Vaccine-Induced Th1-Type Response Protects against Invasive Group A Streptococcus Infection in the Absence of Opsonizing Antibodies

Abstract

Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-␥), and tumor necrosis alpha (TNF-␣) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy. Citation Rivera-Hernandez T, Rhyme MS, Cork AJ, Jones S, Segui-Perez C, Brunner L, Richter J, Petrovsky N, Lawrenz M, Goldblatt D, Collin N, Walker MJ. 2020. Vaccine-induced Th1-type response protects against invasive group A Streptococcus infection in the absence of opsonizing antibodies. mBio 11:e00122-20.

A Review of Streptococcus pyogenes: Public Health Risk Factors, Prevention and Control

“…Other prevention and control measures include improving the quality of housing [ 15 , 20 ], improved hand hygiene practices [ 15 , 42 ] and the reduction of overcrowding [ 15 ]. Other proposed methods to reduce GAS transmission that are not currently used include vaccination [ 89 , 102 , 107 , 108 , 109 , 110 ] and screening for GAS during pregnancy [ 41 , 63 , 67 , 97 , 119 ].…”

“…This process has been hindered by factors like the availability of various unique GAS serotypes, antigenic variations within the same serotype, safety concerns, and a lack of consensus on clinical endpoints for the establishment of proof of concept [ 108 , 110 , 147 , 148 ]. Studies in this review, however, indicate that vaccination could help reduce these diseases, and therefore highly recommend its development and use [ 89 , 102 , 107 , 108 , 109 , 110 ]. Rivera-Hernandez et al [ 109 ] suggest that vaccination can reduce antibiotic use and therefore reduce antibiotic resistance.…”

“…Studies in this review, however, indicate that vaccination could help reduce these diseases, and therefore highly recommend its development and use [ 89 , 102 , 107 , 108 , 109 , 110 ]. Rivera-Hernandez et al [ 109 ] suggest that vaccination can reduce antibiotic use and therefore reduce antibiotic resistance. Reducing antibiotic resistance will further reduce the transmission of GAS infections through increased treatment success, as discussed earlier.…”

M-protein based vaccine induces immunogenicity and protection from Streptococcus pyogenes when delivered on a high-density microarray patch (HD-MAP)

“…In this study, J8-DT/HD-MAP vaccination induced antibodies that are characteristic of the Th1 type responses and as such could lead to cellular responses capable of targeting S. pyogenes. Moreover, Th1 immune responses have been shown to promote protection against systemic invasive S. pyogenes infection 56 .…”

Immunogenicity Assessment of Different Segments and Domains of Group A Streptococcal C5a Peptidase and Their Application Potential as Carrier Protein for Glycoconjugate Vaccine Development

“…Further studies in children have indicated that ScpA was highly immunogenic in human and the elicited antibodies could neutralize the activity of natural ScpA [ 34 ]. More recently, ScpA has been also used as one antigenic component for combination vaccines, whose immunities were well identified in a nonhuman primate model or a humanized plasminogen AlbPLG1 mice model [ 35 , 36 , 37 , 38 ]. In our previous study, we demonstrated that an enzymatically inactive ScpA mutant (His193Ala mutation, ScpA193) provoked robust T cell-mediated immune responses featured by the production of high titers of ScpA-specific IgG antibodies [ 39 ].…”