[mRNA vaccination, a model of transition from basic biology to medicine]. / Vaccination ARN messager (ARNm), modèle de transition de la biologie fondamentale à la médecine.

Sixty years elapsed between the discovery of messenger RNA (mRNA) and the use of this molecule in an unprecedented global vaccination campaign that brought the Covid-19 pandemic under control. Sixty years of doubts for some and certainties for others about the possibility of using mRNA-an example of synthetic biology-in therapeutic medicine and vaccinology. Years of "translational" research and development have culminated in the success of anti-Covid-19 mRNA vaccines and the promise of more to come against emerging pathogens. A new paradigm in vaccinology, enabling pandemics to be tackled as they emerge. A lesson to be learned: medical progress is less a question of time than of the critical nature of the biological discovery that underpins it. Before leaving us, François Gros, who played a key role in the discovery of mRNA, was able to appreciate the relevance of this obvious fact.

Soixante ans ont séparé la découverte de l'ARN messager (ARNm) et l'utilisation de cette molécule dans une campagne planétaire inédite de vaccination ayant permis le contrôle de la pandémie de Covid-19. Soixante ans de doutes chez certains et de certitudes chez d'autres sur la possibilité d'utiliser l'ARNm ­ un exemple de biologie de synthèse ­ en médecine thérapeutique et en vaccinologie. Des années de recherche et de développement «  translationnels  ¼ pour aboutir au succès de vaccins à ARNm anti-Covid-19 et à la promesse d'autres à venir contre de nouveaux pathogènes émergents. Un nouveau paradigme de la vaccinologie permettant d'attaquer les pandémies dans le temps de leur émergence. Une leçon à tirer, le progrès médical est moins affaire de temps que de la nature décisive de la découverte biologique qui le sous-tend. François Gros, acteur de la découverte de l'ARNm a pu, avant de nous quitter, juger de la pertinence de cette évidence.

The Future of Cancer Immunotherapy.

This article describes three emerging, novel cancer immunotherapies: BITE, TIL and cancer vaccines are therapies that recognize specific targets on cancer cells and trigger a specific immune response. So far, not all tumor types can benefit from these approaches the best results have been observed in hematological malignancies, melanoma, and lung cancer. These novel biological products are currently being tested in several cancer centers in Switzerland, and physicians must be familiar with these procedures, as some of their patients might be treated with such therapies in the near future.

[COVID-19 and adenovirus vaccines: French experience of enhanced pharmacovigilance]. / COVID-19 et vaccins à adénovirus : expérience française de suivi renforcé de pharmacovigilance.

As part of the COVID-19 vaccination campaign, the National Agency for the Safety of Medicines and Health Products and all 31 regional pharmacovigilance centers were mobilized in an exceptional reinforced vaccine pharmacovigilance surveillance system. Concerning adenovirus vaccines, Vaxzévria® and Jcovden®, this national system, based on the daily analysis of notified cases of adverse events, has allowed the early identification of safety signals, some of which have been validated, others still under analysis, common to mRNA vaccines or more specific of adenovirus vaccines such as Vaccine Induced Immune Thrombocytopenia. Complementing european and international actions, this follow-up has contributed to a better definition of the safety profile of these vaccines and has led to redefine the vaccine strategy in our country. Although today these two vaccines have no longer place in the national vaccine strategy, they are still used in other countries, where the experience acquired could be useful and will contribute to fuel the reflection on future therapies involving viral vectors.

Uncovering Public Perceptions of Older Adults' Vaccines in Canada: A Study of Online Discussions from National Media Sources.

This study explored how a subsection of Canadians perceive older adults' vaccines through a qualitative analysis of comments posted in response to national online news articles. We used reflexive thematic analysis to analyse 147 comments from 31 news article comments sections published between 2015 and 2020 from five different national online news sources (CBC, National Post, Global News, Globe & Mail, and Huffington Post Canada) that focused on three older adults' diseases and vaccines: influenza, pneumococcal pneumonia, and herpes-zoster. Three themes encompassed the similarities and differences in how these three diseases were discussed: (1) the importance of personal experiences on stated stance in vaccine uptake or refusal, (2) questioning vaccine research and recommendations, and (3) criticisms of the government's unequal vaccine opportunities across different Canadian provinces. Our findings identified that perceptions regarding older adult vaccination were dependent on the vaccine type, and, therefore, we make suggestions for future researchers to build on our findings, particularly the need not to treat the research subject of "older adults' vaccines" as one entity. Gaining a better understanding of how older adults' vaccines are perceived in Canada will enable public health professionals to develop effective communication strategies that should ultimately improve vaccination rates for older adults.

[Leptospirosis: A growing health threat to fish farming and recreational activities]. / La leptospirose : une menace sanitaire croissante pour les activités piscicoles et récréatives.

Leptospirosis is a cosmopolitan infectious disease caused by the bacteria Leptospirainterrogans, which is worldwide increasing as the result of climate changes favoring the reproduction of asymptomatic reservoir rodents and also flooding that brings mammals and humans into contact with contaminated water. This disease affects many mammals among wild, domestic or farmed animals. In humans, it is manifested through frustrated to severe forms that can lead to liver and kidney failure and death in about one in ten severe cases. Diagnostic methods and treatments are satisfactory. Prophylaxis is based on individual protective measures including vaccination. The single human vaccine that is available is expensive and it protects 97% against about a third of human pathogenic serovars. Moreover, this vaccine is not covered by health insurance. Better epidemiological knowledge, particularly at European level, could stimulate research in this area in order to obtain a vaccine that would protect more comprehensively against serovars pathogenic to humans.

Vaccinomics-driven proteome-wide screening of Haemophilus influenzae for the prediction of common putative vaccine candidates.

Haemophilus influenzae colonizes the respiratory tract and is associated with life-threatening invasive infections. The recent rise in its global prevalence, even in the presence of multiple vaccines, indicates an urgent need to develop effective cross-strain vaccine strategies. Our work focused on identifying the universally conserved antigenic regions of H. influenzae that can be used to develop new vaccines. A variety of bioinformatics tools were applied for the comprehensive geno-proteomic analysis of H. influenzae type a strain, as reference serotype, through which subcellular localization, essentiality, virulence, and non-host homology were determined. B and T cell epitope mapping of the 3D protein structures were performed. Thereafter, molecular docking with HLA_DRB1*0101 and comparative genome analysis established the candidature of the identified regions. Based on the established vaccinomics criteria, five target proteins were predicted as novel vaccine candidates. Among these, nine epitopic regions that could regulate lymphocyte activity through strong protein-protein interactions were identified. Comparative genomic analysis revealed that the identified regions were highly conserved among the different strains of H. influenzae. Based on multiple immunogenic factors, five prioritized proteins and their predicted epitopes were identified as ideal common putative vaccine candidates against typeable strains.

"Imagine the Perfect Vaccine": Homeopathic Vaccine Alternatives and Vaccine Discourse in English Canada.

Advocates of homeopathic vaccines, also known as nosodes, reimagined the risks and benefits of vaccination from 1999 to 2015 by comparing "risky" vaccines to "risk-free" nosodes. I argue that nosodes allowed for a complementary argument to anti-vaccine discourse, fundamentally altering what had been framed as a choice between the risks of vaccination and the risks of vaccine-preventable disease. Despite evidence of their efficacy being flawed, advocates presented nosodes as an alternative to vaccines and a middle ground between anti-vaccination and vaccination. While a campaign from 2013 to 2015 tried to expose nosodes as ineffective, I argue that the campaign was unsuccessful. Instead, the mainstream media brought more attention to nosodes. The history of nosodes further complicates the history of vaccines and alternative medicine in Canada by adding vaccine alternatives to the growing literature on vaccine hesitancy.

COVID-19 pathophysiology and pharmacology: what do we know and how did Canadians respond? A review of Health Canada authorized clinical vaccine and drug trials.

Coronavirus disease 2019 (COVID-19) has resulted in the death of over 18 000 Canadians and has impacted the lives of all Canadians. Many Canadian research groups have expanded their research programs to include COVID-19. Over the past year, our knowledge of this novel disease has grown and has led to the initiation of a number of clinical vaccine and drug trials for the prevention and treatment of COVID-19. Here, we review SARS-CoV-2 (the coronavirus that causes COVID-19) and the natural history of COVID-19, including a timeline of disease progression after SARS-CoV-2 exposure. We also review the pathophysiological effects of COVID-19 on the organ systems that have been implicated in the disease, including the lungs, upper respiratory tract, immune system, central nervous system, cardiovascular system, gastrointestinal organs, the liver, and the kidneys. Then we review general therapeutics strategies that are being applied and investigated for the prevention or treatment of COVID-19, including vaccines, antivirals, immune system enhancers, pulmonary supportive agents, immunosuppressants and (or) anti-inflammatories, and cardiovascular system regulators. Finally, we provide an overview of all current Health Canada authorized clinical drug and vaccine trials for the prevention or treatment of COVID-19.

[How to improve vaccination coverage in France? Qualitative study among health care workers]. / Comment améliorer la couverture vaccinale en France ? Étude qualitative auprès de professionnels de santé.

BACKGROUND: The risk benefit ratio has been clearly proven for a long time to be in favor of vaccination. However, the vaccine distrust is still increasing in the French population and vaccination coverage could be improved. There is a real need to increase confidence in vaccination. In this study, we interviewed heath care workers to collect their opinion concerning vaccination hesitancy amongst their patients. METHODS: A qualitative study, using semi structured interviews, was performed. All the Pharmacists and doctors were interviewed by the same person using an interview guide prepared by a multidisciplinary team. Interviews were recorded and transcribed verbatim, then used as a basis for analysis and synthesis of the areas where improvement seems possible for the health care workers interviewed. RESULTS: Data saturation was obtained after 10 interviews. Analysis of the verbatim allowed the classification of the leads proposed by health care workers in three main themes: improvement of transparency and restoration of the trust for vaccine policy, improved initial and further training of health care workers, and a better communication towards the population. CONCLUSION: Results provide helpful insights into practical avenues to improve the vaccination confidence. If some of them need an in-depth reflection, others could be easily implemented in order to increase the adhesion of the population to vaccination, and consequently the vaccination coverage.

Frontrunners in the race to develop a SARS-CoV-2 vaccine.

Numerous studies continue to be published on the COVID-19 pandemic that is being caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Given the rapidly evolving global response to SARS-CoV-2, here we primarily review the leading COVID-19 vaccine strategies that are currently in Phase III clinical trials. Nonreplicating viral vector strategies, inactivated virus, recombinant protein subunit vaccines, and nucleic acid vaccine platforms are all being pursued in an effort to combat the infection. Preclinical and clinal trial results of these efforts are examined as well as the characteristics of each vaccine strategy from the humoral and cellular immune responses they stimulate, effects of any adjuvants used, and the potential risks associated with immunization such as antibody-dependent enhancement. A number of promising advancements have been made toward the development of multiple vaccine candidates. Preliminary data now emerging from phase III clinical trials show encouraging results for the protective efficacy and safety of at least 3 frontrunning candidates. There is hope that one or more will emerge as potent weapons to protect against SARS-CoV-2.

COVID-19 basics and vaccine development with a Canadian perspective.

The ongoing coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving situation. New discoveries about COVID-19 and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to deepen the understanding of this novel disease. As there is currently no COVID-19 specific treatment, isolation is the most effective method to prevent transmission. Moreover, development of a safe and effective COVID-19 vaccine will be instrumental in reinstating pre-COVID-19 conditions. As of 31 July 2020, there are at least 139 vaccine candidates from around the globe in preclinical evaluation, with another 26 undergoing clinical evaluation. This paper aims to review the basics of COVID-19, including epidemiology, basic biology of SARS-CoV-2, and transmission. We also review COVID-19 vaccine development, including animal models, platforms under development, and vaccine development in Canada.

[Vaccine recommendations for children with idiopathic nephrotic syndrome]. / Recommandations vaccinales pour les enfants avec un syndrome néphrotique idiopathique.

The specific treatment of idiopathic nephrotic syndrome is based on corticosteroid therapy and/or steroid-sparing immunosuppressive agents in children who are steroid-dependant or frequent relapsers (60-70 %). Patients have an increased infectious risk not only related to the disease during relapses (hypogammaglobulinemia and urinary leakage of opsonins) but also to treatments (corticosteroids or immunosuppressive agents) in period of remission. Vaccination is therefore particularly recommended in these patients. Potential vaccine risks are ineffectiveness, induction of vaccine disease and relapse of idiopathic nephrotic syndrome. Only live vaccines expose to the risk of vaccine disease: they are in general contra-indicated under immunosuppressive treatment. The immunogenicity of inactivated vaccines is reduced but persists. The immunogenic stimulus of vaccination may in theory trigger a relapse of the nephrotic syndrome. Nevertheless, this risk is low in the literature, and even absent in some studies. The benefit-risk ratio is therefore in favor of vaccination with respect to the vaccination schedule for inactivated vaccines, with wide vaccination against pneumococcus and influenza annually. Depending on the context and after expert advice, immunization with live vaccines could be discussed if residual doses/levels of immunosuppressive treatments are moderate and immunity preserved.

Influence of information sources on vaccine hesitancy and practices.

INTRODUCTION: Many factors influence vaccination practices and attitudes. This study aimed to identify vaccine information sources used by parents of children aged 1-15 years to get a better understanding of the relation between vaccine information sources, practices for two vaccines (MMR, HBV), vaccine acceptance, and vaccine hesitancy. METHODS: A total of 3938 parents, drawn by random sampling, were interviewed by telephone as part of the "2016 health barometer" survey. Vaccine information sources were described and analyzed according to socio-demographic variables. Multivariate logistic regression models were then built to explain vaccine information sources usage, vaccination practices and attitudes. RESULTS: Healthcare professionals (HCP), the Internet, and relatives were the three main vaccine information sources. Vaccination practices and acceptance were better when parents were getting information from HCPs compared with parents getting information from the Internet or relatives. Besides, getting information from the three different types of sources was associated with the highest rate of vaccine hesitancy: 70.9% (OR=4.6; P<0.0001) versus 34.6% among parents getting information from HCPs only. CONCLUSION: Those results suggest an interest in providing quality information about vaccination on the Internet. The primary role of HCPs in vaccination decision is once again demonstrated.

[Preventing cancer: The role of Papillomavirus vaccination in the general population]. / Prévenir les cancers : place de la vaccination Papillomavirus en population générale.

Papillomavirus (HPV), the first sexually transmitted disease in the world, is the main infectious agent responsible for cancer (6300 per year, in France). The cycle of HPV infection - >precancerous lesions - >cancer is well documented with regard to the cervix (cf. Nobel Prize in 2008). While this area is the most frequent (3000), it is far from being the only one. Other cancers include the anus, oropharyngeal sphere, glans and vulva. The sum of these other induced HPV cancers is greater than the total number of cervical cancers and also concerns boys. Screening is essential but insufficient and only concerns the cervix. Only vaccination can provide primary and general prevention. Since 2007, there have been many studies demonstrating its excellent efficacy and tolerance. However, France lags behind other countries with a vaccination coverage (<30 %) that does not allow for an epidemiological impact.

Aluminum and vaccines: Current state of knowledge.

French people have never been so wary about vaccines. The use of aluminum salts in vaccine adjuvants to enhance effectiveness is one of the major reasons for this lack of confidence. The direct toxicity of aluminum is often put forward. Direct toxicity of aluminum has long been known-especially with occupational exposure-to be associated with characteristic clinical manifestations and increased blood aluminum level. Intoxication related to the excessive amount of an element in the body, whether be it lead poisoning following exposure to lead or mercury poisoning for instance, is always associated with metal increase in biological media. To date no link has been established between the direct toxicity of aluminum and vaccines. Aluminum levels in biological media of vaccinated subjects are not different from those of unvaccinated subjects. This is consistent with the very small amount of aluminum contained in one dose of vaccine. Indirect toxicity of aluminum was suggested to explain macrophagic myofasciitis in humans in 2011, a disease that could be mediated by an autoimmune/autoinflammatory mechanism. This hypothesis has recently been refuted in a large pharmaco-epidemiological study proving that aluminum-containing adjuvants of vaccines are not responsible for this autoimmune/autoinflammatory syndrome.

Experimental infections in humans-historical and ethical reflections.

Vaccine efficacy and prophylactic treatment of infections are tested best when the vaccinated or treated individual is challenged through deliberate infection with the respective pathogen. However, this trial design calls for particular ethical caution. Awareness of the history of challenge trials is indispensable, including trials that were problematic or even connected to abuse. We briefly introduce historical aspects of experimental infections in humans and the ethical debate around them and give estimates of the numbers of volunteers participating in human experimental infection models. Challenge models can offer a great chance and benefit for the development of medical interventions to fight infectious diseases, but only when they are appropriately controlled and regulated.

L'efficacité des vaccins et le traitement prophylactique des infections sont mieux testés lorsque l'individu vacciné ou traité est exposé par le biais d'une infection délibérée par l'agent pathogène concerné. Cependant, cette conception d'essai appelle à une prudence éthique particulière. Il est indispensable de connaître l'histoire des essais cliniques, y compris des essais qui se sont avérés problématiques ou même liés à des abus. Nous présentons brièvement les aspects historiques des infections expérimentales chez l'homme et le débat éthique autour d'eux et donnons des estimations du nombre de volontaires participant à des modèles d'infection expérimentale humaine. Les modèles d'exposition peuvent offrir une grande chance et un avantage pour le développement d'interventions médicales pour lutter contre les maladies infectieuses, mais uniquement lorsqu'elles sont contrôlées et réglementées de manière appropriée.

[Alterations in responses to vaccines in older people]. / Altération des réponses vaccinales avec l'âge.

The aging population raises a number of public health issues including a need to address the severity and frequency of infections observed in older people. Vaccines play an important role in prevention. However, immunosenescence alters the intensity and quality of vaccine responses, thus limiting the impact of recommendations directed after 65 years for vaccination against flu, pneumococci, pertussis, tetanus and zoster. Immunosenescence, aggravated by co-morbidities, varies with age, becoming apparent after 60-65 years and more profound after 85 years. All stages of vaccine responses are affected by immunosenescence, from the innate immunity required to activate these responses to the induction of protective antibody responses and immune memory. Nevertheless, the capacity to develop new responses to primary vaccination is more affected than the ability to respond to recalls, although this is also impaired. Responses to vaccines are differentially altered depending on vaccine and age. Influenza vaccines are modestly immunogenic and several meta-analyses agree an estimate for efficacy of about 50% against virologically-proven flu and 40% against flu-related deaths. The anti-pneumococcal 23-valent non-conjugated vaccine does not induce memory while the 13-valent conjugated one does, but their efficacy are likely to be similar between 70 to 52% before 75 years. A sequential vaccination program with the 13-valent primo-vaccination followed by the 23-valent, recommended in immune-suppressed patients, is currently being studied in France. The waning of immunity to pertussis makes recalls necessary in the elderly who develop good antibody responses. Several research avenues are currently being pursued to try improve the degree of protection conferred by these vaccines in elderly.

Clinical trials in low-resource settings: the perspectives of caregivers of paediatric participants from Uganda, Tanzania and Kenya.

OBJECTIVES: Vaccine clinical trials in low-resource settings have unique challenges due to structural and financial inequities. Specifically, protecting participant and caregiver autonomy to participate in the research study can be a major challenge, so understanding the setting and contextual factors which influence the decision process is necessary. This study investigates the experience of caregivers consenting on behalf of paediatric participants in a malaria vaccine clinical trial where participation enables access to free, high-quality medical care. METHODS: We interviewed a total of 78 caregivers of paediatric participants previously enrolled in a phase II or III malaria vaccine clinical trial in Uganda, Tanzania and Kenya. Interviews were qualitative and analysed using a thematic framework analysis focusing on the embodied caregiver in the political, economic and social reality. RESULTS: Caregivers of participants in this study made the decision to enrol their child based on economic, social and political factors that extended beyond the trial into the community and the home. The provision of health care was the dominant reason for participation. Respondents reported how social networks, rumours, hierarchal structures, financial constraints and family dynamics affected their experience with research. CONCLUSIONS: The provision of medical care was a powerful motivator for participation. Caregiver choice was limited by structural constraints and scarce financial resources. The decision to participate in research extended beyond individual consent and was embedded in community and domestic hierarchies. Future research should assess other contexts to determine how the choice to participate in research is affected when free medical care is offered.

OBJECTIFS: Les essais cliniques de vaccins dans les régions à faibles ressources présentent des défis uniques en raison d'iniquités structurelles et financières. En particulier, la protection de l'autonomie des participants et des soignants dans la participation à l'étude de recherche peut être un défi majeur. Il est donc nécessaire de comprendre le contexte et les facteurs contextuels qui influencent le processus de décision. Cette étude examine l'expérience de soignants consentants au nom de participants pédiatriques à un essai clinique de vaccin antipaludique où la participation permet l'accès à des soins médicaux gratuits et de haute qualité. MÉTHODES: Nous avons interviewé un total de 78 soignants de participants pédiatriques qui avaient participé à un essai clinique de vaccin antipaludique de phase II ou III en Ouganda, en Tanzanie et au Kenya. Les entretiens ont été qualitatifs et analysés à l'aide d'une analyse de cadre thématique centrée sur le soignant, en tenant compte de la réalité politique, économique et sociale. RÉSULTATS: Les soignants des participants à cette étude ont pris la décision d'inscrire leur enfant sur base de facteurs économiques, sociaux et politiques qui s'étendaient au-delà de l'essai dans la communauté et à la maison. La fourniture de soins de santé était la principale raison de la participation. Les répondants ont rapporté comment les réseaux sociaux, les rumeurs, les structures hiérarchiques, les contraintes financières et la dynamique familiale ont affecté leur expérience avec la recherche. CONCLUSIONS: La fourniture de soins médicaux était un puissant facteur de motivation pour la participation. Le choix du soignant était limité par des contraintes structurelles et les ressources financières limitées. La décision de participer à la recherche allait au-delà du consentement individuel et s'inscrivait dans les hiérarchies communautaires et domestiques. Les recherches futures devraient évaluer d'autres contextes afin de déterminer comment le choix de participer à la recherche est affecté par la gratuité des soins médicaux.