Immunotherapy targeting the Streptococcus pyogenes M protein or streptolysin O to treat or prevent influenza A superinfection.

Andrea L Herrera,Rodney K Tweten,Michael S Chaussee,Mary Hanson,James B Dale,Victor C Huber,Diego Diel,Christopher Van Hove,Jens Kreth

doi:10.1371/journal.pone.0235139

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.

Highlights

Infection with influenza A virus (IAV) creates a permissive environment for secondary bacterial infections, which significantly increases the morbidity and mortality associated with both IAV epidemics and pandemics [1]
To prepare stocks to inoculate mice, group A streptococcus (GAS) was grown overnight with THY agar, colonies were inoculated into pre-warmed THY medium, Immunotherapy to treat or prevent influenza A superinfection grown to the mid-exponential phase of growth (A600 = 0.5), and diluted in sterile phosphatebuffered saline (PBS; pH 7.4)
The titers of antigen-specific antibodies against the streptolysin O (SLO) or the M protein vaccines were determined by using an enzyme-linked immunosorbent assay (ELISA) and were 600,000 and 400,000 respectively (Fig 1)

Summary

Introduction

Infection with influenza A virus (IAV) creates a permissive environment for secondary bacterial infections (often referred to as superinfections), which significantly increases the morbidity and mortality associated with both IAV epidemics and pandemics [1]. Immunotherapy to treat or prevent influenza A superinfection group A streptococcal vaccines. The technology has been licensed from the University of Tennessee Research Foundation to Vaxent, LLC. Dr Dale is the Chief Scientific Officer of Vaxent and is a member. Additional patents related to other similar vaccines have since been submitted or have issued in the US, Europe, and elsewhere. This does not alter our adherence to PLOS ONE policies on sharing data and materials without restrictions

Methods

Results

Conclusion