mBio
Department of Microbiology and Immunology, The University of Melbourne, at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan.
Published: October 2015
Unlabelled: The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity.
Importance: The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of exposure to infectious agents, while adaptive immunity takes several days to become effective. Here we show, by using a simple lipopeptide-based TLR2 agonist, that an influenza detergent-split vaccine can be made to simultaneously stimulate and amplify both systems to provide immediate antiviral protection while giving the adaptive immune system time to implement long-term immunity. Both types of immunity induced by this approach protect against vaccine-matched as well as unrelated virus strains and potentially even against strains yet to be encountered. Conferring dual functionality to influenza vaccines is beneficial for improving community protection, particularly during periods between the onset of an outbreak and the time when a vaccine becomes available or in scenarios in which mass vaccination with a strain to which the population is immunologically naive is imperative.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626850 | PMC |
http://dx.doi.org/10.1128/mBio.01024-15 | DOI Listing |
J Paediatr Child Health
January 2025
WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, Doherty Institute, Melbourne, Victoria, Australia.
Aims: Primary aim was to review severe acute respiratory infections (SARI) hospitalisations caused by respiratory syncytial virus (RSV) in children aged < 2 years in paediatric hospitals in Australia. Secondary aims included RSV subtyping, assessing RSV seasonality and contributing to the World Health Organisation's RSV surveillance programme.
Methods: We prospectively reviewed the medical records of children (< 2 years of age) with a confirmed SARI who were admitted to one of four major Australian paediatric hospitals and had a respiratory sample analysed by Polymerase Chain Reaction (PCR).
BMC Health Serv Res
January 2025
University of California, San Francisco Institute for Health & Aging, #123K, 490 Illinois Street, San Francisco, CA, 94158, USA.
Background: Mobile Health Clinics (MHCs) are an alternate form of healthcare delivery that may ameliorate current rural-urban health disparities in chronic diseases and have downstream impacts on the health system by reducing costs. Evaluations of providers' time allocation on MHCs are scarce, hindering knowledge transfer related to MHC implementation strategies.
Methods: Retrospective economic cost was assessed using business ledgers and expert assessments in 2023 US Dollar (USD) from 2022 to 2023.
BJGP Open
January 2025
Department of Family Medicine & Population Health, Belgium, University of Antwerp, Antwerp.
Background: Illness severity, comorbidity, fever, age and symptom duration influence antibiotic prescribing for respiratory tract infections (RTI). Non-medical determinants, such as patient expectations, also impact prescribing.
Aim: To quantify the effect of general practitioners' (GPs') perception of a patient request for antibiotics on antibiotic prescribing for RTI and investigate effect modification by medical determinants and country.
Biologicals
January 2025
Centre for Human Drug Research (CHDR), Leiden, the Netherlands; Leiden University Medical Center (LUMC), Leiden, the Netherlands.
Inno4Vac, a public-private partnership funded by the IMI2/EU/EFPIA Joint Undertaking (IMI2 JU), brings together academic institutions, SMEs, and pharmaceutical companies to accelerate and de-risk vaccine development. The project has made significant strides in the selection and production of challenge agents for influenza, respiratory syncytial virus (RSV), and toxigenic Clostridioides difficile for controlled human infection model studies (CHIMs). A regulatory workshop held on March 20, 2024, addressed the standardisation of clinical procedures, ethical considerations, endpoints, and data integrity, highlighting the ongoing initiatives related to these CHIMs.
View Article and Find Full Text PDFVaccine
January 2025
Department of Immunology and Microbial Disease, Albany Medical College, 47 New Scotland Ave, Albany, NY 12208, United States.
The development of safe and effective mucosal vaccines are hampered by safety concerns associated with adjuvants or live attenuated microbes. We previously demonstrated that targeting antigens to the human-Fc-gamma-receptor-I (hFcγRI) eliminates the need for adjuvants, thereby mitigating safety concerns associated with the mucosal delivery of adjuvant formulated vaccines. Here we evaluated the role of the route of immunization in the mucosal immunity elicited by the hFcγRI-targeted vaccine approach.
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