A Novel Live Vector Group A StreptococcalemmType 9 Vaccine Delivered Intranasally Protects Mice against Challenge Infection withemmType 9 Group A Streptococci

Abstract

ABSTRACTThe availability of a protective vaccine againstStreptococcus pyogenes(group AStreptococcus[GAS]) is a priority for public health worldwide. Here, we have generated six live vaccine strains, each engineered to express an N-terminal M protein peptide from one of six of the most prevalentemmtypes of GAS (M1, M2, M4, M9, M12, and M28). The vaccine strains are based on a food-gradeLactococcus lactisstrain and do not bear any antibiotic resistance. Mice immunized with the vaccine strain expressing the M9 peptide (termed here theL. lactisM9 strain) showed high titers of serum antibodies when delivered intranasally. Mice immunized with theL. lactisM9 strain were protected against infection after intranasal challenge with type 9 streptococci. Several parameters of disease, such as weight loss, body temperature, colony counts in mouth washes, and lung histology, were significantly improved in immunized mice compared to naive control mice. Our results indicate that intranasal delivery of theL. lactisM9 strain live bacterial vaccine induced GAS-specific IgG titers, prevented pharyngeal colonization of GAS, and protected mice from disease upon challenge. The design of this vaccine prototype may provide a lower cost alternative to vaccines comprised of purified recombinant proteins.