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Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
Immunotherapy targeting the Streptococcus pyogenes M protein or streptolysin O to treat or prevent influenza A
Andrea L Herrera1, Christopher Van Hove1, Mary Hanson1
1Division of Basic Biomedical Sciences, The Sanford School of Medicine of the University of South Dakota, Vermillion, SD, United States of America.
Abstract:
Viral infections complicated by a bacterial infection are typically referred to as coinfections or superinfections. Streptococcus pyogenes, the group A streptococcus (GAS), is not the most common bacteria associated with influenza A virus (IAV) superinfections but did cause significant mortality during the 2009 influenza pandemic even though all isolates are susceptible to penicillin. One approach to improve the outcome of these infections is to use passive immunization targeting GAS. To test this idea, we assessed the efficacy of passive immunotherapy using antisera against either the streptococcal M protein or streptolysin O (SLO) in a murine model of IAV-GAS superinfection. Prophylactic treatment of mice with antiserum to either SLO or the M protein decreased morbidity compared to mice treated with non-immune sera; however, neither significantly decreased mortality. Therapeutic use of antisera to SLO decreased morbidity compared to mice treated with non-immune sera but neither antisera significantly reduced mortality. Overall, the results suggest that further development of antibodies targeting the M protein or SLO may be a useful adjunct in the treatment of invasive GAS diseases, including IAV-GAS superinfections, which may be particularly important during influenza pandemics.
Insights
Passive immunotherapy targeting Streptococcus pyogenes (group A streptococcus) showed potential in reducing illness during influenza A virus superinfections in mice. However, it did not significantly decrease mortality, suggesting further antibody development is needed.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Viral infections can be complicated by bacterial coinfections or superinfections.
- Group A Streptococcus (GAS) can cause severe outcomes, as seen during the 2009 influenza pandemic, despite penicillin susceptibility.
- Passive immunization is a potential strategy to enhance treatment outcomes for GAS infections.
Purpose of the Study:
- To evaluate the efficacy of passive immunotherapy targeting GAS in a murine model of influenza A virus (IAV)-GAS superinfection.
- To assess the effectiveness of antisera against streptococcal M protein and streptolysin O (SLO) in reducing morbidity and mortality.
Main Methods:
- A murine model of IAV-GAS superinfection was established.
- Mice received prophylactic or therapeutic administration of antisera targeting M protein or SLO.
- Outcomes were compared between treated groups and those receiving non-immune sera, focusing on morbidity and mortality.
Main Results:
- Prophylactic treatment with anti-M protein or anti-SLO antisera reduced morbidity but did not significantly decrease mortality.
- Therapeutic administration of anti-SLO antisera decreased morbidity, but neither antisera significantly reduced mortality.
- Morbidity was reduced in mice treated with immune sera compared to non-immune sera.
Conclusions:
- Antibodies targeting the M protein or SLO may serve as an adjunct therapy for invasive GAS diseases.
- This approach could be particularly beneficial for managing IAV-GAS superinfections, especially during influenza pandemics.
- Further development of these antibody-based therapies is warranted.
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