Impact of vaccination on the induction of mucosal immunity with mRNA vaccines against the Covid-19 epidemic

Published on 24 April 2024

The essential

Teams from the department of immunology at the Pitié-Salpêtrière AP-HP hospital, Inserm and Sorbonne University, coordinated by Prof Guy Gorochov, have conducted a study into the ability of Covid-19 mRNA vaccines to induce a mucosal immune response. The results of this study were published  JAMA Network Open on 23 April 2024.

The capability of intramuscular mRNA vaccines against SARS-CoV-2 to induce an antibody response in mucous membranes is still debated.

This study, based on the COVICOMPARE-M and COVICOMPARE-P trials, compares the humoral response of individuals vaccinated against Covid-19 with mRNA vaccines. Specifically, the aim is to analyse, at salivary level, the antibody response to vaccination of naïve subjects (not infected by SARS-CoV-2 before or between vaccine shots), compared with that of subjects who were infected before vaccination (pre-infected).

A total of 427 participants were included in the study, 120 of whom were pre-infected. Between February and July 2021, naïve participants received two doses of Moderna or Pfizer-BioNTech vaccine. Pre-infected participants received only one dose of Pfizer vaccine. Samples were collected before the first dose (D1), before the second (D29), then at D57 and at D180.

Salivary SARS-CoV-2 specific IgA antibodies1 were detected to a greater extent in pre-infected subjects than in naïve subjects. However, after vaccination, a small increase in IgA levels was observed in non-pre-infected participants who received the Moderna vaccine. In comparison, IgG antibodies specific to SARS-CoV-2 were widely detected in saliva after vaccination in both naïve and pre-infected subjects. In both cases, IgA and IgG antibody levels measured in saliva were highly correlated with serum levels, indicating a likely diffusion from blood to saliva.

The results of this study show that mRNA vaccination is associated with very low mucosal immunity, but at much lower levels in naïve participants. Further studies are needed to determine the association between specific salivary IgA levels and prevention of SARS-CoV-2 infection or transmission.

The COVICOMPARE-P and COVICOMPARE-M trials have been approved as a National Research Priority by the ad-hoc national steering committee for therapeutic trials and other research into the COVID-19 epidemic (CAPNET). This study was carried out with the scientific and financial support of the ANRS Emerging Infectious Diseases, the Ministry of Health and Prevention and the Ministry of Higher Education, Research and Innovation.

  1. IgA antibodies are mainly found in secretions (saliva, tears, digestive and pulmonary secretions). They are also found in the blood in much smaller quantities than IgG antibodies. Secretory IgA, the predominant form of IgA of the mucosal immune system, is found only in secretions, where it plays a particularly effective antiviral role.

Reference

Guy Gorochov, MD, PhD; Jacques Ropers, PharmD; Odile Launay, MD, PhD; Karim Dorgham, PhD; Omaira da Mata-Jardin, PhD; Said Lebbah, MD; Christine Durier, PhD; Rebecca Bauer, PhD; Anne Radenne, MSc; Corinne Desaint, PhD; Louis-Victorien Vieillard, MSc; Claire Rekacewicz, MSc; Marie Lachatre, MD; Béatrice Parfait, MD, PhD; Frédéric Batteux, MD, PhD; Philippe Hupé, PhD; Läétitia Ninove, MD; Maeva Lefebvre, MD; Anne Conrad, MD, PhD; Bertrand Dussol, MD, PhD; Zoha Maakaroun-Vermesse, MD; Giovanna Melica, MD; Jean-François Nicolas, MD, PhD; Renaud Verdon, MD, PhD; Jean-Jacques Kiladjian, MD, PhD; Paul Loubet, MD, PhD; Catherine Schmidt-Mutter, MD, PhD; Christian Dualé, MD, PhD; Séverine Ansart, MD, PhD; Elisabeth Botelho-Nevers, MD, PhD; Jean-Daniel Lelièvre, MD, PhD; Xavier de Lamballerie, MD, PhD; Marie-Paule Kieny, PhD; Eric Tartour, MD, PhD; Stéphane Paul, PhD – JAMA Network Open

About Inserm:

Founded in 1964, Inserm is a public scientific and technological institute dedicated to biomedical research and human health, and is involved in the entire range of activities from the laboratory to the patient’s bedside. It also partners with the most prestigious research institutions in the world that are committed to scientific challenges and progress in these fields. https://www.inserm.fr/en/home/

 

About ANRS MIE:

The ANRS Emerging Infectious Diseases (MIE), created on 1 January 2021, is an autonomous Inserm agency headed by Professor Yazdan Yazdanpanah. Its remit is to lead, evaluate, coordinate and fund research into HIV/AIDS, viral hepatitis, sexually transmitted infections, tuberculosis and emerging and re-emerging infectious diseases (in particular emerging respiratory infections – including Covid-19 – viral haemorrhagic fevers and arboviruses). Under the authority of the France’s Ministry of Higher Education and Research and Ministry of Health and Prevention, the ANRS MIE federates an interinstitutional network of national and international physicians and researchers, patient organisations and civil society representatives, all fully involved in theagency’s governance and operation. This dynamic co-construction guarantees project implementation in line with the expectations of the affected communities, and aims to limit the health, economic and social impact of epidemics. The Agency’s vaccine research programme is led by the Vaccine Research Institute (VRI). https://anrs.fr/en/

About Sorbonne Université:

Sorbonne University is a multidisciplinary, research-intensive, world-class university covering all the disciplines of the humanities, medicine, science and engineering. Located in the heart of Paris, with a regional presence, Sorbonne University has 55,000 students, 7,300 academic researchers and partner researchers and more than a hundred laboratories. Alongside its partners in the Sorbonne University Alliance, and via its institutes and multidisciplinary initiatives, it conducts and programmes research and training activities to strengthen its collective contribution to the challenges of three major transitions: a global approach to health (One Health), resources for a sustainable planet (One Earth), and changing societies, languages and cultures (One Humanity). Sorbonne Université is also a member of Alliance 4EU+, an innovative European university model that develops strategic international partnerships and promotes openness to the world. https://www.sorbonne-universite.fr/en

About AP-HP:

Europe’s leading university hospital centre (CHU), AP-HP and its 38 hospitals are organised into six university hospital groups (AP-HP. Centre – Université Paris Cité; AP-HP. Sorbonne University; AP-HP. Nord – Université Paris Cité; AP-HP. Université Paris-Saclay; AP-HP. Henri-Mondor University Hospitals and AP-HP. Hôpitaux Universitaires Paris Seine-Saint-Denis) and are structured around five Paris Region universities. In close collaboration with major research organisations, the AP-HP has eight world-class university hospital institutes (ICM, ICAN, IMAGINE, FOReSIGHT, PROMETHEUS, lnovAND, Re-Connect, THEMA) and France’s largest healthcare data warehouse (EDS). A major player in applied research and innovation in healthcare, the AP-HP holds a portfolio of 810 active patents, its clinician-researchers produce more than 11,000 scientific publications every year and nearly 4,400 research projects are currently under development, all sponsors included. In 2020, the AP-HP obtained the Carnot Institute label, which rewards the quality of its partnership research: the Carnot@AP-HP offers applied and clinical research solutions in the field of healthcare to industrial players. In 2015, the AP-HP also set up the Fondation de l’AP-HP, which works directly with healthcare professionals to support the organisation of care, hospital staff and research within the AP-HP. http://www.aphp.fr

 

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