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Updated: Apr 7, 2026

A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
Reducing the impact of influenza-associated secondary pneumococcal infections
Edin J Mifsud1, Amabel C Tan1, Kirsty R Short1
1Department of Microbiology and Immunology at the Peter Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia.
Abstract:
When administered prophylactically, we show that the Toll-like receptor-2 (TLR-2) agonist PEG-Pam2Cys (pegylated-S-(2,3-bis(palmitoyloxy)propyl)cysteine) not only mediates potent anti-viral activity against influenza virus but also reduces the impact of secondary infections with Streptococcus pneumoniae (the pneumococcus) by reducing (i) pulmonary viral and bacterial burdens, (ii) the levels of proinflammatory cytokines that normally accompany influenza and S. pneumoniae secondary infections and (iii) the vascular permeability of the pulmonary tract that can allow bacterial invasion of the blood in mice. We also show that an inactivated detergent-disrupted influenza virus vaccine formulated with the Pam2Cys-based adjuvant R4-Pam2Cys provides the host with both immediate and long-term protection against secondary pneumococcal infections following influenza virus infection through innate and specific immune mechanisms, respectively. Vaccinated animals generated influenza virus-specific immune responses that provided the host with long-term protection against influenza virus and its sequelae. This vaccine, which generates an immediate response, provides an additional countermeasure, which is ideal for use even in the midst of an influenza outbreak.
Insights
Toll-like receptor-2 (TLR-2) agonist PEG-Pam2Cys reduces influenza and secondary pneumococcal infections. A novel vaccine with R4-Pam2Cys adjuvant offers immediate and long-term protection against influenza and pneumococcus.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Influenza virus infections can lead to severe secondary bacterial pneumonia.
- Streptococcus pneumoniae (pneumococcus) is a common cause of secondary pneumonia post-influenza.
- Current treatments for secondary infections following influenza are limited.
Purpose of the Study:
- To investigate the prophylactic efficacy of a Toll-like receptor-2 (TLR-2) agonist against influenza and secondary pneumococcal infections.
- To evaluate a novel inactivated influenza virus vaccine formulated with a Pam2Cys-based adjuvant for protection against secondary pneumococcal infections.
Main Methods:
- Administration of PEG-Pam2Cys in a mouse model of influenza and secondary S. pneumoniae infection.
- Assessment of viral and bacterial burdens, cytokine levels, and vascular permeability.
- Vaccination with an inactivated influenza virus vaccine plus R4-Pam2Cys adjuvant followed by challenge with influenza and S. pneumoniae.
Main Results:
- PEG-Pam2Cys reduced pulmonary viral and bacterial loads, proinflammatory cytokines, and vascular permeability.
- The Pam2Cys-adjuvanted vaccine conferred immediate and long-term protection against secondary pneumococcal infections.
- Vaccinated mice exhibited robust influenza virus-specific immune responses.
Conclusions:
- TLR-2 agonists show promise in preventing severe outcomes of influenza and secondary bacterial infections.
- A novel inactivated influenza vaccine with a Pam2Cys adjuvant provides comprehensive protection against influenza and subsequent pneumococcal infections.
- This vaccine represents a valuable countermeasure, particularly during influenza outbreaks.
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