Identification of immunodominant CD8 epitope in the stalk domain of influenza B viral hemagglutinin.

Human infections by type B influenza virus constitute about 25% of all influenza cases. The viral hemagglutinin is comprised of two subunits, HA1 and HA2. While HA1 is constantly evolving in an unpredictable fashion, the HA2 subunit is highly conserved, making it a potential candidate for a universal vaccine. However, immunodominant epitopes in the HA2 subunit remain largely unknown. To delineate MHC Class I epitopes, we first identified 9-mer H-2Kd-restricted CD8 T cell epitopes in the HA2 domain by in silico analyses, followed by evaluating the immunodominance of these peptides in mice challenged with the virus. Of three peptides selected through in silico analysis, the universally conserved peptide, YYSTAASSL (B/HA2-190), possessed the highest predicted binding affinity to MHC Class I and was most effective in inducing IL-2 and TNF-α in mouse splenocytes. Importantly, the peptide demonstrated best capability of stimulating peptide-specific ex-vivo cytotoxicity against target cells. Taken together, this finding would be of value for assessment of cell-mediated immune responses elicited by vaccines based on the highly conserved HA2 stalk domain.

Responding to and managing multijurisdictional outbreaks of COVID-19 in Canadian industrial worksite/work camp settings.

SETTING: Early in the COVID-19 pandemic, the Public Health Agency of Canada (PHAC) and provincial/territorial (P/T) public health identified the need for a coordinated response to complex multijurisdictional COVID-19 outbreaks. The first large multijurisdictional industrial worksite COVID-19 outbreak highlighted the risk of transmission within these congregate work settings, the risk of transmission to the broader community(ies), and the need to develop setting-specific outbreak response frameworks. INTERVENTION: PHAC assembled a team to provide national outbreak support for multijurisdictional COVID-19 outbreaks in May 2020. The COVID-19 Outbreak Response Unit (ORU) worked with P/T partners to develop guiding principles for outbreak response and outbreak investigation processes, guidance documents, and investigation tools (e.g., minimum data elements and questionnaires). OUTCOMES: The ORU, P/T partners, and onsite industrial worksite health and safety staff leveraged outbreak investigation guidelines, industrial worksite outbreak process documents (including minimum data elements), and enhanced case questionnaires to respond to multiple COVID-19 outbreak investigations in industrial worksites. Clear roles/responsibilities and processes, along with standardized data, allowed for more efficient outbreak investigations and earlier implementation of mitigation measures. IMPLICATIONS: Multijurisdictional COVID-19 outbreaks highlighted the importance of public health collaboration with industry partners onsite. The assembly of a national outbreak response team was important to facilitate information sharing and provide technical support. Lessons learned and recommendations on outbreak preparation, detection, management, and communication are included to enhance a response framework applicable to future emerging or re-emerging pathogens with epidemic and/or pandemic potential.

RéSUMé: CONTEXTE: Au début de la pandémie de COVID-19, l'Agence de la santé publique du Canada (ASPC) et les autorités provinciales/territoriales de santé publique ont reconnu la nécessité d'une réponse coordonnée en cas d'éclosions complexes multi-juridictionnelles de COVID-19. La première grande éclosion multi-juridictionnelle de COVID-19 dans un chantier industriel a mis en évidence le risque de transmission dans ces milieux de travail collectifs, le risque de transmission à l'ensemble de la (des) communauté(s) et la nécessité d'élaborer des cadres d'intervention en cas d'éclosion spécifiques aux types de milieux. INTERVENTION: L'ASPC a formé une équipe chargée de soutenir la réponse nationale contre les éclosions multi-juridictionnelles de COVID-19 en mai 2020. L'Unité d'intervention en cas d'éclosion (UIE) de COVID-19 a collaboré avec des partenaires provinciaux et territoriaux pour élaborer des principes de référence pour la lutte contre les éclosions de COVID-19 et des processus d'enquête sur les éclosions, des documents d'orientation et des outils d'enquête (p.ex. des éléments de données minimales et des questionnaires). RéSULTATS: L'UIE, les provinces et territoires et le personnel chargé de la santé et sécurité du travail sur le site se sont appuyés sur des principes de référence aux enquêtes sur les éclosions, les documents de processus d'enquête sur les éclosions dans les sites industriels, y compris les éléments de données minimales et le questionnaire détaillé sur les cas, pour répondre à multiples enquêtes d'éclosions de COVID-19 dans les sites industriels. Des rôles/responsabilités et des processus clairs, ainsi que des données standardisées, ont permis de mener des enquêtes plus efficaces sur les éclosions et de mettre en œuvre plus rapidement des mesures d'atténuation. IMPLICATIONS: Les éclosions multi-juridictionnelles de COVID-19 ont mis en évidence l'importance de la collaboration entre les autorités de santé publique et les partenaires industriels sur site. La constitution d'une équipe nationale d'intervention en cas d'éclosion a été importante pour faciliter le partage des informations et fournir un soutien technique. Les connaissances acquises et les recommandations sur la préparation, la détection, la gestion et la communication des éclosions sont incluses afin d'améliorer le cadre de réponse aux futurs agents pathogènes émergents ou ré-émergents ayant un potentiel épidémique et/ou pandémique.

Bivalent vaccines effectively protect mice against influenza A and respiratory syncytial viruses.

Influenza and Respiratory Syncytial virus (RSV) infections together contribute significantly to the burden of acute lower respiratory tract infections. Despite the disease burden, no approved RSV vaccine is available. While approved vaccines are available for influenza, seasonal vaccination is required to maintain protection. In addition to both being respiratory viruses, they follow a common seasonality, which warrants the necessity for a concerted vaccination approach. Here, we designed bivalent vaccines by utilizing highly conserved sequences, targeting both influenza A and RSV, as either a chimeric antigen or individual antigens separated by a ribosome skipping sequence. These vaccines were found to be effective in protecting the animals from challenge by either virus, with mechanisms of protection being substantially interrogated in this communication.

Synthetic vaccine affords full protection to mice against lethal challenge of influenza B virus of both genetic lineages.

A quarter of all seasonal influenza cases are caused by type B influenza virus (IBV) that also dominates periodically. Here, we investigated a recombinant adenovirus vaccine carrying a synthetic HA2 representing the consensus sequence of all IBV hemagglutinins. The vaccine fully protected mice from lethal challenges by IBV of both genetic lineages, demonstrating its breadth of protection. The protection was not mediated by neutralizing antibodies but robust antibody-dependent cellular cytotoxicity and cell-mediated immune responses. Complete protection of the animals required the entire codon-optimized HA2 sequence that elicited a balanced immune response, whereas truncated vaccines without either the fusion peptide or the transmembrane domain reduced the efficacy of protection. Finally, the vaccines did not demonstrate any sign of disease exacerbation following lung pathology and morbidity monitoring. Collectively, these data suggest that it could be worth further exploring this prototype universal vaccine because of its considerable efficacy, safety, and breadth of protection.

Chlamydia trachomatis virulence factor CT135 is stable in vivo but highly polymorphic in vitro.

Chlamydia trachomatis is an important human pathogen causing both ocular and sexually transmitted disease. Recently, we identified CT135 as an important virulence determinant in a mouse infection model. Results from CEL 1 digestion assays and sequencing analyses indicated that CT135 was much more polymorphic in high in vitro passage reference serovars than it was in clinical strains that had undergone limited passaging. Herein, we used targeted next-generation sequencing of the CT134-135 locus, from reference strains and clinical isolates, enabling accurate discovery of single nucleotide polymorphisms and other population genetic variations. Our results indicate that CT134 is stable in all C. trachomatis serovars examined. In contrast, CT135 is highly polymorphic in high-passaged reference ocular and non-LGV genital serovars, with the majority of the mutations resulting in gene disruption. In low-passaged ocular clinical isolates, CT135 was frequently disrupted, whereas in genital clinical isolates CT135 was intact in almost all instances. When a serovar K isolate, with an intact CT134 and CT135, was subjected to serial passage in vitro CT134 remained invariable, while numerous gene interrupting mutations rapidly accumulated in CT135. Collectively, our data indicate that, for genital serovars, CT135 is under strong positive selection in vivo, and negative selection in vitro.