Chi-Jen Lee, ScD, Lucia H. Lee, MD, Kaio Koizumi, PhD

Abstract

Protective immunity to encapsulated bacteria involves an antibody response to a polysaccharide (PS) antigen, interactions with T and B lymphocytes, and host defense mechanisms. PS vaccines, such as those developed against Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, and Salmonella typhi, prevent infection by inducing an immune response against specific capsular polysaccharides. These vaccines, however, provided little protective immunity in infants and young children. The development of glycoconjugate vaccines overcame many limitations associated with PS vaccines by eliciting a quantitatively and qualitatively different immune response. Alternative strategies intended to enhance an immune response in infants include maternal immunization with PS or conjugate vaccine and hormone treatment during the critical period of neonatal development.

Introduction

Encapsulated bacteria are important pathogens that cause disease especially among infants, the elderly, and immunocompromised persons. Despite antibiotic treatment, the mortality and morbidity from bacteremia, meningitis, and pneumonia caused by these organisms are still high in these populations.^[1-3] The mechanism by which almost all encapsulated bacterial pathogens cause disease in children involves virulence factors such as surface capsular polysaccharides (PSs). The PS antigens contained in vaccines in the past, however, were poorly immunogenic and did not induce protective immunity in children younger than 18 months.

The need to improve protective immunity in populations at highest risk resulted in the development of conjugate vaccines. The coupling of PS antigens to a carrier protein overcame the immunologic limitations encountered with PS vaccines. The conjugation of Haemophilus influenzae type b (Hib) PS to diphtheria toxoid, tetanus toxoid, meningococcal outer membrane protein, or mutant diphtheria protein CRM197 and subsequent vaccination with Hib PS as a glycoconjugate vaccine successfully resulted in a more than 97% reduction of Hib disease in Finland, the United Kingdom, and the United States.^[4,5] Using the same carrier proteins contained in the Hib conjugate vaccines led to the development of meningococcal monovalent and bivalent conjugate vaccines and multivalent pneumococcal PS conjugate vaccines.

This first part of a 2-part article discusses the rationale for the development of conjugate vaccines and reviews the status and clinical effectiveness of vaccines against Neisseria meningitidis and Streptococcus pneumoniae. Part 2, in a future issue of Infections in Medicine, will cover vaccines against Hib and Salmonella typhi as well as the potential for vaccines against diseases caused by other encapsulated pathogens.