Nonionic block polymer surfactants modulate the humoral immune response against Streptococcus pneumoniae-derived hexasaccharide-protein conjugates

Abstract

Nonionic block polymer surfactants (NBPs) were tested for the capacity to stimulate the antibody response against hexasaccharide (HS), derived from Streptococcus pneumoniae type 3 capsular polysaccharide (S3PS), which was conjugated to proteins. The immune response was evaluated in the (CBA/N x BALB/c)F1 progeny, in which female mice are phenotypically normal whereas male mice carry an X-chromosome-linked immunodeficiency. NBPs L101, L121, 1101, and 1501 were able to increase anti-HS immunoglobulin M (IgM) and IgG levels in both normal and X-chromosome-linked immunodeficient mice (with up to 74-fold stimulation of antibody titers). Distribution of S3PS-specific antibodies over the various IgG isotypes was restricted after immunization with either HS-bovine serum albumin or HS-keyhole limpet hemocyanin (HS-KLH). Addition of NBPs (in particular 1501) resulted in a more diverse immune response with either antigen as judged by isotype distribution. Isoelectric focusing of individual sera and subsequent detection of S3PS-binding antibodies in these sera by immunochemical staining revealed a restricted number of different spectrotypes in the course of the immune response. Upon immunization of mice with HS-KLH, spectra of secreted antibodies were slightly more complex and more densely stained than after immunization with HS-bovine serum albumin. Furthermore, NBPs 1101 and 1501 appeared to be able to stimulate the secretion of antibodies, which were secreted only in small amounts without the use of NBPs. Different explanations for increased spectrotype diversity after immunization with KLH as the carrier and after administration of NBPs as the adjuvant are discussed.

Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines.

“…The anti-saccharide Ab re-sponse induced by conjugates is in many aspects comparable to the TD responses to proteins (129) ( Table 2). Conjugates are immunogenic in infants (74,144), they induce memory (129), and the isotype restriction characteristic of TI-2 antigens is bypassed (132,134), especially when the conjugates are administered in combination with adjuvants (154,163).…”

“…Furthermore, clonal restriction, as shown for TI-2 responses, is still observed in response to conjugates. This phenomenon seems to be caused by the limitations of the B-cell repertoire; although conjugation to a protein indeed results in stronger activation of B cells and in extensive Ig (sub)class switching, the numbers of B-cell clones reactive with saccharides remain the same (74,163).…”

Alkyl Ethoxylated and Alkylphenol Ethoxylated Nonionic Surfactants: Interaction with Bioactive Compounds and Biological Effects

“…Tween 80 modified invertase secretion by Neurospora crassa and the cell-wall-less slime secreted by an N. crassa mutant(62). Polyethylene oxide-polypropylene oxide block-polymers up to 7.90 Da molecular mass stimulated the secretion of antibodies against Streptococcus pneumoniae-derived hexasaccharide-protein conjugates (63). The same block-polymers enhanced the avidity of antibodies in polyclonal antisera against Streptococcus pneumoniae type 3 in normal and Xid mice (64).…”

Meningococcal lipopolysaccharide (LPS)-derived oligosaccharide-protein conjugates evoke outer membrane protein- but not LPS-specific bactericidal antibodies in mice: influence of adjuvants

“…The biological functionality of an antiserum is determined by the amount, epitope specificity, avidity, and (sub)class distribution of the antibodies present. As indicated in previous studies, these properties can be influenced by adjuvants such as Quil A or the nonionic block polymer L121 (1,31,46,50,52). Therefore, we investigated the immunological properties of the conjugates prepared and the purified OMP in combination with these adjuvants.…”