The challenge of limited vaccine supplies: impact of prior infection on anti-spike IgG antibody trajectories after a single COVID-19 vaccination

AbstractGiven high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out, there is an urgent need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity at speed. We evaluate whether a single vaccination in previously infected individuals generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single dose of ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults who received at least one vaccination, 13,404 (13.3%) had serological and/or PCR evidence of prior infection. Prior infection significantly boosted antibody responses for all three vaccines, producing a higher peak level and longer half-life, and a response comparable to those without prior infection receiving two vaccinations. In those with prior infection, median time above the positivity threshold was estimated to last for >1 year after the first dose. Single-dose vaccination targeted to those previously infected may provide protection in populations with high rates of previous infection faced with limited vaccine supply, as an interim measure while vaccine campaigns are scaled up.

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SARS-CoV-2 anti-spike IgG antibody responses after second dose of ChAdOx1 or BNT162b2 in the UK general population

10.1101/2021.09.13.21263487 ◽

2021 ◽

Author(s):

Jia Wei ◽

Koen B. Pouwels ◽

Nicole Stoesser ◽

Philippa C. Matthews ◽

Ian Diamond ◽

...

Keyword(s):

General Population ◽

Booster Dose ◽

Peak Level ◽

Antibody Responses ◽

Short Term ◽

Igg Antibody ◽

The Uk ◽

Dosing Intervals ◽

Antibody Levels ◽

Prior Infection

We investigated anti-spike IgG antibody responses following second doses of ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines in the UK general population. In 186,527 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Antibody levels declined faster at older ages than younger ages with BNT162b2, but were similar across ages with ChAdOX1. With both vaccines, prior infection significantly increased antibody peak level and half-life. Protection was estimated to last for 0.5-1 year after ChAdOx1 and >1 year after BNT162b2, but could be reduced against emerging variants. Reducing the dosing interval to 8 weeks for both vaccines or further to 3 weeks for BNT162b2 may help increase short-term protection against the Delta variant. A third booster dose may be needed, prioritised to more vulnerable people.

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Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Gut ◽

10.1136/gutjnl-2021-324789 ◽

2021 ◽

pp. gutjnl-2021-324789

Author(s):

Nicholas A Kennedy ◽

Simeng Lin ◽

James R Goodhand ◽

Neil Chanchlani ◽

Benjamin Hamilton ◽

...

Keyword(s):

Single Dose ◽

Primary Outcome ◽

Geometric Mean ◽

Antibody Responses ◽

Antibody Assay ◽

Past Infection ◽

White Ethnicity ◽

Registration Number ◽

Inflammatory Bowel ◽

Prior Infection

ObjectiveDelayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.DesignAntibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3–10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.ResultsGeometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn’s disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.ConclusionInfliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.Trial registration numberISRCTN45176516.

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Impact of vaccination on SARS-CoV-2 cases in the community: a population-based study using the UK’s COVID-19 Infection Survey

10.1101/2021.04.22.21255913 ◽

2021 ◽

Author(s):

Emma Pritchard ◽

Philippa C. Matthews ◽

Nicole Stoesser ◽

David W. Eyre ◽

Owen Gethings ◽

...

Keyword(s):

Cohort Study ◽

Single Dose ◽

Population Based ◽

Rt Pcr ◽

Population Based Study ◽

Viral Shedding ◽

Asymptomatic Infections ◽

The Uk ◽

Prior Infection ◽

Nose And Throat

AbstractObjectivesTo assess the effectiveness of COVID-19 vaccination in preventing SARS-CoV-2 infection in the community.DesignProspective cohort study.SettingThe UK population-representative longitudinal COVID-19 Infection Survey.Participants373,402 participants aged ≥16 years contributing 1,610,562 RT-PCR results from nose and throat swabs between 1 December 2020 and 3 April 2021.Main outcome measuresNew RT-PCR-positive episodes for SARS-CoV-2 overall, by self-reported symptoms, by cycle threshold (Ct) value (<30 versus ≥30), and by gene positivity (compatible with the B.1.1.7 variant versus not).ResultsOdds of new SARS-CoV-2 infection were reduced 65% (95% CI 60 to 70%; P<0.001) in those ≥21 days since first vaccination with no second dose versus unvaccinated individuals without evidence of prior infection (RT-PCR or antibody). In those vaccinated, the largest reduction in odds was seen post second dose (70%, 95% CI 62 to 77%; P<0.001).There was no evidence that these benefits varied between Oxford-AstraZeneca and Pfizer-BioNTech vaccines (P>0.9).There was no evidence of a difference in odds of new SARS-CoV-2 infection for individuals having received two vaccine doses and with evidence of prior infection but not vaccinated (P=0.89). Vaccination had a greater impact on reducing SARS-CoV-2 infections with evidence of high viral shedding Ct<30 (88% reduction after two doses; 95% CI 80 to 93%; P<0.001) and with self-reported symptoms (90% reduction after two doses; 95% CI 82 to 94%; P<0.001); effects were similar for different gene positivity patterns.ConclusionVaccination with a single dose of Oxford-AstraZeneca or Pfizer-BioNTech vaccines, or two doses of Pfizer-BioNTech, significantly reduced new SARS-CoV-2 infections in this large community surveillance study. Greater reductions in symptomatic infections and/or infections with a higher viral burden are reflected in reduced rates of hospitalisations/deaths, but highlight the potential for limited ongoing transmission from asymptomatic infections in vaccinated individuals.RegistrationThe study is registered with the ISRCTN Registry, ISRCTN21086382.

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Quantitative SARS-CoV-2 anti-spike responses to Pfizer-BioNTech and Oxford-AstraZeneca vaccines by previous infection status

10.1101/2021.03.21.21254061 ◽

2021 ◽

Author(s):

David W Eyre ◽

Sheila F Lumley ◽

Jia Wei ◽

Stuart Cox ◽

Tim James ◽

...

Keyword(s):

Detection Threshold ◽

Vaccine Dose ◽

Additive Models ◽

Antibody Responses ◽

Vaccine Uptake ◽

Antibody Testing ◽

Post Vaccination ◽

Minority Ethnic Groups ◽

Previous Infection ◽

Prior Infection

Objectives We investigate determinants of SARS-CoV-2 anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer-BioNTech or Oxford-AstraZeneca vaccines. Methods HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥50 AU/ml). We used multivariable logistic regression to identify predictors of seropositivity and generalised additive models to track antibody responses over time. Results Vaccine uptake was 80%, but less in lower-paid roles and Black, south Asian and minority ethnic groups. 3570/3610(98.9%) HCWs were seropositive >14 days post-first vaccination and prior to second vaccination, 2706/2720(99.5%) after Pfizer-BioNTech and 864/890(97.1%) following Oxford-AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post-first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after second vaccine were seropositive. Quantitative antibody responses were higher after previous infection: median(IQR) >21 days post-first Pfizer-BioNTech 14,604(7644-22,291) AU/ml vs. 1028(564-1985) AU/ml without prior infection (p<0.001). Oxford-AstraZeneca vaccine recipients had lower readings post-first dose compared to Pfizer-BioNTech, with and without previous infection, 10,095(5354-17,096) and 435(203-962) AU/ml respectively (both p<0.001 vs. Pfizer-BioNTech). Antibody responses post-second vaccination were similar to those after prior infection and one vaccine dose. Conclusions Vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.

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Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines

10.1101/2021.03.25.21254335 ◽

2021 ◽

Author(s):

Nick A Kennedy ◽

Simeng Lin ◽

James R Goodhand ◽

Neil Chanchlani ◽

Nick Powell ◽

...

Keyword(s):

Single Dose ◽

Primary Outcome ◽

Geometric Mean ◽

Antibody Responses ◽

University Hospital ◽

Past Infection ◽

White Ethnicity ◽

Inflammatory Bowel ◽

Multivariable Models ◽

Prior Infection

Background Delayed second-dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single-dose of a SARS-CoV-2 vaccine. Methods Antibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared to a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin a4B7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations 3-10 weeks after vaccination in patients without evidence of prior infection. Secondary outcomes were seroconversion rates, and antibody responses following past infection or a second dose of the BNT162b2 vaccine. Findings Geometric mean [SD] anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL [5.9] vs 28.8 U/mL [5.4] P<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL [4.9]) vs 13.8 U/mL [5.9] P<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab- compared to vedolizumab-treated patients who received the BNT162b2 (fold change [FC] 0.29 [95% CI 0.21, 0.40], p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 [95% CI 0.30, 0.51], p<0.0001) vaccines. In both models, age > 59 years, immunomodulator use, Crohn's disease, and smoking were associated with lower, whilst non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single-dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine. Interpretation Infliximab is associated with attenuated immunogenicity to a single-dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab. Funding Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts. Unrestricted educational grants: F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea) and Galapagos NV (Belgium).

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A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients

10.1101/2021.12.16.21267932 ◽

2021 ◽

Author(s):

Charles Hugo MARQUETTE ◽

Emanuela MARTINUZZI ◽

Jonathan BENZAQUEN ◽

Olivier GUERIN ◽

Sylvie LEROY ◽

...

Keyword(s):

Single Dose ◽

Immune Responses ◽

Vaccine Dose ◽

Antibody Responses ◽

Igg Antibody ◽

Virus Shedding ◽

Booster Injection ◽

Specific Igg ◽

Mucosal Immune Responses ◽

Rna Vaccine

Background: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine. Methods: Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism. Results: In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses Conclusion: This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.

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Measurement of multiple SARS-CoV-2 antibody titer after vaccination represents individual vaccine response and contributes to individually appropriate vaccination schedules

10.1101/2021.05.21.21257575 ◽

2021 ◽

Author(s):

Kenji Ota ◽

Katsunori Yanagihara ◽

Satoshi Murakami ◽

Hiroshi Mukae ◽

Shigeru Kohno

Keyword(s):

Single Dose ◽

Antibody Titer ◽

Underlying Disease ◽

Antibody Responses ◽

Vaccine Response ◽

Before And After ◽

Antibody Dynamics ◽

Prior Infection ◽

Study Monitoring

<Background> mRNA vaccine (BNT162b2) induces antibodies against Spike protein produced by host cell. However, multiple antibody responses before and after vaccination have not been clarified. <Objective> To clarify multiple antibody responses after mRNA vaccination in a variation of individuals including prior infection of COVID-19. <Methods> This is a prospective, observational study, started from March 15th, 2021. IgG and IgM against Receptor Binding Domain (RBD), and IgG against Nucleocapsid protein (N) were measured by chemiluminescence immunoassay (Alinity, Abbott) in the following schedules; before vaccination, and 7, 14, 28 days, 12, 24, 36, 48 weeks after 1st vaccination. <Results> A total of 136 vaccinees (including 23 of those with prior infection) were enrolled in this analysis. Single-dose vaccination in participants with prior infection yielded higher IgG (RBD) response than two-dose vaccination in participants without prior infection (mean ± standard deviation, 31,523 ± 14,332 arbitrary units [AU] per mL vs. 22,461 ± 15,661 AU/mL, P = 0.01). IgM (RBD) response was observed in participants without prior infection at 14 days after the first vaccination, achieving a comparable antibody titer compared with those with prior infection (1.41 ± 1.93 chemiluminescence of Sample / Calibrator [S/C] vs. 1.96 ± 2.49 S/C, P = 0.24). IgG (N) showed its specificity and usefulness to differentiate those with and without prior infection, regardless of vaccination. We investigated the participants without prior infection to analyze antibody response according to backgrounds. IgG (RBD) response was significantly lower in those ≧ 40 years old than those < 40 years old (19,087 ± 14,630 AU/mL vs. 25,334 ± 15,849 AU/mL, P = 0.04) at 28 days after 1st vaccination. Low antibody responses were observed in vaccinees with underlying disease or immunosuppressive therapy. <Conclusion> Multiple antibody dynamics of vaccinees were clarified in this study. Monitoring each person's antibody titer is warranted in public with expected low and high responders. However, we have yet to observe antibody duration of vaccinees. Therefore, effectiveness of single dose vaccination against those with prior infection is not assessed. Antibody titer follow-up study is in progress.

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Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom

Nature Microbiology ◽

10.1038/s41564-021-00947-3 ◽

2021 ◽

Author(s):

Jia Wei ◽

Nicole Stoesser ◽

Philippa C. Matthews ◽

Daniel Ayoubkhani ◽

Ruth Studley ◽

...

Keyword(s):

Single Dose ◽

Latent Class ◽

Latent Class Models ◽

Antibody Responses ◽

Older Individuals ◽

The United Kingdom ◽

Low Responder ◽

Antibody Levels ◽

Prior Infection

AbstractWe report that in a cohort of 45,965 adults, who were receiving either the ChAdOx1 or the BNT162b2 SARS-CoV-2 vaccines, in those who had no prior infection with SARS-CoV-2, seroconversion rates and quantitative antibody levels after a single dose were lower in older individuals, especially in those aged >60 years. Two vaccine doses achieved high responses across all ages. Antibody levels increased more slowly and to lower levels with a single dose of ChAdOx1 compared with a single dose of BNT162b2, but waned following a single dose of BNT162b2 in older individuals. In descriptive latent class models, we identified four responder subgroups, including a ‘low responder’ group that more commonly consisted of people aged >75 years, males and individuals with long-term health conditions. Given our findings, we propose that available vaccines should be prioritized for those not previously infected and that second doses should be prioritized for individuals aged >60 years. Further data are needed to better understand the extent to which quantitative antibody responses are associated with vaccine-mediated protection.

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A single dose ChAdOx1 nCoV-19 vaccine elicits high antibody responses in individuals with prior SARS-CoV-2 infection comparable to that of double dose vaccinated SARS-CoV-2 infection naïve individuals

10.21203/rs.3.rs-1250175/v1 ◽

2022 ◽

Author(s):

Tesfaye Gelanew ◽

Andargachew Mulu ◽

Markos Abebe ◽

Timothy A Bates ◽

Liya Wassie ◽

...

Keyword(s):

Single Dose ◽

Antibody Responses ◽

Double Dose ◽

Igg Antibodies ◽

Igg Antibody ◽

Dose Administration ◽

Post Vaccination ◽

Resource Limited ◽

Antibody Titers ◽

High Level

Abstract Background A single dose COVID-19 vaccines, mostly mRNA-based vaccines, are shown to induce robust antibody responses in individuals who were previously infected with SARS-CoV-2, suggesting the sufficiency of a single dose to those individuals. However, these important data are limited to developed nations and lacking in resource-limited countries, like Ethiopia. Methods We compared receptor-binding domain (RBD)-specific IgG antibodies in 40 SARS-CoV-2 naïve participants and 25 participants previously infected with SARS-CoV-2, who received two doses of ChAdOx1 nCoV-19 vaccine. We measured the antibody response in post-vaccination blood samples from both groups of participants collected at four different post-vaccination time points: 8- and 12-weeks after each dose of the vaccine administration using an in-house developed ELISA. Results We observed a high level of anti-RBD IgG antibodies titers 8-weeks after a single dose administration (16/27; 59.3%) among naïve participants, albeit dropped significantly (p<0.05) two months later, suggesting the protective immunity elicited by the first dose ChAdOx1 nCoV-19 vaccine will likely last for a minimum of three months. However, as expected, a significant (p<0.001) increase in the level of anti-RBD IgG antibodies titers was observed after the second dose administration in all naïve participants. By contrast, the ChAdOx1 nCoV-19 vaccine-induced anti-RBD IgG antibody titers produced by the P.I participants at 8- to 12-weeks post-single dose vaccination were found to be similar to the antibody titers seen after a two-dose vaccination course among infection- naïve participants and showed no significant (p>0.05) increment following the second dose administration. Conclusion Taken together, our findings show that a single ChAdOx1 nCoV-19 dose in previously SARS-CoV-2 infected individuals elicits similar antibody responses to that of double dose vaccinated naïve individuals. Age and sex were not associated with the level of vaccine-elicited immune responses in both individuals with and without prior SARS-CoV-2 infection. Further studies are required to assess the need for a booster dose to extend the duration and amplitude of the specific protective immune response in Ethiopia settings, especially following the Omicron pandemic.

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The impact of SARS-CoV-2 vaccines on antibody responses in the general population in the United Kingdom

10.1101/2021.04.22.21255911 ◽

2021 ◽

Author(s):

Jia Wei ◽

Nicole Stoesser ◽

Philippa C. Matthews ◽

Ruth Studley ◽

Iain Bell ◽

...

Keyword(s):

Single Dose ◽

General Population ◽

Older People ◽

Latent Class ◽

Latent Class Models ◽

Antibody Responses ◽

Older Individuals ◽

Antibody Levels ◽

The Impact ◽

Prior Infection

AbstractReal-world data on antibody response post-vaccination in the general population are limited. 45,965 adults in the UK’s national COVID-19 Infection Survey receiving Pfizer-BioNTech or Oxford-AstraZeneca vaccines had 111,360 anti-spike IgG measurements. Without prior infection, seroconversion rates and quantitative antibody levels post single dose were lower in older individuals, especially >60y. Two doses achieved high responses across all ages, particularly increasing seroconversion in older people, to similar levels to those achieved after prior infection followed by a single dose. Antibody levels rose more slowly and to lower levels with Oxford-AstraZeneca vs Pfizer-BioNTech, but waned following a single Pfizer-BioNTech dose. Latent class models identified four responder phenotypes: older people, males, and those having long-term health conditions were more commonly ‘low responders’. Where supplies are limited, vaccines should be prioritised for those not previously infected, and second doses to individuals >60y. Further data on the relationship between vaccine-mediated protection and antibody responses are needed.

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