Secondary and Apparent Primary Antibody Responses After Group A Streptococcal Vaccination of 21 Children

Abstract

A partially purified M protein, extracted from a mouse-virulent strain of type 3, group A streptococcus, was administered subcutaneously in gradually increasing amounts at weekly intervals to 21 children in a Family Program. Seven children with type 3 bactericidal antibody in prevaccination sera showed a secondary response. Of 14 children with no detectable type 3 bactericidal antibody prior to vaccination, 13 developed definite type 3 antibody during or soon after vaccination. This response appeared to be of the primary variety in at least some of the 13 children because (i) the total incidence of antibody response (20 of 21) was greater than can be accounted for by the documented incidence of clinical and subclinical type 3 infections among children of our Family Program during a period of 14 years, (ii) the response in the 13 children with no detectable antibody prior to vaccination was more delayed than in those showing a definite secondary response, and (iii) on the average, the amount of vaccine needed for a response in these 13 children was 15 to 28 times greater than that required for the secondary response. Local skin reactions were variable among the vaccinated children. Systemic reactions were infrequent and not severe. The giving of multiple injections of partially purified M protein did not seem to cause cutaneous hypersensitivity.

Human immune response to immunization with a structurally defined polypeptide fragment of streptococcal M protein.

“…Indeed, the M antigen was first suspected as being haptenic until its antigenicity was confirmed by its administration to animals in larger doses (33). Most investigators have been disappointed with their inability to achieve a high percentage of primary immune responses in man with the doses of vaccine to which their regimens were confined (34)(35)(36)(37)(38)(39)(40)(41). For example, Schmidt (34) was only able to achieve a primary immune response in 2 of 24 children who received a total dose of 300 gg of alumprecipitated type 19 acid-extracted M protein.…”

Advances in Potential M-protein Peptide-Based Vaccines for Preventing Rheumatic Fever and Rheumatic Heart Disease

“…However, once S. pyogenes was identified as the organism responsible for RF and RHD, vaccine research focused on the M-protein. During the 1960s and 1970s multiple studies were conducted using purified M-protein or M-protein derivates in adults (17,18) and children (19,20) with mixed results. However, several studies reported adverse side effects (21,22).…”

Safety of Streptococcus pyogenes Vaccines: Anticipating and Overcoming Challenges for Clinical Trials and Post-Marketing Monitoring

“…There is a long history of vaccine trials for S. pyogenes in humans, dating back more than 100 years and involving more than 200 000 participants. One trial, conducted by Massell and colleagues in the United States in the 1960s, raised safety concerns, including with US regulators [ 12 , 13 ]. Over the past 2 decades, there have been 5 S. pyogenes vaccine clinical trials conducted.…”

“…The Massell study was conducted between 1965 and 1967 in Boston [ 12 , 13 ]. The vaccine was a hot-acid extracted M protein of a type 3 S. pyogenes , partially purified using ribonuclease and dissolved in thiomersal.…”