Clin Exp Vaccine Res.  2017 Jan;6(1):45-49. 10.7774/cevr.2017.6.1.45.

Trivalent M-related protein as a component of next generation group A streptococcal vaccines

• Courtney H
• Niedermeyer SE
• Penfound T
• Hohn CM
• Greeley A
• Dale JB

• KMID: 2366891
• DOI: http://doi.org/10.7774/cevr.2017.6.1.45

Abstract

PURPOSE
There is a need to broaden protective coverage of M protein-based vaccines against group A streptococci (GAS) because coverage of the current 30-valent M protein vaccine does not extend to all emm types. An additional GAS antigen and virulence factor that could potentially extend vaccine coverage is M-related protein (Mrp). Previous work indicated that there are three structurally related families of Mrp (MrpI, MrpII, and MrpIII) and peptides of all three elicited bactericidal antibodies against multiple emm types. The purpose of this study was to determine if a recombinant form containing Mrp from the three families would evoke bactericidal antiserum and to determine if this antiserum could enhance the effectiveness of antisera to the 30-valent M protein vaccine.
MATERIALS AND METHODS
A trivalent recombinant Mrp (trMrp) protein containing N-terminal fragments from the three families (trMrp) was constructed, purified and used to immunize rabbits. Anti-trMrp sera contained high titers of antibodies against the trMrp immunogen and recombinant forms representing MrpI, MrpII, and MrpIII.
RESULTS
The antisera opsonized emm types of GAS representing each Mrp family and also opsonized emm types not covered by the 30-valent M protein-based vaccine. Importantly, a combination of trMrp and 30-valent M protein antiserum resulted in higher levels of opsonization of GAS than either antiserum alone.
CONCLUSION
These findings suggest that trMrp may be an effective addition to future constructs of GAS vaccines.

Keyword

Streptococcus pyogenes; Vaccines; Virulence factors

MeSH Terms

Antibodies
Humans
Immune Sera
Peptides
Rabbits
Staphylococcal Protein A*
Streptococcal Vaccines*
Streptococcus pyogenes
Vaccines
Virulence
Virulence Factors
Antibodies
Immune Sera
Peptides
Staphylococcal Protein A
Streptococcal Vaccines
Vaccines
Virulence Factors

Figure

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  Fig. 1 Schematic of the trivalent recombinant M-related protein (Mrp) vaccine construct. Mrps comprise three structurally related families: MrpI (represented by Mrp2), MrpII (represented by Mrp4), and MrpIII (represented by Mrp49).

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  Fig. 2 Bactericidal activity of trivalent M-related protein (Mrp) vaccine rabbit antisera against multiple group A streptococci (GAS) emm types expressing Mrp from the three Mrp families, Mrp I-III. M5 GAS does not express Mrp and served as a negative control. Bars represent the mean±standard error of mean of four independent experiments.

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  Fig. 3 Combinations of 30-valent M protein and trivalent M-related protein (Mrp) (trMrp) antisera promote enhanced bactericidal killing against multiple Mrp-positive group A streptococci (GAS) emm types. Antisera to trMrp (blue column) or to 30-valent M protein vaccine (orange column) were used alone or in combination with each other (red column). Antisera were mixed with an equal volume of normal rabbit serum when used singly and equal volumes of each when combined. Bars represent the mean±standard error of mean of four independent experiments. The asterisk above the bars indicates that the combination of anti-trMrp and anti-30-valent sera was significantly different in killing (p<0.05) than either antisera alone.

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