Thesis Format
Monograph
Degree
Master of Science
Program
Microbiology and Immunology
Supervisor
McCormick, John K.
Abstract
Streptococcus pyogenes is a Gram-positive, human-specific pathogen that colonizes the skin and upper respiratory tract, causing various invasive diseases including bacteremia and toxic shock syndrome. The M protein, a prominent virulence factor that enables resistance to phagocytosis and complement-mediated killing, represents an attractive vaccine target. This study investigated whether intranasal immunization with recombinant M proteins from serotypes M12, M3, and M18—with or without alum adjuvant—could protect transgenic B6HLA mice from nasopharyngeal challenge. Despite modest increases in serum IgG titers, particularly for full-length and conserved-region M12 constructs and M3 with alum, none of these formulations significantly reduced S. pyogenes burden. Robust mucosal IgA responses were not induced in most vaccination groups, and even those with detectable IgA did not improve opsonophagocytic clearance in vitro. Our findings highlight the challenges of eliciting strong mucosal immunity against S. pyogenes using M protein constructs with alum, suggesting future work should explore alternative adjuvants, delivery routes, or prime-boost strategies.
Summary for Lay Audience
Streptococcus pyogenes is a globally prevalent bacterium capable of causing infections ranging from common “strep throat” to serious illnesses like streptococcal toxic shock syndrome. Research has historically focused on the M protein—a major surface molecule of S. pyogenes—as a promising vaccine target, primarily because it blocks important immune defenses. However, S. pyogenes exists in many distinct “serotypes,” each with its own version of the M protein. In this study, we explored whether tailored vaccines built around specific M protein variants (from multiple S. pyogenes strains) could confer significant protection from infection in a mouse model that mimicks critical elements of human immunity. Although combining these M protein variants with an immunity stimulating adjuvant (alum) boosted antibody production in the bloodstream, the vaccines did not effectively reduce bacterial colonization in the nasopharynx. In fact, only a limited antibody response was observed at the mucosal surface, where S. pyogenes typically initiates infection. These observations suggest that, even when aiming for serotype-specific immunity, current M protein–based vaccine strategies alone may not be sufficient for robust protection. Despite these setbacks, refining M protein vaccines remains a viable pathway for tackling the burden of S. pyogenes disease. By incorporating more potent mucosal adjuvants, optimizing how the M protein is presented, and targeting multiple serotypes simultaneously, future vaccine designs could better prevent S. pyogenes from taking hold in the upper respiratory tract.
Recommended Citation
Ali, Salman, "Assessing Intranasal M Protein–Based Vaccines Against Streptococcus pyogenes: Serotype-Specific Constructs and Mucosal Immunity in a B6HLA Mouse Model" (2025). Electronic Thesis and Dissertation Repository. 10742.
https://ir.lib.uwo.ca/etd/10742