virus microneutralisation (LV-N) pseudovirus (PV-N). Results analysed using fixed effect linear regression fitted into conditional logistic models.ResultsWe identified 23 92 controls. First infections occurred before November 2020; reinfections February 2021, pre-vaccination. Anti-S levels, LV-N PV-N titres significantly lower among cases; no difference was found anti-N levels. Increasing anti-S levels associated reduced risk (OR 0·63, CI 0·47-0·85), but association 0·88, 0·73-1·05). Titres >40 correlated Wuhan 0·02, 0·001–0·31) Alpha 0·07, 0·009–0·62). For PV-N, >100 0·14, 0·03–0·64) (0·06, 0·008–0·40).ConclusionsBefore vaccination, directly titres, not Detectable sufficient protection, whilst required protective effect.Trial registration numberISRCTN11041050

Language: Английский

Citations

39
Effects of COVID-19 vaccination and previous infection on Omicron SARS-CoV-2 infection and relation with serology DOI Creative Commons
Brechje de Gier, Anne J. Huiberts, Christina E. Hoeve

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 9, 2023

Abstract An increasing proportion of the population has acquired immunity through COVID-19 vaccination and previous SARS-CoV-2 infection, i.e., hybrid immunity, possibly affecting risk new infection. We aim to estimate protective effect infections vaccinations on Omicron using data from 43,257 adult participants in a prospective community-based cohort study Netherlands, collected between 10 January 2022 1 September 2022. Our results show that, for with 2, 3 or 4 prior immunizing events (vaccination infection), is more against infection than vaccine-induced up at least 30 weeks after last event. Differences are partly explained by differences anti-Spike RBD (S) antibody concentration, which associated dose-response manner. Among one pre-Omicron we do not observe relevant difference sequence vaccination(s) Additional increase protection but above level first

Language: Английский

Citations

36
Correlates of protection for booster doses of the SARS-CoV-2 vaccine BNT162b2 DOI Creative Commons
Tomer Hertz, Shlomia Levy, Daniel Ostrovsky

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 29, 2023

Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates (COP) in a multicenter prospective study following 607 healthy individuals who received three doses Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 fourth dose 365 did not. Within 90 days enrollment, 239 contracted 45% 3-dose group 30% four-dose group. The elicited rise antibody binding neutralizing titers VOCs reducing risk symptomatic infection by 37% [95%CI, 15%-54%]. However, individuals, characterized low baseline antibodies, remained susceptible despite significantly increased upon boosting. A combination reduced IgG levels RBD mutants VOC-recognizing IgA antibodies represented strongest COP both (HR = 6.34, p 0.008) 8.14, 0.018). validated our findings an independent second cohort. In summary may most from future infections.

Language: Английский

Citations

27
Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies DOI Creative Commons
Nathan J. Cheetham, Milla Kibble, Andrew Wong

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Jan. 24, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher anti-Spike antibodies are known associated with increased protection against However, variation in factors for lower each round vaccination have not been explored across a wide range socio-demographic, health within population-based cohorts.

Language: Английский

Citations

25
Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70 DOI
Byron Brook, Valérie Duval, Soumik Barman

et al.

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(757)

Published: July 24, 2024

Messenger RNA (mRNA) vaccines were pivotal in reducing severe acute respiratory syndrome 2 (SARS-CoV-2) infection burden, yet they have not demonstrated robust durability, especially older adults. Here, we describe a molecular adjuvant comprising lipid nanoparticle (LNP)–encapsulated mRNA encoding interleukin-12p70 (IL-12p70). The bioactive was engineered with multiorgan protection (MOP) sequence to restrict transcript expression the intramuscular injection site. Admixing IL-12–MOP (CTX-1796) BNT162b2 SARS-CoV-2 vaccine increased spike protein–specific immune responses mice. Specifically, benefits of adjuvantation included amplified humoral and cellular immunity durability for 1 year after vaccination An additional benefit restoration aged mice amounts comparable those achieved young adult animals, alongside amplification single immunization. Associated enhanced dendritic cell germinal center observed. Together, these data demonstrate that an LNP-encapsulated mRNA-encoded can amplify immunogenicity independent age, demonstrating translational potential vulnerable populations.

Language: Английский

Citations

13
Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection DOI Creative Commons
Beatriz Escudero-Pérez, Philip Lawrence, Javier Castillo‐Olivares

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: April 17, 2023

Correlates of protection (CoP) are biological parameters that predict a certain level against an infectious disease. Well-established correlates facilitate the development and licensing vaccines by assessing protective efficacy without need to expose clinical trial participants agent which vaccine aims protect. Despite fact viruses have many features in common, can vary considerably amongst same virus family even depending on infection phase is under consideration. Moreover, complex interplay between various immune cell populations interact during high degree genetic variation pathogens, renders identification difficult. Some emerging re-emerging consequence for public health such as SARS-CoV-2, Nipah (NiV) Ebola (EBOV) especially challenging with regards CoP since these pathogens been shown dysregulate response infection. Whereas, neutralising antibodies polyfunctional T-cell responses correlate levels EBOV NiV, other effector mechanisms immunity play important roles shaping turn might serve alternative protection. This review describes different components adaptive innate system activated NiV infections may contribute clearance. Overall, we highlight signatures associated humans could be used CoP.

Language: Английский

Citations

17
Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection DOI Creative Commons
Javier Perez‐Saez, María-Eugenia Zaballa, Julien Lamour

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 26, 2023

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection infection with pre-Omicron lineages. This has been challenged by the emergence immune-evasive variants, notably Omicron sublineages, in an evolving immune landscape high cumulative incidence and vaccination coverage. turn limits use widely available commercial high-throughput methods quantify binding antibodies as a tool monitor at population-level. Here we show that anti-Spike RBD levels, quantified immunoassay used this study, are indirect correlate BA.1/BA.2 for individuals previously infected SARS-CoV-2. Leveraging repeated serological measurements between April 2020 December 2021 on 1083 participants population-based cohort Geneva, Switzerland, using kinetic modeling, found up three-fold reduction hazard having documented positive during wave anti-S above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, did not detect among uninfected participants. These results provide reassuring insights into continued interpretation independent marker both individual population levels.

Language: Английский

Citations

16
Emerging heterologous mRNA-based booster strategies within the COVID-19 vaccine landscape DOI Creative Commons
Rituparna Das,

Randall N. Hyer,

Paul R. Burton

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2023, Volume and Issue: 19(1)

Published: Jan. 2, 2023

Messenger RNA (mRNA)-based vaccine platforms used for the development of mRNA-1273 and BNT162b2 have provided a robust adaptable approach to offer protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, as variants concern (VoCs), such omicron associated sub-variants, emerge, boosting strategies must also adapt keep pace with changing landscape. Heterologous vaccination regimens involving administration booster vaccines different than primary series practical, effective, safe continue reduce global burden disease 2019 (COVID-19). To understand immunogenicity, effectiveness, safety heterologous mRNA-based strategies, relevant clinical real-world observational studies were identified summarized. Overall, that are currently available those in will play an important role protecting individuals from COVID-19 caused by emerging VoCs.

Language: Английский

Citations

14
Anti-nucleocapsid antibody levels following initial and repeat SARS-CoV-2 infections in a cohort of long-term care facility residents in England (VIVALDI) DOI Creative Commons
Oliver Stirrup, Gokhan Tut, Maria Krutikov

et al.

Wellcome Open Research, Journal Year: 2024, Volume and Issue: 9, P. 45 - 45

Published: Feb. 19, 2024

We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels anti-spike antibodies are comparable to general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on humoral response other SARS-CoV-2 proteins associated with natural infection scarce this vulnerable population.

Language: Английский

Citations

6