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Intranasal Vaccine Effective in Murine Model

2001 FEB 6 - (NewsRx.com & NewsRx.net) -- - by Michelle Marble, staff medical writer -- Researchers in Sweden demonstrated the efficacy of a group B Streptococcus type III polysaccharide-cholera toxin B subunit conjugate intranasal vaccine in a preclinical murine model.

"Streptococcus group B (GBS) is usually carried asymptomatically in the vaginal tract of women and can be transferred to the newborn during parturition," wrote X.Z. Shen and colleagues, Gothenburg University. "Serum antibodies to the capsular polysaccharide (CPS) can prevent invasive diseases, whereas immunity acting at the mucosal surface may be more important to inhibit the mucosal colonization of GBS and thus the risk of infection for the newborn.

"We prepared different GBS type III CPS-protein conjugate vaccines and evaluated their systemic and mucosal immunogenicity in mice," wrote the authors. "GBS type III CPS was conjugated to tetanus toxoid (TT) or recombinant cholera toxin B subunit (rCTB) either directly or to rCTB indirectly via TT."

The researchers conjugated the vaccines by three different methods: (1) they coupled CPS to TT with 1-ethyl-3 (3-dimethylaminopropyl)-carbodiimide (EDAC) were adipic acid dihydrazide (ADH) was used as a spacer; (2) they conjugated CPS with rCTB using reductive amination; or, (3) they used N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) to bind rCTB to the TT of the CPS-TT conjugate.

They vaccinated mice with one of the three conjugates or with purified CPS by either subcutaneous (s.c.) or intranasal (i.n.) routes. They then measured antibodies to GBS III in the serum, lungs, and vagina via an enzyme-linked immunosorbent assay.

Results showed that all three CPS-protein conjugates were superior to unconjugated CPS in eliciting CPS-specific immune responses in serum and mucosal tissue extracts.

The results showed that when conjugates were administrated s.c., they only induced immunoglobulin E (IgE) responses in serum, lung, and vagina. Intranasal administration, however, elicited additional immunoglobulin A (IgA) responses in the lungs and vagina.

When the CPS-TT conjugate was given i.n., it induced a strong serum IgG, but only a weak mucosal IgA response, reported the authors. Intranasally administered CPS-rCTB conjugate elicited high IgG as well as high IgA antibodies in the lungs.

When GBS III CPS-TT was conjugated with rCTB and administered i.n., it produced a strong systemic and local anti-CPSIII response.

When CT was co-administered as an adjuvant, it further enhanced the anti-CPS systemic and mucosal immune responses after i.n. administration with the CPS conjugates.

"These findings indicate that: (i) i.n. immunization with GBS CPS-protein conjugates was more effective than s.c immunization for stimulating serum as well as mucosal immune responses; (ii) rCTB as a carrier protein for GBS III CPS could markedly improve the mucosal immune response; and (iii) the experimental GBS type III CPS conjugates containing rCTB should be investigated as mucosal vaccine to prevent GBS infection in humans," concluded Shen et al. ("Preparation and preclinical evaluation of experimental group B Streptococcus type III polysaccharide-cholera toxin B subunit conjugate vaccine for intranasal immunization," Vaccine, 2000;19(7-8):850-861

The contact person for this report is T. Lagergard, Gothenburg University, Department of Medical Microbiology & Immunology, Guldhesgatan 10, S-41346 Gothenburg, Sweden.

A search at NewsRx.net using the search term "group B strep" yielded over 19 articles in 20 specialized reports.

Key points reported in this study include:

* A group B streptococcus (GBS) type III polysaccharide-cholera toxin B subunit conjugate intranasal vaccine was evaluated

* Capsular polysaccharide protein conjugates were administered intranasally or subcutaneously

* A preclinical murine model demonstrated the efficacy of the intranasal approach

This article was prepared by TB & Outbreaks Week editors from staff and other reports.

©Copyright 2000, TB & Outbreaks Week via NewsRx.com & NewsRx.net

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