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Real-World Serologic Responses to Extended-Interval and Heterologous COVID-19 mRNA Vaccination in Frail Elderly - Interim Report from a Prospective Observational Cohort Study

24 Pages Posted: 22 Sep 2021

See all articles by Donald C. Vinh

Donald C. Vinh

McGill University - Infectious Diseases and Immunity in Global Health Program

Jean-Philippe Gouin

Centre de Recherche de l'Institut Universitaire de Gériatrie Montréal (CRIUGM); Concordia University, Quebec

Diana Cruz-Santiago

Centre de Recherche de l'Institut Universitaire de Gériatrie Montréal (CRIUGM)

Michelle Canac-Marquis

McGill University - Infectious Diseases and Immunity in Global Health Program

Stéphane Bernier

McGill University - Infectious Diseases and Immunity in Global Health Program

Florian Bobeuf

Centre de Recherche de l'Institut Universitaire de Gériatrie Montréal (CRIUGM)

Avik Sengupta

McGill University - Infectious Diseases and Immunity in Global Health Program

Jean-Philippe Brassard

McGill University - Infectious Diseases and Immunity in Global Health Program

Alyssa Guerra

McGill University - Infectious Diseases and Immunity in Global Health Program

Robert Dziarmaga

McGill University - Infectious Diseases and Immunity in Global Health Program

Anna Perez

McGill University - Infectious Diseases and Immunity in Global Health Program

Yichun Sun

McGill University - Infectious Diseases and Immunity in Global Health Program

Yongbiao Li

McGill University - Infectious Diseases and Immunity in Global Health Program

Lucie Roussel

McGill University - Infectious Diseases and Immunity in Global Health Program

Mélanie J. Langelier

McGill University - Infectious Diseases and Immunity in Global Health Program

Danbing Ke

McGill University - Meakins-Christie Laboratories

Corey Arnold

University of Ottawa - Department of Biochemistry, Microbiology and Immunology

Martin Pelchat

University of Ottawa - Department of Biochemistry, Microbiology and Immunology

Marc-André Langlois

University of Ottawa - Department of Biochemistry, Microbiology and Immunology

Timothy Grant Evans

McGill University - School of Population and Global Health

Xun Zhang

McGill University - Centre for Outcomes Research and Evaluation

Bruce D. Mazer

McGill University - Meakins-Christie Laboratories

COVID-19 Immunity Task Force and UNCoVER Investigators

Independent

More...

Abstract

Background: The Coronavirus disease 2019 (Covid-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has prompted accelerated vaccines development. Their use was prioritized to protect the most vulnerable, notably, the elderly. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been employed. The effectiveness of these strategies in the frail elderly are unknown.

Methods: In this real-world vaccination study, under a government-decreed rationing strategy, elderly adults residing in long-term care facilities, with or without previously-documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. Clinical data and blood were serially collected during and after this interval period. Sera were tested for SARS-CoV-2-specific IgG antibodies (to trimeric S; RBD; nucleocapsid) by automated chemiluminescent ELISA. 

Findings: After a significant increase 4 weeks post-prime dose, there was a significant decline in anti-RBD and anti-S IgG levels until the boost dose, followed by an increase 4 weeks later. Previously uninfected individuals exhibited lower antibody responses up to 16 weeks post-prime dose, but achieved comparable levels to previously infected counterparts by 4 weeks post-second dose. Individuals primed with BNT162b2 exhibited larger decrease in anti-RBD and anti-S IgG levels with 16-week interval between doses, compared to those who received mRNA-1273. No differences in antibody levels 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations.

Interpretations: These interim results of this ongoing longitudinal study show that, among frail elderly, neither age, sex, nor comorbidity affect antigenicity of mRNA-based COVID vaccines, but previous SARS-CoV-2 infection and type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. Homologous/heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following second dose, supporting their interchangeability.

Funding: This project was supported by funding from the Public Health Agency of Canada, through the Vaccine Surveillance Reference group and the COVID-19 Immunity Task Force (CITF).

Declaration of Interest: None to declare.

Ethical Approval: This study was conducted in 12 LTC facilities of the Montréal Centre-
Sud – Integrated University Health and Social Services Centre (CIUSSS du Centre-Sud-de-l'Île-de-
Montréal) and was approved by its research ethics board (Comité d'éthique de la recherche
Vieillissement-Neuroimagerie, protocol number 20-21-36 MP).

Keywords: COVID-19, SARS-CoV-2, mRNA-1273, BNT162b2, antibody responses, frail elderly

Suggested Citation

Vinh, Donald C. and Gouin, Jean-Philippe and Gouin, Jean-Philippe and Cruz-Santiago, Diana and Canac-Marquis, Michelle and Bernier, Stéphane and Bobeuf, Florian and Sengupta, Avik and Brassard, Jean-Philippe and Guerra, Alyssa and Dziarmaga, Robert and Perez, Anna and Sun, Yichun and Li, Yongbiao and Roussel, Lucie and Langelier, Mélanie J. and Ke, Danbing and Arnold, Corey and Pelchat, Martin and Langlois, Marc-André and Evans, Timothy Grant and Zhang, Xun and Mazer, Bruce D. and Investigators, COVID-19 Immunity Task Force and UNCoVER, Real-World Serologic Responses to Extended-Interval and Heterologous COVID-19 mRNA Vaccination in Frail Elderly - Interim Report from a Prospective Observational Cohort Study. Available at SSRN: https://ssrn.com/abstract=3927745 or http://dx.doi.org/10.2139/ssrn.3927745

Donald C. Vinh (Contact Author)

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Jean-Philippe Gouin

Centre de Recherche de l'Institut Universitaire de Gériatrie Montréal (CRIUGM) ( email )

Montréal
Canada

Concordia University, Quebec ( email )

1455 de Maisonneuve Blvd. W.
Montreal, Quebec H3G 1MB
Canada
+1-514-848-2424 # 7538 (Phone)

Diana Cruz-Santiago

Centre de Recherche de l'Institut Universitaire de Gériatrie Montréal (CRIUGM) ( email )

Montréal
Canada

Michelle Canac-Marquis

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Stéphane Bernier

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Florian Bobeuf

Centre de Recherche de l'Institut Universitaire de Gériatrie Montréal (CRIUGM) ( email )

Montréal
Canada

Avik Sengupta

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Jean-Philippe Brassard

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Alyssa Guerra

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Robert Dziarmaga

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Anna Perez

McGill University - Infectious Diseases and Immunity in Global Health Program

Montreal
Canada

Yichun Sun

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Yongbiao Li

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Lucie Roussel

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Mélanie J. Langelier

McGill University - Infectious Diseases and Immunity in Global Health Program ( email )

Montreal
Canada

Danbing Ke

McGill University - Meakins-Christie Laboratories ( email )

Montreal
Canada

Corey Arnold

University of Ottawa - Department of Biochemistry, Microbiology and Immunology

Ottawa
Canada

Martin Pelchat

University of Ottawa - Department of Biochemistry, Microbiology and Immunology ( email )

Ottawa
Canada

Marc-André Langlois

University of Ottawa - Department of Biochemistry, Microbiology and Immunology ( email )

Ottawa
Canada

Timothy Grant Evans

McGill University - School of Population and Global Health ( email )

Montreal, Quebec
Canada

Xun Zhang

McGill University - Centre for Outcomes Research and Evaluation

Montreal
Canada

Bruce D. Mazer

McGill University - Meakins-Christie Laboratories ( email )

Montreal
Canada