Robust antibody responses in 70–80-year-olds 3 weeks after the first or second doses of Pfizer/BioNTech COVID-19 vaccine, United Kingdom, January to February 2021

Sera were collected from 185 adults aged ≥ 70 years in London to evaluate the immune response to COVID-19 vaccines. A single dose of Pfizer/BioNtech vaccine resulted in > 94% seropositivity after 3 weeks in naïve individuals using the Roche Spike antibody assay, while two doses produced very high spike antibody levels, significantly higher than convalescent sera from mild-to-moderate PCR-confirmed adult cases. Our findings support the United Kingdom’s approach of prioritising the first dose and delaying the second dose of COVID-19 vaccine.

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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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Initial SARS-CoV-2 vaccination response can predict booster response for BNT162b2 but not for AZD1222

10.1101/2021.07.06.21260059 ◽

2021 ◽

Author(s):

Thomas Perkmann ◽

Nicole Perkmann-Nagele ◽

Patrick Mucher ◽

Astrid Radakovics ◽

Manuela Repl ◽

...

Keyword(s):

Antibody Responses ◽

Vaccine Response ◽

Antibody Assay ◽

Dependent Effect ◽

Immunosuppressive Medication ◽

Vaccination Response ◽

Vaccine Type ◽

Previous Infection ◽

Anti Body ◽

Antibody Levels

Objectives Our objective was to determine whether SARS-CoV-2 antibody levels after the first dose can predict the final antibody response and whether this is dependent on the vaccine type. Methods 69 BNT162b2 (Pfizer/BioNTech) and 55 AZD1222 (AstraZeneca) vaccinees without previous infection or immunosuppressive medication were included. Anti-body levels were quantified 3 weeks after dose 1, in case of AZD1222 directly before boostering (11 weeks after dose 1) and 3 weeks after dose 2, with the Roche SARS-CoV-2 S total antibody assay. Results Pre-booster (BNT162b2: 80.6 [25.5-167.0] BAU/mL, AZD1222: 56.4 [36.4-104.8] BAU/mL, not significant) and post-booster levels (BNT162b2: 2,092.0 [1,216.3-4,431.8] BAU/mL, AZD1222: 957.0 [684.5-1,684.8] BAU/mL, p<0.0001) correlated well in BNT162b2 (ρ=0.53) but not in AZD1222 recipients. Moreover, antibody levels after the first dose of BNT162b2 correlated inversely with age (ρ=-0.33, P=0.013), whereas a positive correlation with age was observed after the second dose in AZD1222 recipients (ρ=0.26, P=0.030). Conclusions In conclusion, our data suggest that antibody levels quantified by the Roche Elecsys SARS-CoV-2 S assay before the booster shot could infer post-booster responses to BNT162b2, but not to AZ1222. In addition, we found a vaccine-dependent effect on antibody responses, suggesting a possible link between vaccine response and vector immunity.

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A genetic basis for atrophy: dominant non-responsiveness and helicobacter induced gastritis in F1 hybrid mice

Gut ◽

10.1136/gut.45.3.335 ◽

1999 ◽

Vol 45 (3) ◽

pp. 335-340 ◽

Cited By ~ 25

Author(s):

P Sutton ◽

J Wilson ◽

R Genta ◽

D Torrey ◽

A Savinainen ◽

...

Keyword(s):

Immune Response ◽

Serum Antibody ◽

Antibody Responses ◽

Host Factors ◽

Mouse Strains ◽

F1 Hybrid ◽

Helicobacter Felis ◽

Humoral Immune ◽

Antibody Levels ◽

Hybrid Mice

BACKGROUNDThe importance of host factors in helicobacter induced gastritis has been shown in animal models. Infection of most mouse strains withHelicobacter felis results in a functional atrophic gastritis, while other strains remain gastritis free.AIMSTo investigate these host factors further by using genetic crosses of responder and non-responder mice.METHODSF1 hybrids of the non-responder CBA/Ca strain and three strains of mice known to develop H felis induced gastritis were infected for three months with H felis. Gastritis was assessed by histopathology and serum antibody responses by ELISA.RESULTSInfection of CBA/Ca mice and F1 hybrids induced little or no gastritis. Analyses of the antibody responses in these mice revealed virtually undetectable anti-helicobacter antibody levels despite colonisation with high numbers of H felis. In contrast, infection of H felis responsive strains induced gastritis and a significant humoral immune response.CONCLUSIONSThe non-responsiveness of CBA/Ca mice to H felis infection is dominantly inherited. The lack of gastritis in CBA mice and their offspring is probably due to active suppression of the immune response normally mounted against H felis. Investigation of these mechanisms will provide important insights relevant to induction of gastric atrophy and cancer in humans.

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Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment of Plasmodium yoelii Merozoite Surface Protein 1 in Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00397-06 ◽

2007 ◽

Vol 14 (4) ◽

pp. 342-347 ◽

Cited By ~ 12

Author(s):

Pimmada Jeamwattanalert ◽

Yuvadee Mahakunkijcharoen ◽

Leera Kittigul ◽

Pakpimol Mahannop ◽

Sathit Pichyangkul ◽

...

Keyword(s):

Immune Response ◽

Antibody Level ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Plasmodium Yoelii ◽

Antibody Responses ◽

Igg2a Antibody ◽

Igg1 Antibody ◽

Merozoite Surface Protein 1 ◽

Antibody Levels

ABSTRACT Merozoite surface protein 1 (MSP1) is the major protein on the surface of the plasmodial merozoite, and its carboxy terminus, the 19-kDa fragment (MSP119), is highly conserved and effective in induction of a protective immune response against malaria parasite infection in mice and monkeys. However, the duration of the immune response has not been elucidated. As such, we immunized BALB/c mice with a standard four-dose injection of recombinant Plasmodium yoelii MSP119 formulated with Montanide ISA51 and CpG oligodeoxynucleotide (ODN) and monitored the MSP119-specific antibody levels for up to 12 months. The antibody titers persisted constantly over the period of time without significant waning, in contrast to the antibody levels induced by immunization with Freund's adjuvant, where the antibody levels gradually declined to significantly lower levels 12 months after immunization. Investigation of immunoglobulin G (IgG) subclass longevity revealed that only the IgG1 antibody level (Th2 type-driven response) decreased significantly by 6 months, while the IgG2a antibody level (Th1 type-driven response) did not change over the 12 months after immunization, but the boosting effect was seen in the IgG1 antibody responses but not in the IgG2a antibody responses. After challenge infection, all immunized mice survived with negligibly patent parasitemia. These findings suggest that protective immune responses to MSP119 following immunization using oil-based Montanide ISA51 and CpG ODN as an adjuvant are very long-lasting and encourage clinical trials for malaria vaccine development.

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Durability of antibody responses elicited by a single dose of Ad26.COV2.S and substantial increase following late boosting

10.1101/2021.08.25.21262569 ◽

2021 ◽

Cited By ~ 4

Author(s):

Jerald Sadoff ◽

Mathieu Le Gars ◽

Vicky Cardenas ◽

Georgi Shukarev ◽

Nathalie Vaissiere ◽

...

Keyword(s):

Clinical Trial ◽

Single Dose ◽

Booster Dose ◽

Age Groups ◽

Neutralizing Antibody ◽

Primary Vaccination ◽

Antibody Responses ◽

Binding Antibody ◽

Antibody Levels ◽

The Impact

AbstractBackgroundWe evaluated the durability of SARS-CoV-2 antibody levels elicited by the single dose Janssen COVID-19 vaccine, Ad26.COV2.S, and the impact on antibody responses of boosting with Ad26.COV2.S after 6 months in clinical trial participants.MethodsSpike-binding antibody and SARS-CoV-2 neutralizing antibody levels elicited by a single-dose Ad26.COV2.S (5×1010 viral particles [vp]) primary regimen and booster doses (5×1010 vp and 1.25×1010 vp) were assessed by ELISA and wild-type VNA in sera from participants in a Phase 1/2a clinical trial (Cohort 1a, 18–55 years old, N=25; Cohort 2a, 18–55 years old boosted at 6 months, N=17; Cohort 3, ≥65 years old, N=22) and a Phase 2 clinical trial (18–55 and ≥65-year old participants boosted at 6 months, total N=73). Neutralizing antibody levels were determined approximately 8 months after the primary vaccination in participants aged 18–55 years and approximately 9 months in participants aged ≥65 years. Binding antibody levels were evaluated 6 months after primary vaccination and 7- and 28-days after booster doses in both age groups.ResultsA single dose of Ad26.COV2.S elicited neutralizing antibodies that remained largely stable for approximately 8–9 months and binding antibodies that remained stable for at least 6 months irrespective of age group. A 5×1010 vp booster dose at 6 months post prime vaccination in 18–55-year-old adults elicited a steep and robust 9-fold increase at Day 7 post boost compared to Day 29 levels following the initial immunization. A lower booster dose of 1.25×1010 vp at 6 months in adults 18–55 and ≥65 years of age also elicited a rapid and high increase of 6–7.7 fold at Day 28 post boost compared to Day 29 levels following the initial immunization, with similar magnitude of post-boost responses in both age groups.ConclusionsA single dose of Ad26.COV2.S, which demonstrated protection in a Phase 3 efficacy trial, elicited durable neutralizing and binding antibodies for at least 8 and 6 months, respectively, in adults >18 years of age at levels similar to Day 29 responses. A 5×1010 vp or 1.25×1010 vp booster dose at 6 months elicited rapid and robust increases in spike binding antibody levels. The anamnestic responses after booster immunization imply robust immune memory elicited by single-dose Ad26.COV2.S.

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Antibody responses to BNT162b2 mRNA vaccine: infection-naive individuals with abdominal obesity warrant attention

10.1101/2021.09.10.21262710 ◽

2021 ◽

Author(s):

ALEXIS ELIAS MALAVAZOS ◽

Sara Basilico ◽

Gianluca Iacobellis ◽

Valentina Milani ◽

Rosanna Cardani ◽

...

Keyword(s):

Immune Response ◽

Abdominal Obesity ◽

Neutralizing Antibodies ◽

Vaccine Dose ◽

Antibody Responses ◽

Time Points ◽

Trimeric Complex ◽

Antibody Levels ◽

Visceral Adipose ◽

Prior Infection

Objective. The excess of visceral adipose tissue might hinder and delay the immune response. How people with abdominal obesity will respond to mRNA vaccines against SARS-CoV-2 is yet to be established. We evaluated SARS-CoV-2-specific antibody responses after the first and second dose of the BNT162b2 mRNA vaccine comparing the response of individuals affected by abdominal obesity (AO) to those without, discerning between individuals with or without prior infection. Methods. IgG neutralizing antibodies against the Trimeric complex (IgG-TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose-1, at one month and three months after dose-2. Nucleocapsid antibodies were assessed to detect prior SARS-CoV-2 infection. Waist circumference was measured to determine abdominal obesity. Results. Between the first and third month after vaccine dose-2, the drop in IgG-TrimericS levels was more remarkable in individuals with AO compared to those without AO (2.44 fold [95%CI: 2.22-2.63] vs 1.82 fold [95%CI: 1.69-1.92], respectively, p<0.001). Multiple linear regression confirmed this result even when adjusting for possible confounders (p<0.001). Conclusions. Our findings highlight the need to extend the duration of serological monitoring of antibody levels in infection-naive individuals with abdominal obesity, a higher-risk population category in terms of possible weaker antibody response.

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Antibiotics Modulate Vaccine-Induced Humoral Immune Response

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.6.832-837.1999 ◽

1999 ◽

Vol 6 (6) ◽

pp. 832-837 ◽

Cited By ~ 30

Author(s):

Patrick C. Y. Woo ◽

Hoi-Wah Tsoi ◽

Lei-Po Wong ◽

Harry C. H. Leung ◽

Kwok-Yung Yuen

Keyword(s):

Immune Response ◽

T Cell ◽

Antibody Level ◽

Tetanus Toxoid ◽

Humoral Immune Response ◽

Polysaccharide Vaccine ◽

Antibody Responses ◽

Pneumococcal Polysaccharide Vaccine ◽

Humoral Immune ◽

Antibody Levels

ABSTRACT The effects of antibiotics on the antigen-specific humoral immune response are not known. Macrolides, tetracyclines, and beta-lactams are commonly prescribed antibiotics. The first two are known to have immunomodulatory activities. The effects of clarithromycin, doxycycline, and ampicillin on the primary and secondary antibody responses to tetanus toxoid, a pneumococcal polysaccharide vaccine, a hepatitis B virus surface antigen (HBsAg) vaccine, and live attenuatedSalmonella typhi (Ty21a) were investigated using a mouse model. For the mice receiving the tetanus toxoid, the immunoglobulin M (IgM) level of the clarithromycin group at day 7 was significantly lower than the corresponding antibody level of the normal saline (NS) group. For the mice receiving the pneumococcal polysaccharide vaccine, the total antibody and IgM levels of the clarithromycin group and the IgM level of the doxycycline group at day 7 were significantly lower than the corresponding antibody levels of the ampicillin and NS groups. For the mice receiving the HBsAg vaccine, the IgM level of the doxycycline group at day 7 was significantly lower than the corresponding antibody levels of the clarithromycin and NS groups, while the IgM level of the clarithromycin group at day 28 was significantly lower than the corresponding antibody levels of the doxycycline, ampicillin, and NS groups. For the mice receiving all three vaccines, there were no statistically significant differences between any of the antibody levels of the ampicillin group and the corresponding antibody levels of the NS group. For the mice receiving Ty21a, the total antibody levels of the ampicillin group at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Moreover, the IgM levels of the clarithromycin, doxycycline, and ampicillin groups at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Furthermore, the total antibody level of the ampicillin group at day 21 was significantly higher than the corresponding antibody level of the doxycycline group. For all four vaccines, there were no statistically significant differences among the serum levels of interleukin-10 and gamma interferon for the mice treated with the various antibiotics. We conclude that clarithromycin and doxycycline, but not ampicillin, suppress the antibody responses of mice to T-cell-dependent and T-cell-independent antigens, whereas all three antibiotics enhance the antibody response to live attenuated mucosal bacterial vaccines.

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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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SARS-CoV-2 antibody changes in patients receiving COVID-19 convalescent plasma from normal and vaccinated donors

10.1101/2021.07.30.21261339 ◽

2021 ◽

Author(s):

Judith Leon ◽

Anna Merrill ◽

Kai Rogers ◽

Julie Kurt ◽

Spencer Dempewolf ◽

...

Keyword(s):

Antibody Level ◽

Plasma Volume ◽

Single Unit ◽

Antibody Responses ◽

Plasma Samples ◽

High Antibody ◽

Before And After ◽

Antibody Levels ◽

Very High

Background and Objectives: Vaccination has been shown to stimulate remarkably high antibody levels in donors who have recovered from COVID-19. Our objective was to examine patient antibody responses following COVID-19 Convalescent Plasma (CCP) transfusion and compare responses to CCP from vaccinated and nonvaccinated donors. Materials and methods: Plasma samples were obtained from 25 recipients of CCP and COVID-19 antibody levels measured before and after CCP treatment. Factors that effect antibody levels were examined. Results: In the 21 patients who received CCP from nonvaccinated donors, only modest increases in antibody levels were observed. Patients who received two units were more likely to seroconvert than those receiving just one unit. The strongest predictor of changes in patient antibody level was the CCP dose. Using patient plasma volume and donor antibody level, the post-transfusion antibody level could be predicted with remarkable accuracy. In contrast, the 4 patients who received CCP from vaccinated donors all had dramatic increases in antibody levels following transfusion of a single unit. In this subset of recipients, antibody levels observed after transfusion of CCP were comparable to those seen in donors who had fully recovered from COVID-19. Conclusion: If available, CCP from vaccinated donors with very high antibody levels should be used. CCP from vaccinated donors increases patient antibody levels much more than 1 or 2 units of CCP from unvaccinated donors.

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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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