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

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.

Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection

“…Our findings are consistent with data from other forms of streptococcus vaccines that overcome influenza virus‐mediated defects in host immune responses 2,42 . Immunity against streptococcus is an important component of protection against influenza virus : streptococcus super‐infection, 2 ultimately protecting against secondary bacterial complications.…”

“…Streptococcal super‐infection following influenza A virus infection is a major concern. Over a quarter of fatalities reported in one study because of bacterial super‐infections in influenza patients were caused by streptococcus, 42 while in another study, 7 of 10 patients with a streptococcal super‐infection died 43 . Those who died had a median age of 37 years.…”

“…Our findings are consistent with data from other forms of streptococcus vaccines that overcome influenza virus‐mediated defects in host immune responses. 2 , 42 Immunity against streptococcus is an important component of protection against influenza virus : streptococcus super‐infection, 2 ultimately protecting against secondary bacterial complications. However, we provide the first report of a vaccine against a super‐infection using conserved protective epitopes from both pathogens formulated within the same liposome.…”

Secondary streptococcal infection following influenza

“…M protein, one of the cell‐surface proteins of S. pyogenes , was reported to be another IAV– S. pyogenes co‐infection contributor 90 . Immunization against the M protein or passive immunotherapy using anti–M protein antiserum has been shown to prevent death of mice with IAV– S. pyogenes co‐infection 97,98 . In addition, the fibronectin/tenascin‐binding protein PrtF.2 of S. pyogenes is reported to contribute to IAV co‐infection virulence 99 …”

“…90 Immunization against the M protein or passive immunotherapy using anti-M protein antiserum has been shown to prevent death of mice with IAV-S. pyogenes co-infection. 97,98 In addition, the fibronectin/tenascin-binding protein PrtF.2 of S. pyogenes is reported to contribute to IAV co-infection virulence. 99 IAV-infected cells have been found to produce various cytokines and chemokines.…”