[Viruses to rescue health: Vaccination]. / Les virus au service de la santé : la vaccination.

Viruses have been used as tools to prevent viral infections themselves for more than two centuries with impressive success. After the empirical discoveries of the first vaccines, today the development of genetic engineering, molecular virology, reverse genetics, the manipulation of viral genomes, their high-throughput sequencing and their chemical synthesis, the mastery of cell culture and purification methods have greatly benefited the development of viral vaccines. Since smallpox and rabies, the history of vaccinology has followed in the footsteps of the history of virology. New mRNA or viral vector vaccines have emerged in recent years. They were developed and distributed to the population in record time in the face of the Covid pandemic. Viruses in the service of health have a bright future ahead of them, whether to prevent other pandemics, to treat cancer, or to finally control HIV and malaria.

Title: Les virus au service de la santé : la vaccination. Abstract: Depuis plus de deux siècles, les virus sont utilisés, avec un succès impressionnant, comme outils de prévention des infections virales. Depuis la variole et la rage, l'histoire de la vaccinologie a suivi les pas de l'histoire de la virologie. Après les découvertes empiriques des premiers vaccins, le développement du génie génétique, de la virologie moléculaire, de la génétique inverse, la manipulation des génomes viraux, leur séquençage à haut débit et leur synthèse chimique, la maîtrise de la culture cellulaire et des méthodes de purification, ont considérablement contribué au développement de nouveaux vaccins viraux. Des vaccins à ARN messager ou à vecteur viral ont ainsi vu le jour ces dernières années et, face à la pandémie de Covid-19, ont été développés et distribués à la population en un temps record. Les virus au service de la santé ont un bel avenir devant eux, que cela soit pour prévenir d'autres pandémies, pour traiter le cancer, ou contrôler, enfin, le VIH ou le Plasmodium, l'agent du paludisme.

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders.

Introduction: Current approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission. Methods: We measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer). Results: While serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19. Discussion: As breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.

Role and Limits of COVID-19 Vaccines in the Delicate Transition from Pandemic Mitigation to Endemic Control.

The recent surge of COVID-19 related to the Omicron variant emergence has thrown a harsh light upon epidemic control in the near future. This should lead the scientific and medical community to question the long-term vaccine strategy for SARS-CoV-2 control. We provide here a critical point of view regarding the virological evolution, epidemiological aspects, and immunological drivers for COVID-19 control, including a vaccination strategy. Overall, we need more innovations in vaccine development to reduce the COVID-19 burden long term. The most adequate answer might be better cooperation between universities, biotech and pharmaceutical companies.

Investigation of a COVID-19 outbreak on the Charles de Gaulle aircraft carrier, March to April 2020: a retrospective cohort study.

BackgroundSARS-CoV-2 emergence was a threat for armed forces. A COVID-19 outbreak occurred on the French aircraft carrier Charles de Gaulle from mid-March to mid-April 2020.AimTo understand how the virus was introduced, circulated then stopped circulation, risk factors for infection and severity, and effectiveness of preventive measures.MethodsWe considered the entire crew as a cohort and collected personal, clinical, biological, and epidemiological data. We performed viral genome sequencing and searched for SARS-CoV-2 in the environment.ResultsThe attack rate was 65% (1,148/1,767); 1,568 (89%) were included. The male:female ratio was 6.9, and median age was 29 years (IQR: 24-36). We examined four clinical profiles: asymptomatic (13.0%), non-specific symptomatic (8.1%), specific symptomatic (76.3%), and severe (i.e. requiring oxygen therapy, 2.6%). Active smoking was not associated with severe COVID-19; age and obesity were risk factors. The instantaneous reproduction rate (Rt) and viral sequencing suggested several introductions of the virus with 4 of 5 introduced strains from within France, with an acceleration of Rt when lifting preventive measures. Physical distancing prevented infection (adjusted OR: 0.55; 95% CI: 0.40-0.76). Transmission may have stopped when the proportion of infected personnel was large enough to prevent circulation (65%; 95% CI: 62-68).ConclusionNon-specific clinical pictures of COVID-19 delayed detection of the outbreak. The lack of an isolation ward made it difficult to manage transmission; the outbreak spread until a protective threshold was reached. Physical distancing was effective when applied. Early surveillance with adapted prevention measures should prevent such an outbreak.

[Exploration of vaccine immunogenicity]. / L'exploration de l'immunogénicité vaccinale.

The development of new vaccines has traditionally been a long-term job, although recent experience with the emergence of Covid-19 has caused development and production delays to skyrocket. The fact remains that the development of vaccines in the preclinical phases and in phases 1 and 2 of clinical development is based on the study of the specific immune response of the adaptive immune system.

L’exploration de l’immunogénicité vaccinale Exploration of vaccine immunogenicity

Résumé Le développement de nouveaux vaccins était traditionnellement un travail de longue haleine, même si l’expérience récente de l’émergence de la Covid-19 a fait exploser les délais de développement et de production. Il n’en reste pas moins que le développement des vaccins dans les phases précliniques et les phases 1 et 2 de développement clinique est basé sur l’étude de la réponse immunitaire spécifique du système immunitaire adaptatif.

Neutralizing antibody response to SARS-CoV-2 persists 9 months post symptom onset in mild and asymptomatic patients.

OBJECTIVE: A better understanding of the immune response against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is critical to predict its dynamics within the general population and its impact on the vaccination strategy. This study assessed the persistence of neutralizing antibody (Nab) activity and SARS-CoV-2 serology in serum samples of mild and asymptomatic patients 9 months post symptom onset (PSO) in a primary care context among immunocompetent adults. METHODS: A longitudinal cohort of crew members (CMs) exposed to coronavirus disease 2019 (COVID-19) during an outbreak of SARS-CoV-2 on the French aircraft carrier 'Charles de Gaulle' in April 2020 was created. CMs infected with COVID-19 and with positive serology at the end of quarantine were tested 9 months PSO. Samples were collected 18 and 280 days PSO. For each patient, both serology and serum viral neutralizing activity were performed. RESULTS: In total, 86 CMs were analysed. Samples were collected 18 and 280 days PSO. The seroconversion rates were 100% and 93% (82/86) at 18 and 280 days PSO, respectively, and 72.7% of patients exhibited persistent Nab activity at 9 months, regardless of disease severity. CONCLUSION: Nab activity persists for up to 9 months following asymptomatic/mild COVID-19 among young adults, regardless of serological results.

A live measles-vectored COVID-19 vaccine induces strong immunity and protection from SARS-CoV-2 challenge in mice and hamsters.

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2.

Differential serological and neutralizing antibody dynamics after an infection by a single SARS-CoV-2 strain.

BACKGROUND: We report here the case of two coworkers infected by the same SARS-CoV-2 strain, presenting two different immunological outcomes. CASE: One patient presented a strong IgG anti-receptor-binding domain immune response correlated with a low and rapidly decreasing titer of neutralizing antibodies. The other patient had a similar strong IgG anti-receptor-binding domain immune response but high neutralizing antibody titers. DISCUSSION AND CONCLUSION: Thus, host individual factors may be the main drivers of the immune response varying with age and clinical severity.

Virus Eradication and Synthetic Biology: Changes with SARS-CoV-2?

The eradication of infectious diseases has been achieved only once in history, in 1980, with smallpox. Since 1988, significant effort has been made to eliminate poliomyelitis viruses, but eradication is still just out of reach. As the goal of viral disease eradication approaches, the ability to recreate historically eradicated viruses using synthetic biology has the potential to jeopardize the long-term sustainability of eradication. However, the emergence of the severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 pandemic has highlighted our ability to swiftly and resolutely respond to a potential outbreak. This virus has been synthetized faster than any other in the past and is resulting in vaccines before most attenuated candidates reach clinical trials. Here, synthetic biology has the opportunity to demonstrate its truest potential to the public and solidify a footing in the world of vaccines.

[COVID-19 and vaccination: a global disruption]. / COVID-19 et vaccination : une dérégulation globale.

Coronavirus disease (COVID)-19 is an emerging pandemic infection whose significant ability to spread in a naïve population is well established. The first response of states to the COVID-19 outbreak was to impose lock-down and social barrier measures, such as wearing a surgical mask or social distancing. One of the consequences of this pandemic in terms of public health was the suspension or slowdown of infant vaccination campaigns, in almost all countries. The indirect effects of COVID-19 may therefore weigh on mortality from measles and polio in developing countries. In this pandemic chaos, the only hope lies in the rapid development of an effective vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). However, acceptance of this vaccine has not yet been won, as beyond the many unknowns that will inevitably weigh around such rapid development, skepticism among vaccine hesitants is growing.

TITLE: COVID-19 et vaccination : une dérégulation globale. ABSTRACT: La COVID-19 est une infection pandémique émergente dont l'importante capacité à se propager dans une population dénuée d'immunité n'est plus à prouver. La première réponse des États à la flambée de COVID-19 fut d'imposer un confinement et des mesures barrières, telles que le port du masque et la distanciation sociale. Une des répercussions de cette pandémie, en matière de santé publique, fut la suspension ou le ralentissement brusque des campagnes de vaccination des nourrissons, un peu partout dans le monde. Un des effets indirects de la COVID-19 est donc le risque de peser sur la mortalité mondiale, principalement via une recrudescence de la rougeole et de la poliomyélite, principalement dans les pays en voie de développement. Dans ce chaos potentiel, le seul espoir réside dans le développement rapide d'un vaccin efficace contre le SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2). Cependant, l'acceptation de ce vaccin par la population n'est pas évidente, car outre les nombreuses inconnues qui vont peser inévitablement dans le cas d'un développement très rapide du vaccin, le scepticisme des hésitants vaccinaux va à nouveau se développer.

[A race against the clock: creation of SARS-Cov-2 in the laboratory, a month after its emergence!] / Une course contre la montre - Création du SARS-CoV-2 en laboratoire, un mois après son émergence !

SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2, which emerged in China at the end of 2019, is responsible for a global health crisis resulting in the confinement of more than 3 billion people worldwide and the sharp decline of the world economy. In this context, a race against the clock is launched in order to develop a treatment to stop the pandemic as soon as possible. A study published in Nature by the Volker Thiel team reports the development of reverse genetics for SARS-CoV-2 allowing them to recreate the virus in just a few weeks. The perspectives of this work are very interesting since it will allow the genetic manipulation of the virus and thus the development of precious tools which will be useful to fight the infection. Even though this approach represents a technological leap that will improve our knowledge of the virus, it also carries the germ of possible misuse and the creation of the virus for malicious purposes. The advantages and disadvantages of recreating SARS-CoV-2 in this pandemic period are discussed in this mini-synthesis.

TITLE: Une course contre la montre - Création du SARS-CoV-2 en laboratoire, un mois après son émergence ! ABSTRACT: Le SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2), qui a émergé à la fin de l'année 2019 en République populaire de Chine, est responsable d'une crise sanitaire mondiale qui a entraîné le confinement de plus de 3 milliards d'individus et l'arrêt brutal de l'économie planétaire. Dans ce contexte, une course contre la montre est lancée afin de développer, dans les plus brefs délais, un traitement permettant d'enrayer la pandémie. Une étude de l'équipe de Volker Thiel, parue dans le journal Nature, rapporte la mise au point d'une technique de génétique inverse pour le SARS-CoV-2, leur ayant permis de recréer le virus en seulement quelques semaines. Les perspectives de ces travaux sont très intéressantes puisqu'elles permettent d'envisager la manipulation génétique du virus et ainsi le développement d'outils précieux qui seront utiles pour combattre l'infection. Si la technique représente également un saut technologique qui permettra d'améliorer nos connaissances sur le virus, elle porte aussi en elle le germe d'un possible mésusage et la création d'un virus à des fins malveillantes. Les avantages et inconvénients de recréer le SARS-CoV-2 dans cette période de pandémie sont discutés dans cet article.