Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients

Hall, Victoria; Ferreira, Victor H; Ku, Terrance; Ierullo, Matthew; Majchrzak-Kita, Beata; Chaparro, Cecilia; Selzner, Nazia; Schiff, Jeffrey; McDonald, Michael; Tomlinson, George; Kulasingam, Vathany; Kumar, Deepali; Humar, Atul

doi:10.1056/nejmc2111462

Cited by 499 publications

(582 citation statements)

References 5 publications

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“…These results follow similar trends expressed in research on the immunogenicity of a homologous three-dose regimen of the CoronaVac vaccine [8, 15], AZD1222 vaccine or mRNA-1273 vaccine [16]. Commonly, it was shown that a third dose evokes a higher immunological response surpassing levels post-second dose of the primary vaccines as a booster effect.…”

Section: Discussionsupporting

confidence: 84%

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults

Yorsaeng¹,

Suntronwong²,

Phowatthanasathian³

et al. 2021

Preprint

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In June 2021, Thailand was hit by the delta variant of SARS-CoV-2 resulting in the biggest wave of COVID-19. Due to the widespread delta variant, more than 600 healthcare workers had COVID-19 despite completion of two-dose CoronaVac. The Ministry of Public Health recommended that healthcare workers received a third dose of AZD1222 to increase level of protection against SARS-CoV-2. However, immune response after the third vaccination with AZD1222 are limited. In this study, sera from those who received a booster of AZD1222 in June-July 2021 were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG, anti-RBD total immunoglobulins and anti-spike protein 1 (S1) IgA. The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern (B.1.1.7, B.1.617.2, and B.1.351) using an enzyme-linked immunosorbent assay-based surrogate virus neutralization test. Participants who received the booster of AZD1222 possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than that two-dose vaccines (p < 0.001). They also elicited higher neutralizing activity against the wild type and all variants of concern than those in the recipients of the two-dose vaccines. This study demonstrated a high immunogenicity of the AZD1222 booster who completed the two-dose inactivated vaccines.

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Section: Discussionsupporting

confidence: 84%

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults

Yorsaeng¹,

Suntronwong²,

Phowatthanasathian³

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…Our current findings raise the question of whether immunosuppressed individuals should be tested for SARS-CoV-2 anti-spike antibody post-vaccination. A recent study indicates that immunization with a third dose of mRNA vaccine boosts the immune response in solid organ transplant recipients [35,36]. More studies are needed to determine the correlates of immunity required to protect from severe COVID-19, and the optimal approaches for eliciting these responses in SOT patients or others undergoing immunosuppressive therapies.…”

Section: Discussionmentioning

confidence: 99%

“…Another limitation of our study is that we did not have evidence of an immune response to the vaccine in our vaccinated subjects. Although the vast majority of healthy individuals respond to the vaccines authorized for emergency use, recent studies suggest that SOT patients may require a third immunization to elicit a detectable antibody response to spike protein [35,36]. Future studies will focus on evaluating the antibody response to vaccination in SOT and other immunocompromised patient populations.…”

Section: Discussionmentioning

confidence: 99%

Breakthrough Infections with Multiple Lineages of SARS-CoV-2 Variants Reveals Continued Risk of Severe Disease in Immunosuppressed Patients

Deng

Evdokimova

O’Brien

et al. 2021

Viruses

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The pandemic of COVID-19 caused by SARS-CoV-2 infection continues to spread around the world. Vaccines that elicit protective immunity have reduced infection and mortality, however new viral variants are arising that may evade vaccine-induced immunity or cause disease in individuals who are unable to develop robust vaccine-induced responses. Investigating the role of viral variants in causing severe disease, evading vaccine-elicited immunity, and infecting vulnerable individuals is important for developing strategies to control the pandemic. Here, we report fourteen breakthrough infections of SARS-CoV-2 in vaccinated individuals with symptoms ranging from asymptomatic/mild (6/14) to severe disease (8/14). High viral loads with a median Ct value of 19.6 were detected in the nasopharyngeal specimens from subjects regardless of disease severity. Sequence analysis revealed four distinct virus lineages, including alpha and gamma variants of concern. Immunosuppressed individuals were more likely to be hospitalized after infection (p = 0.047), however no specific variant was associated with severe disease. Our results highlight the high viral load that can occur in asymptomatic breakthrough infections and the vulnerability of immunosuppressed individuals to post-vaccination infections by diverse variants of SARS-CoV-2.

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“…To date, limited data exist that report on the efficacy and safety of a third vaccine in immunosuppressed patients to guide the vaccination strategy on non-seroconverted patients, particularly those at high risk for severe Covid-19 infections. Data published so far report on increased immunogenicity of a third vaccine in patients with solid organ transplantations 6–8 . However, most of the patients included in these trials had already shown some humoral response, as evidenced by the inclusion criteria, which allowed for the presence of low antibody levels against SARS-CoV-2 after two vaccinations.…”

Section: Discussionmentioning

confidence: 99%

“…However, immune responses to these vaccines vary between individuals and antibody levels wane over time 3,4 . Application of an additional booster dose is heavily investigated by ongoing clinical trials and first reports have been published 5–8 . Several countries already started a third vaccination, especially in patients at high risk.…”

mentioning

confidence: 99%

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

Bonelli

Mrak

Tobudic

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus–2 (SARS–CoV–2)–induced coronavirus disease 2019 (COVID–19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID–19 vaccination. In this blinded randomized clinical trial (EudraCT 2021–002348–57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non–seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA–1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV–19 (Oxford–AstraZeneca). Patients were stratified according to the presence of peripheral B–cells. The primary efficacy endpoint was the difference in the SARS–CoV–2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four. Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T–cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non–seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

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Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients

Cited by 499 publications

References 5 publications

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults

Breakthrough Infections with Multiple Lineages of SARS-CoV-2 Variants Reveals Continued Risk of Severe Disease in Immunosuppressed Patients

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

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