Immunogenicity of Streptococcus pneumoniae type 14 capsular polysaccharide: influence of carriers and adjuvants on isotype distribution

Abstract

This project investigated the effects of novel carriers and adjuvants on the isotype of murine immunoglobulin G (IgG) antibody to pneumococcal capsular polysaccharide type 14 (S14PS). S14PS conjugated to bovine serum albumin induced a weak antibody response which was 100% IgGl following injection without adjuvant. The same polysaccharide conjugated to flagella of Salmonella typhi induced an antibody response which was 88% IgG3. S14PS-bovine serum albumin was injected with block copolymer L121 or Quil A in squalane-in-water emulsions. The copolymer L121 was at least as effective as Quil A or complete Freund adjuvant in inducing IgG antibodies. IgGl was the dominant subclass for all. Addition of monophosphoryl lipid A, but not the threonyl derivative of muramyl dipeptide or nontoxic Rhodopseudomonas sphaeroides lipopolysaccharide, to copolymer L121 increased production of the IgG2a, IgG2b, and IgG3 subclasses. S14PS-flagella with copolymer L121 induced higher titers with a markedly altered isotype distribution: 13% IgGl, 52% IgG2a, 6% IgG2b, and 29% IgG3. Monophosphoryl lipid A added to L121 reduced IgGl antibody to 5%, but increased IgG2a antibody to 14%, IgG2b antibody to 3%, and IgG3 antibody to 78%. These studies demonstrate that both the carrier and the adjuvant can influence the titer and isotype distribution of antipolysaccharide antibody responses. 2750 on July 16, 2020 by guest http://iai.asm.org/ Downloaded from

Partial Protection againstPlasmodium vivaxBlood-Stage Infection inSaimiriMonkeys by Immunization with a Recombinant C-Terminal Fragment of Merozoite Surface Protein 1 in Block Copolymer Adjuvant

“…Both humoral and cellular immune responses are necessary for an effective malaria vaccine against blood-stage parasites (29,40). One way to influence the host immune responses to an antigen is by the use of adjuvants (1,19,23,25,45). Immunization studies with C-terminal fragments of P. falciparum MSP-1 in primate malaria models showed that no protection was induced when an Escherichia coli-expressed 19-kDa antigen was formulated in aluminum hydroxide (alum) and liposomes (5).…”

Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin

“…As with other polysaccharides, covalent attachment of Pnl4 to a protein conferred enhanced immunogenicity and T-cell dependence (booster responses [31]). van de Wijgert et al prepared conjugates of Pnl4 with bovine serum albumin or the flagella of Salmonella typhi by a scheme similar to one described by us (9,38). Injection of 100 ,ug of these Pnl4 conjugates elicited serum antibodies in mice.…”

“…The development of polysaccharide protein conjugates for prevention of systemic infections caused by Haemophilus influenzae type b serves as a precedent for making conjugates of polysaccharides of other capsulated pathogens (31). This technology has been extended to improve the immunologic properties of other polysaccharides of medically important organisms such as Streptococcus pneumoniae (5,9,10,25,26,31,38,39). Since the objective is to provide protection against many capsulated bacterial pathogens of infants and children, investigators have used established vaccines such as diphtheria and tetanus toxoids or potentially protective antigens such as the toxoids of Pseudomonas aeruginosa exotoxin A and pneumococcal hemolysin (3,7,23,24).…”

Influence of Immunopotentiators on the Antiporin Immunoglobulin G Subclass: Distribution and Protective Immunity Against Murine Salmonellosis

“…It is evident from passive transfer experiments that protection might not be possible with a mere increase in antiporin antibody titre alone. Several studies [14,[25][26][27] indicate the strong influence of adjuvants on antibody isotypes generated in vivo. Hence, the subclasses of antibodies induced were analysed to understand the importance of quality of antibodies induced.…”

“…Moreover, it has been well established that antibody isotype is an important parameter in determining the protective efficiency of vaccines against invading pathogens. The vaccine efficacy thus depends not only on the titre but also on the class and isotype of antibodies induced [14]. Therefore, it is important to analyse and compare the antiporin IgG subclass antibodies induced by various porin-immunopotentiator preparations in terms of protection against murine Salmonellosis.…”