AIDSWEEKLY Plus, Monday, 5 May 1997
Daniel J. DeNoon, Senior Editor
A genetically engineered vaccine against dental cavities induces T helper cells in the gut, stimulating the common mucosal immune system and resulting in circulating and mucosal antibodies.
The vaccine targets the dental cavity-causing bacteria Streptococcus mutans, which sticks to teeth via an adhesin on its surface called AgI/II (also known as antigen B, P1, SpaP, and PAc). The saliva-binding region (SBR) of AgI/II is therefore an attractive vaccine antigen.
But to stimulate antibodies where they will do the most good, a dental vaccine has to elicit secretory immunoglobulin A (sIgA) in the saliva. This must be done by stimulating the common mucosal immune system.
Because the nontoxic B subunit of the cholera toxin (CTB) is a potent inducer of this type of immunity, a research team at the University of Alabama has genetically engineered Escherichia coli to produce a chimeric protein - dubbed SBR- CTA2/B - in which the SBR is coupled to pentameric CTB by the cholera toxin CTA2 peptide (Hajishengallis et al., J Immunol, 1995;154:4322-32).
Now Nozomu Toida, Michael W. Russell, and colleagues have shown that SBR-CTA2/B can initiate a cascade of common mucosal immune responses in vivo.
"Coupling SBR to CTB in the form of SBR-CTA2/B chimeric protein enhanced its immunogenicity with respect to T-cell responses in PP [Peyer's patches] and MLN [mesenteric lymph nodes], and the addition of CT [cholera toxin] as an adjuvant further elevated these responses," Toida et al. reported. "The cytokine expression pattern in PP and MLN cells from mice indicated that T-cell help was skewed toward Th2 activity."
Toida et al. reported their findings in the journal Infection and Immunity ("Oral Immunization with the Saliva- Binding Region of Streptococcus mutans AgI/II Genetically Coupled to the Cholera Toxin B Subunit Elicits T-Helper-Cell Responses in Gut-Associated Lymphoid Tissues," Infect Immun, 1997;65:909-15).
The T-helper type 2 or Th2 immune-response profile seen in response to SBR-CTA2/B is associated with high levels of serum IgG and mucosal IgA antibody responses.
"The genetically constructed SBR-CTA2/B chimeric protein, in which the toxic CTA1 subunit has been deleted, is clearly able to induce mucosal and circulating antibodies without the necessity for additional CT," Toida et al. concluded.
"The enhanced enteric immunogenicity of SBR-CTA/2B chimeric protein, even in the absence of CT, is advantageous for an oral vaccine, as recombinant CTB has been shown to be a safe and effective immunogen in humans."
This work was supported by PHS grant DE06746 from the National Institute of Dental Research.
The present address for Dr. Toida is 67 Hirao jousui- machi, Chuo-ku, Fukuoka 810, Japan.
The corresponding author for this study is Michael W. Russell, Department of Microbiology, Box 1, University of Alabama at Birmingham, 845, 19th St. South, Birmingham, Alabama 35294-2170. Phone: (205) 934-4480. Fax: (205) 934- 7644. Email: medm012@uabdpo.dpo.uab.edu.
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