Antigenicity of the M proteins of group A hemolytic streptococci. 3. Antibody responses and cutaneous hypersensitivity in humans.

Highly purified M proteins were used for determining cutaneous hypersensitivity and type-specific circulating antibodies in normal adults and infants. 80% of 91 adults and 8% of 59 infants exhibited a transient delayed cutaneous reaction to at least two of types 12, 14, and 24 M proteins. Antibodies assayed by passive hemagglutination were observed in 90% of the adults and 13% of the infants. Vaccines of 10 microg of alum-precipitated M protein or 20 microg of the soluble antigen were administered to adults not exhibiting delayed hypersensitivity. Within 2 wk hemagglutination liters increased significantly in 31 of 33 subjects. Preimmunization antibody levels indicated that these responses were probably anamnestic reactions from previous exposures to homologous serotypes of group A streptococci. Sera exhibiting large increments in antibody titers resulting from M protein inoculations also had type-specific bactericidal properties. "Attenuated" M proteins, produced by partial degradation with trypsin induced only minimal cutaneous reactions in hypersensitive adults, but still retained most of the antigenic specificity when assayed in vitro and in vivo. The utility of M protein vaccines for human use is discussed in reference to the low incidence of cutaneous hypersensitivity in infants, the potentials of polyvalent attenuated M protein vaccines and the apparent absence of immune cross-reactivity between pure M proteins and human heart and kidney tissues.