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COVID-19: Infection-Vaccination is the Most Protective Combination Against Reinfection


Electron microscopy visualization of a cell infected with SARS-CoV-2. © Philippe Roingeard, Anne Bull-Maurer, Sonia Georgeault/Inserm.licence CC-BY-NC 4.0 international

A large part of the population has developed immunity against SARS-CoV-2 following infection, vaccination – or both. In addition, some infected patients enjoy “hybrid” immunity when they are vaccinated following their infectious episode. Scientists from Inserm, CNRS, Université Claude-Bernard Lyon 1 and ENS de Lyon at the International Center for Research on Infectious Diseases (CIRI) seek to characterize the imprint left by SARS-CoV-2 exposure through vaccination or the combination of the two events on immune memory. The objective? Deepen their understanding of the mechanisms of immune response to the virus in order to improve patient care and optimize vaccine strategies. In a new study, the scientists compared the immune memory of convalescent individuals, whether or not vaccinated against SARS-CoV-2, with that induced by vaccination in individuals having never been infected with the virus. Their findings show that those who are vaccinated following an infection are the best protected from SARS-CoV-2 reinfection. The full article has been published in Science Translational Medicine.

Our body keeps a memory of the infections it has already fought in order to protect us against possible reinfection. The efficacy of vaccination is based on a strategy of simulating an infection to induce protective immunity, i.e. the production of memory cells “trained” in recognizing the pathogen, which can protect the body in the event of infection.

In the case of COVID-19, immunity is conferred either by infection (natural immunity) or by vaccination (vaccine immunity). Some people also benefit from “hybrid” immunity since they have been vaccinated following an infectious episode.

In order to better understand the precise mechanisms of the immune response to SARS-CoV-2, researchers from Inserm, CNRS, Université Claude-Bernard Lyon 1 and ENS de Lyon compared different immune memory parameters from blood samples collected from individuals with natural immunity, vaccine immunity, or hybrid immunity to SARS-CoV-2.

They focused on the adaptive immune response and more specifically on the so-called “humoral” response (see box below).

More About Adaptive Immune Response

The adaptive immune response is established a few days after contact with the pathogen, unlike the innate immune response, which is immediate.

There are two main categories of adaptive immune response.

Cell responses, which are based on the recognition and destruction of the infected cells by the cytotoxic (killer) T cells.

Humoral responses, which are based on the production of antibodies by the B cells. These antibodies recognize the pathogen and neutralize it to prevent it from infecting the target cells.

Humoral immune memory has two compartments:

– serological memory, estimated by the levels of circulating antibodies produced by the memory plasma cells. These antibodies create a barrier that can prevent reinfection.

– cell memory, consisting of memory B cells that do not secrete antibodies but which can differentiate rapidly and massively into plasma cells to generate a new amplified antibody production. These memory B cells are called upon when the barrier of antibodies produced by the memory plasma cells is deficient or insufficient.

The findings show that six months after the last vaccine injection or after infection, people with hybrid immunity are those with the highest levels of neutralizing antibodies in the blood.

In addition to this quantitative variation in serological memory, the authors also show that hybrid immunity induces a qualitative change in the cell memory constituted by the B cells. This results in a multiplication of the number of certain memory B cells carrying receptors enabling their relocation in the respiratory and intestinal mucosa. This last point suggests that hybrid immunity could provide better protection to the SARS-CoV-2 penetration sites.

“As a whole, the findings of this study demonstrate the superiority of hybrid immunity over all other forms of immunity. They emphasize the importance of including previously infected individuals in vaccination campaigns,” explains Thierry Defrance, Inserm researcher and last author of the study.

“Finally, this study serves as a reminder that while serum antibody levels are certainly an important marker of immunity, they are not the sole determinant of protective immunity. Other components of immune memory, T cells and also memory B cells, may induce a rebound in antibody secretion when stimulated by the virus,” adds the scientist.

Researcher Contact

Thierry Defrance

Inserm researcher

International Center for Research on Infectious Diseases (CIRI)

Nopab (Normal and pathogenic B cells) team

Inserm Unit 1111/Université Claude-Bernard Lyon 1/ENS de Lyon/CNRS

Email: rf.mresni@ecnarfed.yrreiht

Telephone number provided upon request

Press Contact



Prior SARS-CoV-2 infection enhances and reshapes spike protein-specific memory induced by vaccination

Science Translational Medicine, mars 2023

Veronique Barateau1,*, Loic Peyrot1,*, Carla Saade1,*, Bruno Pozzetto1,6,*,Karen Brengel-Pesce3,*, Mad-Helenie Elsensohn4,5, Omran Allatif1, Nicolas Guibert2, Christelle Compagnon3, Natacha Mariano7, Julie Chaix7, Sophia Djebali1, Jean-Baptiste Fassier2, Bruno Lina1,8, Katia Lefsihane1, Maxime Espi1, Olivier Thaunat1, Jacqueline Marvel1, Manuel Rosa-Calatrava1, Andres Pizzorno1, Delphine Maucort-Boulch4,5, Laetitia Henaff1,9, Mitra Saadatian-Elahi1,9, Philippe Vanhems1,9, Stéphane Paul 1,6,$, Thierry Walzer1,$, Sophie Trouillet-Assant1,3,$, and Thierry Defrance1$.

1 CIRI – Centre International de Recherche en Infectiologie, Univ Lyon, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR5308, ENS Lyon, Université Jean Monnet de Saint-Etienne, Lyon, 69007, France.

2 Occupational Health and Medicine Department, Hospices Civils de Lyon, Université Claude Bernard Lyon1, Ifsttar, UMRESTTE, UMR T_9405, Lyon University, Avenue Rockefeller, Lyon, 69008, France.

3 Joint Research Unit Civils Hospices of Lyon-bioMerieux, Civils Hospices of Lyon, Lyon Sud Hospital, Pierre-Benite, 69310, France

4 Hospices Civils de Lyon, Pôle Santé Publique, Service de Biostatistique et Bioinformatique, Lyon, 69003, France.

5 CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, 69100, France.

6 Immunology laboratory, CIC1408, CHU Saint-Etienne, Saint-Etienne, 42055, France.

7 BIOASTER, 40 Avenue Tony 50 Garnier, Lyon, 69007, France

8 Virology laboratory, Institute of Infectious Agents, Laboratory associated with the National Reference Centre for Respiratory Viruses, Hospices Civils de Lyon, Lyon, 69317, France.

9 Service D’Hygiène, Epidémiologie, Infectiovigilance et Prévention, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, 69008, France