scholarly journals SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings From The COV-AD Study

2022 ◽  
Author(s):  
Adrian M Shields ◽  
Sian E. Faustini ◽  
Harriet J. Hill ◽  
Saly Al-Taei ◽  
Chloe Tanner ◽  
...  
Keyword(s):  
Recurrent Infection ◽  
Cellular Responses ◽  
Antibody Deficiency ◽  
Breakthrough Infection ◽  
Live Virus ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Interferon Gamma Release Assays ◽  
Antibody Levels

Abstract Background Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives COVID in patients with antibody deficiency (COV-AD) is a multi-site United Kingdom study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods Individuals on immunoglobulin replacement therapy or with an IgG less than 4g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results 5.6% (n=320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n=168) compared with 100% of healthy controls (n=205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs 48.0%, p=0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs 2.39, p=0.0003). T cell responses post vaccination were demonstrable in 46.2% of participants, were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

scholarly journals mRNA COVID-19 vaccines induce enhanced antibody and cellular responses compared to ChAdOx1 or natural infection in children

2021 ◽  
Author(s):  
Alexander Dowell ◽  
Annable Powell ◽  
Chris Davis ◽  
Brian Willett ◽  
Rachel Bruton ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Infection ◽  
Cellular Responses ◽  
Effector Memory ◽  
Live Virus ◽  
Cell Responses ◽  
Antibody Titres ◽  
Antibody Levels ◽  
Optimal Protection

Abstract We present a comprehensive analysis of antibody and cellular responses in children aged 12-16 years who received COVID-19 vaccination with ChAdOx1 (n=6) or mRNA vaccine (mRNA-1273 or BNT162b2, n=9) using a 12-week extended-interval schedule. mRNA vaccination of seropositive children induces high antibody levels, with one dose, but a second dose is required in infection-naïve children. Following a second ChAdOx1 dose, antibody titres were higher than natural infection, but lower than mRNA vaccination. Vaccination induced live virus neutralising antibodies against Alpha, Beta and Delta variants, however, a second dose is required in infection-naïve children. We found higher T-cell responses following mRNA vaccination than ChAdOx1. Phenotyping of responses showed predominantly early effector-memory CD4 T cell populations, with a type-1 cytotoxic cytokine signature, with IL-10. These data demonstrate mRNA vaccination induces a co-ordinated superior antibody and robust cellular responses in children. Seronegative children require a prime-boost regime for optimal protection.

scholarly journals Differential Immunogenicity of BNT162b2 or ChAdOx1 Vaccines After Extended-Interval Homologous Dual Vaccination in Older People

2021 ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n=54) or ChAdOx1 (n=77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-g ELISpot. ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5- 2543) in the 74 patients after the ChAdOx1 vaccine (p=<0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p=0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.7-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas W. McDade ◽  
Alexis R. Demonbreun ◽  
Amelia Sancilio ◽  
Brian Mustanski ◽  
Richard T. D’Aquila ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Messenger Rna ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
Clinical Protection ◽  
Exposure History ◽  
Antibody Levels

AbstractTwo-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.

scholarly journals Reduced seroconversion in children compared to adults with mild COVID-19

2021 ◽  
Author(s):  
Zheng Quan Toh ◽  
Jeremy Anderson ◽  
Nadia Mazarakis ◽  
Melanie Neeland ◽  
Rachel A Higgins ◽  
...  
Keyword(s):  
Immune Response ◽  
Throat Swab ◽  
Cellular Responses ◽  
Lower Proportion ◽  
Blood Samples ◽  
Viral Loads ◽  
Vaccine Responses ◽  
Pcr Diagnosis ◽  
Antibody Levels ◽  
Age And Sex

Importance: The immune response in children with SARS-CoV-2 infection is not well understood. Objective: To compare seroconversion in children and adults with non-hospitalized (mild) SARS-CoV-2 infection and to understand the factors that influence this. Design: Participants were part of a household cohort study of SARS-CoV-2 infection. Weekly nasopharyngeal/throat swabs and blood samples were collected during the acute and convalescent period following PCR diagnosis for analysis. Setting: Participants were recruited at the Royal Childrens Hospital, Melbourne, Australia between May and October 2020. Participants: Those who had a SARS-CoV-2 PCR-positive nasal/throat swab. Main outcomes and measures: SARS-CoV-2 antibody and cellular responses in children and adults. Seroconversion was defined by seropositivity in all three serological assays. Results: Among 108 SARS-CoV-2 PCR-positive participants, 57 were children (median age: 4, IQR 2-10) and 51 were adults (median age: 37, IQR 34-45). Using three established serological assays, a lower proportion of children seroconverted compared with adults [20/54 69 (37.0%) vs 32/42 (76.2%); (p<0.001)]. This was not related to viral load, which was similar in children and adults [mean Ct 28.58 (SD: 6.83) vs 24.14 (SD: 8.47)]. Age and sex also did not influence seroconversion or the magnitude of antibody response within children or adults. Notably, in adults (but not children) symptomatic adults had three-fold higher antibody levels than asymptomatic adults (median 227.5 IU/mL, IQR 133.7-521.6 vs median 75.3 IU/mL, IQR 36.9-113.6). Evidence of cellular immunity was observed in adults who seroconverted but not in children who seroconverted. Conclusion and Relevance: In this non-hospitalized cohort with mild COVID-19, children were less likely to seroconvert than adults despite similar viral loads. This has implications for future protection following COVID-19 infection in children and for interpretation of serosurveys that involve children. Further research to understand why children are less likely to seroconvert and develop symptoms following SARS-CoV-2 infection, and comparison with vaccine responses may be of clinical and scientific importance.

scholarly journals Spike-Directed Vaccination Elicits Robust Spike-Specific T cell Responses Including to Mutant Strains

2021 ◽  
Author(s):  
Maja Stanojevic ◽  
Ashley Geiger ◽  
Brita Ostermeier ◽  
Danielle Sohai ◽  
Christopher Lazarski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Reference Strain ◽  
Critical Role ◽  
T Cell Responses ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Mutant Strains ◽  
Before And After

Abstract While most studies describing COVID-19 vaccine responses have focused on antibodies, there is increasing evidence that T cells play a critical role. Here we evaluated T cell responses in seronegative donors before and after vaccination to define responses to SARS-CoV-2 reference strain, as well as to mutations in the variant strains B.1.1.7 and B.1.351. We observed enhanced T cell responses to reference and variant Spike strains post vaccination.

scholarly journals Differential immunogenicity of BNT162b2 or ChAdOx1 vaccines after extended-interval homologous dual vaccination in older people

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Helen Parry ◽  
Rachel Bruton ◽  
Christine Stephens ◽  
Kevin Brown ◽  
Gayatri Amirthalingam ◽  
...  
Keyword(s):  
Immune Responses ◽  
Older People ◽  
Natural Infection ◽  
Cellular Responses ◽  
Antibody Responses ◽  
Vaccine Responses ◽  
Cell Responses ◽  
Boost Vaccine ◽  
The Uk ◽  
Cellular Immune

Abstract Background Several SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8–12 week ‘extended interval’. Objectives We undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2–3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot. Results Antibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892–8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5–2543) in the 74 patients after the ChAdOx1 vaccine (p = < 0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p = 0.022). Conclusion Dual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.4-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

scholarly journals Dichotomy between the humoral and cellular responses elicited by mRNA and adenoviral vector vaccines against SARS-CoV-2

2021 ◽  
Author(s):  
Rahul Ukey ◽  
Natalie Bruiners ◽  
Hridesh Mishra ◽  
Pankaj K. Mishra ◽  
Deborah McCloskey ◽  
...  
Keyword(s):  
Single Dose ◽  
Adenoviral Vector ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Cellular Responses ◽  
Real World Data ◽  
Symptomatic Infection ◽  
Cell Responses ◽  
Binding Antibody ◽  
Antibody Levels

AbstractProtection from severe disease and hospitalization by SARS-CoV-2 vaccination has been amply demonstrated by real-world data. However, the rapidly evolving pandemic raises new concerns. One pertains efficacy of adenoviral vector-based vaccines, particularly the single-dose Ad26.COV2.S, relative to mRNA vaccines. We investigated the immunogenicity of Ad26.COV2.S and mRNA vaccines in 33 subjects vaccinated with either vaccine class five months earlier on average. After controlling for time since vaccination, Spike-binding antibody and neutralizing antibody levels were higher in the mRNA-vaccinated subjects, while no significant differences in antigen-specific B cell and T cell responses were observed between the two groups. Thus, a dichotomy exists between humoral and cellular responses elicited by the two vaccine classes. Our results have implications for the need of booster doses in vaccinated subjects and might explain the dichotomy reported between the waning protection from symptomatic infection by SARS-CoV-2 vaccination and its persisting efficacy in preventing hospitalization and death.

scholarly journals COVID-19 vaccination and antirheumatic therapy

Rheumatology ◽  
2021 ◽  
Author(s):  
Jack Arnold ◽  
Kevin Winthrop ◽  
Paul Emery
Keyword(s):  
Immunosuppressive Therapy ◽  
Management Strategy ◽  
Humoral Response ◽  
Vaccine Response ◽  
Antirheumatic Therapy ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
History Of ◽  
Humoral Responses ◽  
Existing Data

Abstract The coronavirus disease 2019 (COVID-19) vaccination will be the largest vaccination programme in the history of the NHS. Patients on immunosuppressive therapy will be among the earliest to be vaccinated. Some evidence indicates immunosuppressive therapy inhibits humoral response to the influenza, pneumococcal and hepatitis B vaccines. The degree to which this will translate to impaired COVID-19 vaccine responses is unclear. Other evidence suggests withholding MTX for 2 weeks post-vaccination may improve responses. Rituximab has been shown to impair humoral responses for 6 months or longer post-administration. Decisions on withholding or interrupting immunosuppressive therapy around COVID-19 vaccination will need to be made prior to the availability of data on specific COVID-19 vaccine response in these patients. With this in mind, this article outlines the existing data on the effect of antirheumatic therapy on vaccine responses in patients with inflammatory arthritis and formulates a possible pragmatic management strategy for COVID-19 vaccination.

scholarly journals Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates

2021 ◽  
Vol 7 (22) ◽  
pp. eabg7156
Author(s):  
So-Hee Hong ◽  
Hanseul Oh ◽  
Yong Wook Park ◽  
Hye Won Kwak ◽  
Eun Young Oh ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
Statistical Significance ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Antibody Levels ◽  
Further Development

Since the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), various vaccines are being developed, with most vaccine candidates focusing on the viral spike protein. Here, we developed a previously unknown subunit vaccine comprising the receptor binding domain (RBD) of the spike protein fused with the tetanus toxoid epitope P2 (RBD-P2) and tested its efficacy in rodents and nonhuman primates (NHPs). We also investigated whether the SARS-CoV-2 nucleocapsid protein (N) could increase vaccine efficacy. Immunization with N and RBD-P2 (RBDP2/N) + alum increased T cell responses in mice and neutralizing antibody levels in rats compared with those obtained using RBD-P2 + alum. Furthermore, in NHPs, RBD-P2/N + alum induced slightly faster SARS-CoV-2 clearance than that induced by RBD-P2 + alum, albeit without statistical significance. Our study supports further development of RBD-P2 as a vaccine candidate against SARS-CoV-2. Also, it provides insights regarding the use of N in protein-based vaccines against SARS-CoV-2.

scholarly journals Determinants of Protection Against Measles Infection in a Vaccinated Healthcare Worker

2020 ◽  
Vol 41 (S1) ◽  
pp. s185-s185
Author(s):  
Annie St-Pierre ◽  
Anne-Marie Charron ◽  
Pamela Doyon-Plourde ◽  
Caroline Quach
Keyword(s):  
Vaccination Status ◽  
Secondary Case ◽  
Enzyme Linked Immunosorbent Assay ◽  
Demographic Information ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Equivocal Result ◽  
Commercial Enzyme Immunoassay ◽  
Antibody Levels ◽  
Care Worker

Background: In 2019, a measles community outbreak resulted in a secondary case in a health care worker (HCW) working in a pediatric hospital in Montral, Canada. Following the event, HCWs were screened to identify individuals susceptible to measles infection based on serology results. Objective: Our aim was to assess measles seroprotection rates and to evaluate vaccine responses of susceptible HCWs using commercial enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA). Methods: Emergency department (ED) employees, including doctors, were screened for measles susceptibility as part of a postoutbreak measure by the hospital occupational health service. Demographic information was collected. Measles history and vaccination information were collected using a personal vaccination booklet, employee vaccination profile, or the Qubec vaccination registry. According to the Quebec Immunization Protocol (PIQ), individuals born before 1970, or who have received 2 doses of a measles-containing vaccines are considered protected. Individuals with undetectable or equivocal antibody levels were considered at risk of measles infection. These individuals were offered vaccination and were tested for vaccine response 4 weeks after vaccination. Results: Anti-IgG measles antibody results, demographic information, and vaccination information were obtained for 257 employees. The results are currently available for 233 HCWs: 224 HCWs (96%) were seropositive, 7 (3%) were seronegative, and 2 were equivocal. Among seronegative individuals, 6 (85.7%) were born after 1980 and 3 (42.9%) had received 2 doses of a measles-containing vaccine. Of those with an equivocal result, 1 (50%) had received 2 doses and 1 (50%), born after 1970, did not confirm vaccination status. Finally, 9 (4%) of seropositive individuals were not vaccinated; of whom 8 (88.9%) were born before 1970. Conclusions: Our preliminary results suggest that the 95% immunity threshold that is usually required to prevent secondary transmission of measles has been reached in our ED HCW cohort. Even years after the second MMR dose, HCWs remain well protected. Relying on documented vaccination status is thus acceptable.Funding: NoneDisclosures: None

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