Pneumococcal vaccine: Development and prospects

Abstract

M ore than a year has elapsed since the iicensure and release of a polyvalent vaccine of pneumococcal capsular polysaccharides for the prevention of infection caused by the prevalent invasive pneumococcal capsular serotypes. It is estimated that approximately three million doses of vaccine have been distributed at the time of this writing. In view of the rather limited acceptance of this newly available prophylactic agent by physicians and the public, it may be timely to review briefly the history of pneumococcal disease in the nearly 100 years that have elapsed since the initial isolations of Streptococcus pneumoniae and to consider the role of pneumococcal vaccine in the light of what has been learned to date and of what problems remain to bc solved. The role of pneumococcus as a pathogen in man had been clearly elucidated by the end of the 19th century and the importance of lobar pneumonia as a cause of fatality typifier1 by Osler’s designation of it as “Captain of the men of death.” In an era of explosive development of knowledge concerning pathogenic microorganisms, much effort was devoted to the prevention and treatment of infectious disorders. Rational immunoprophylaxis and immunotherapy of pneumococcal infection, however, could not proceed until recognition of the diversity of pneumococcal capsular serotypes; and it was not until after the initial observations of Neufeld and Handel in 1910 that the first effective steps toward their development were undertaken. By the fourth decade of this century, considerable progress had been made in the isolation and rapid identification of pneumococcal capsular serotypes and in the development of type-specific therapy, first with equine antiserums, ancl later with rabbit antiserums. Considerable work had been carried out also in the area of immunoprophylaxis. With the introduction of sulfapyridine in the 1930’s and of penicillin in the following decade, physicians had available for the first time therapeutic agents of greatly improved efficacy, potent against pneumococci irrespective of their capsular type. The advent of these drugs led rapidly to the abandonment of immunologic approaches to the diagnosis and control of pneumococcal disease and to the all but total disregard of the contemporary epidemiology of such infections. Reevaluations of bacteremic pneumococcal infection in the 1950’s and 1960’s have shown [1,2], however, that, despite the marked improvement in prognosis resulting from therapy with antimicrobial drugs, significant mortality is still associated with such illness. These studies have led to the making available once again an immunoprophylactic vaccine for those at significant risk of pneumococcal infection with a fatal outcome. The vaccine, composed of the capsular polysaccharides of 14 pneumococcal types accounting for the preponderance of pneumococcal bacteremias (types 1, 2,3,4, GA, 7F, SN, UF, 14,18C, 19F, 23F and 251, has been shown to be 80 per cent effective in adults in the prevention of putative and proved pneumococcal infection associated with these capsular types [3]. Although there are no contraindications to immunization of any adult save pregnancy and intercurrent infection, administration of the vaccine to people over 60 years of age and to those over two years of age with any of a variety of chronic illnesses or asplenia is recommended because of their increased vulnerability to severe infection. Data collected since the release of the vaccine suggest that it has not been administered widely to these target populations [4]. It may be relevant, therefore, to review briefly what is known about the vaccine and what additional information might help to clarify further its role in medical practice. Most adults receiving the vaccine manifest an immunologic response to all its 14 antigens. Pneumococcal capsular polysaccharides are not biodegradable by mammalian enzymes, and antibodies to them persist for years. Because recurrent infection with the same pneumococcal capsular type in the normal adult is exccedingly rare, and because the decay of antibodies