A 2-month field cohort study of SARS-CoV-2 in saliva of BNT162b2 vaccinated nursing home workers

peer reviewe

A Single Oral Immunization with Replication-Competent Adenovirus-Vectored Vaccine Induces a Neutralizing Antibody Response in Mice against Canine Distemper Virus.

peer reviewedCanine Distemper Virus (CDV) is a fatal and highly contagious pathogen of multiple carnivores. While injectable vaccines are very effective in protecting domestic animals, their use in the wild is unrealistic. Alternative vaccines are therefore needed. Adenovirus (AdV) vectors are popular vaccine vectors due to their capacity to elicit potent humoral and cellular immune responses against the antigens they carry. In parallel, vaccines based on live human AdV-4 and -7 have been used in U.S. army for several decades as replicative oral vaccines against respiratory infection with the same viruses. Based on these observations, the use of oral administration of replication competent AdV-vectored vaccines has emerged as a promising tool especially for wildlife vaccination. Developing this type of vaccine is not easy, however, given the high host specificity of AdVs and their very low replication in non-target species. To overcome this problem, the feasibility of this approach was tested using mouse adenovirus 1 (MAV-1) in mice as vaccine vectors. First, different vaccine vectors expressing the entire or part H or F proteins of CDV were constructed. These different strains were then used as oral vaccines in BALB/c mice and the immune response to CDV was evaluated. Only the strain expressing the full length CDV H protein generated a detectable and neutralizing immune response to CDV. Secondly, using this strain, we were able to show that although this type of vaccine is sensitive to pre-existing immunity to the vector, a second oral administration of the same vaccine is able to boost the immune response against CDV. Overall, this study demonstrates the feasibility of using replicating AdVs as oral vaccine vectors to immunize against CDV in wildlife carnivores

A Single Oral Immunization with a Replication-Competent Adenovirus-Vectored Vaccine Protects Mice from Influenza Respiratory Infection.

peer reviewedThe development of effective and flexible vaccine platforms is a major public health challenge, especially in the context of influenza vaccines that have to be renewed every year. Adenoviruses (AdVs) are easy to produce and have a good safety and efficacy profile when administered orally, as demonstrated by the long-term use of oral AdV-4 and -7 vaccines in the U.S. military. These viruses therefore appear to be the ideal backbone for the development of oral replicating vector vaccines. However, research into these vaccines is limited by the ineffectiveness of human AdV replication in laboratory animals. The use of mouse AdV type 1 (MAV-1) in its natural host allows infection to be studied under replicating conditions. Here, we orally vaccinated mice with a MAV-1 vector expressing influenza hemagglutinin (HA) to assess the protection conferred against an intranasal challenge of influenza. We showed that a single oral immunization with this vaccine generates influenza-specific and -neutralizing antibodies and completely protects mice against clinical signs and viral replication, similar to traditional inactivated vaccines. IMPORTANCE Given the constant threat of pandemics and the need for annual vaccination against influenza and possibly emerging agents such as SARS-CoV-2, new types of vaccines that are easier to administer and therefore more widely accepted are a critical public health need. Here, using a relevant animal model, we have shown that replicative oral AdV vaccine vectors can help make vaccination against major respiratory diseases more available, better accepted, and therefore more effective. These results could be of major importance in the coming years in the fight against seasonal or emerging respiratory diseases such as COVID-19

Oral vaccination with replication-competent adenovirus in mice reveals the dissemination of the viral vaccine beyond the gastrointestinal tract.

Since the 1970s, replication-competent human adenoviruses 4 and 7 have been used as oral vaccines to protect US soldiers against the severe respiratory diseases caused by these viruses. These vaccines are thought to establish a digestive tract infection conferring protection against respiratory challenge through antibodies. The success of these vaccines makes replication-competent adenoviruses attractive candidates for use as oral vaccine vectors. However, the inability of human adenoviruses to replicate efficiently in laboratory animals has hampered the study of such vectors. Here, we used mouse adenovirus type 1 (MAV-1) in mice to study oral replication-competent adenovirus-based vaccines. We showed that MAV-1 oral administration recapitulates the protection against homologous respiratory challenge observed with adenoviruses 4 and 7 vaccines. Moreover, live oral MAV-1 vaccine better protected against a respiratory challenge than inactivated vaccines. This protection was linked not only with the presence of MAV-1-specific antibodies but also with a better recruitment of effector CD8 T cells. However, unexpectedly, we found that such oral replication-competent vaccine systemically spread all over the body. Our results therefore support using MAV-1 to study replication-competent oral adenovirus-based vaccines but also highlight the fact that those vaccines could disseminate widely in the body.IMPORTANCE Replication-competent adenoviruses appear to be promising vectors for the development of oral vaccines in humans. However, study and development of these vaccines suffer from the lack of any reliable animal model. In this study, mouse adenovirus type 1 has been used to develop a small animal model for oral replication-competent adenovirus vaccines. While this model reproduced in mice what is observed with human adenovirus oral vaccines, it also highlighted that oral immunization with such replication-competent vaccine is associated with the systemic spread of the virus. This study is therefore of major importance for the future development of such vaccine platforms and their use in large human populations

Suppression of PPARβ, and DHA treatment, inhibit NaV1.5 and NHE-1 pro-invasive activities

International audienc

Caractérisation microbiologique de 3193 logements français des enfants de la cohorte ELFE

International audienc

Lipoprotein-associated phospholipase A2 during the hyperacute stage of ischemic and hemorrhagic strokes.

International audienceThe objectives of the study were to compare lipoprotein-associated phospholipase A2 (Lp-PLA2) levels in a prospective cohort including both ischemic and hemorrhagic strokes at the hyperacute phase, and to investigate if these levels were associated with stroke severity. Lp-PLA2 mass and activity were measured during the first 6 hours of symptom onset before any therapeutic intervention. The Lp-PLA2 level was analyzed by comparing the mass and activities in ischemic strokes and spontaneous intracerebral hemorrhages (ICH). Correlations between Lp-PLA2 levels and clinical scores as well as stroke volumes were made. The temporal evolution of Lp-PLA2 during the first week was analyzed in ischemic stroke patients. Lp-PLA2 mass was higher in ICH than in ischemic stroke (P = .001). Lp-PLA2 activity at admission correlated with initial and follow-up stroke volume in ICH (P = .003 and P = .004, respectively) but not in ischemic stroke. None of the measurements correlated with clinical severity for either diagnosis. Lp-PLA2 mass decreased during the first week after the use of statins in ischemic stroke, whereas the activity remained stable. Lp-PLA2 mass is higher in ICH compared with ischemic stroke during the hyperacute stage. Lp-PLA2 activity is associated with stroke volume in ICH but not in ischemic stroke. This suggests that Lp-PLA2 mass and activity could provide different information in the hyperacute stage of stroke

Ranolazine inhibits NaV1.5-mediated breast cancer cell invasiveness and lung colonization

International audienceBackground : NaV1.5 voltage-gated sodium channels are abnormally expressed in breast tumours and their expressionlevel is associated with metastatic occurrence and patients’death. In breast cancer cells, NaV1.5 activity promotes theproteolytic degradation of the extracellular matrix and enhances cell invasiveness.Findings : In this study, we showed that the extinction of NaV1.5 expression in human breast cancer cells almostcompletely abrogated lung colonisation in immunodepressed mice (NMRI nude). Furthermore, we demonstrated thatranolazine (50μM) inhibited NaV1.5 currents in breast cancer cells and reduced NaV1.5-related cancer cell invasivenessin vitro. In vivo, the injection of ranolazine (50 mg/kg/day) significantly reduced lung colonisation by NaV1.5-expressinghuman breast cancer cells.Conclusions : Taken together, our results demonstrate the importance of NaV1.5 in the metastatic colonisation oforgans by breast cancer cells and indicate that small molecules interfering with NaVactivity, such as ranolazine, mayrepresent powerful pharmacological tools to inhibit metastatic development and improve cancer treatments