Protective Studies with a Group A Streptococcal M Protein Vaccine. II. Challenge of Volunteers after Local Immunization in the Upper Respiratory Tract

Abstract

Twenty-one adult volunteers were immunized at monthly intervals with three doses of purified type 1 M protein of group A Streptococcus. The soluble vaccine in buffer was administered by aerosol spray into the nares and oropharynx; 23 control subjects received a buffer placebo in the same manner. Antibody responses were observed in sera and nasal washings of some but not all vaccines. Approximately 30 days after the last dose, all subjects were challenged with homologus streptococci applied by swab to the phayngeal-tonsillar areas. In a double-blind system of evaluation, physical signs and symptoms were followed for assessment of infection. Illness was defined on the basis of a positive throat culture, fever, a twofold increase in white blood cell count over baseline, exudative pharyngitis, and cervical adenopathy. By these criteria four vaccinees and 11 controls were obviously ill. One vaccinee and six controls were questionably ill, fulfilling some but not all of the criteria. sixteen vaccinees and six controls were not ill (P less than 0.001). Positive throat cultures were observed in five vaccines and 19 controls (P less than 0.001). Penicillin was administered five days after challenge. No poststreptoccal sequelae or other complication were observed. Thus local immunization with M protein apparently can prevent both colonization and clinical illness after challenge with homologous streptococci.

Disease Manifestations and Pathogenic Mechanisms of Group A Streptococcus

“…Historical studies administered crude whole M protein preparations to human volunteers, which was followed by challenge with live GAS bacteria in the pharynx. While these preparations decreased GAS colonization (530)(531)(532), an increased incidence of ARF was reported for some of the immunized subjects (533). Several recent M-protein-based studies have investigated the protective efficacy of the N-terminal hypervariable region (338,444,(534)(535)(536)(537)(538)(539), as this region may not be involved in autoimmune disease.…”

Affinity purification and characterization of a fibrinogen-binding protein complex which protects mice against lethal challenge with Streptococcus equi subsp. equi

“…These dimeric, fibrillar molecules bind several host proteins including fibrinogen (Fg), albumin and IgG, are clearly major antiphagocytic virulence factors, and may have a role in adhesion (Kehoe, 1994;Hasty et al, 1992;Fischetti, 1991). There is also a large body of evidence to suggest that they are protective (Bronze et al, 1992(Bronze et al, , 1988Bessen & Fischetti, 1990;D'Alessandri et al, 1978;Polly et al, 1975). Other protective cell-wall-associated proteins include the fibronectin (Fn)-binding protein of staphylococci (Schennings et al, 1993), the pneumococcal PspA protein (AlonsoDeVelasco et al, 1995) and the Streptococcus nzutans surface protein antigen 1/11 (Katz et al, 1993;Okahashi et al, 1989).…”

Clinical and Microbiological Responses of Volunteers to Combined Intranasal and Oral Inoculation with a Streptococcus gordonii Carrier Strain Intended for Future Use as a Group A Streptococcus Vaccine

“…An advantage of constructing a group A streptococcal vaccine that delivers antigens directly to the mucosal surface (the primary site of natural infection) is that antigen-specific secretory immunoglobulin A can be maximally stimulated. Human challenge studies conducted in the 1970s suggested that purified M protein vaccines elicit higher levels of protection against both illness and infection when delivered mucosally (intranasally plus orally) rather than parenterally (6,26). Nonetheless, a live mucosal group A streptococcal vaccine poses certain safety concerns that stem from the observation that acute rheumatic fever follows ca.…”