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01-10-2009 | Gastroenterology | Article

TNF-α-inducing protein as a potential H. pylori vaccine

Abstract

Free abstract

MedWire News: A tumor necrosis factor (TNF)-α-inducing protein (Tipα) of Helicobacter pylori shows promise as a vaccine antigen against infection with the bacterium, researchers report.

They found that vaccination with the antigen inhibited the colonization of H. pylori mainly via T-helper (Th) 1 cell-mediated immunity.

“Tipα has the unique function of inducing TNF-α production by gastric cells in vitro and it is assumed to be related with the development of gastritis and gastric cancer,” explain Akira Nishizono (Oita University, Japan) and colleagues.

They immunized mice intranasally with the vaccine adjuvant CpG (cytosine and guanine), with recombinant Tipα plus CpG, or recombinant del-Tipα (a mutant of Tipα) plus CpG.

These mice, along with a control group of non-vaccinated mice, were then infected with H. pylori and the number of colonizing bacteria in the stomach was calculated and the histological severity of gastritis evaluated 8 weeks later.

Vaccination with Tipα and del-Tipα resulted in high titers of Tipα-specific immunoglobulin (Ig)G or IGgA antibodies. There was a significant reduction in colonizing bacteria compared with infection control mice, with average numbers of 4.29 x 105 colony forming units (CFU)/g of stomach tissue and 2.50 x 105 CFU/g versus 5.7 x 106 CFU/g.

The reduction in bacteria colonization in Tipα vaccinated mice was also significantly reduced compared with the CpG-immunized mice, indicating that the reduction was not caused by the CpG itself.

Although a more than 1 log CFU decrease in bacteria colonization compared with infection control mice was achieved, this was short of the 2-log reduction widely accepted as a benchmark of success. The researchers say that Tipα is only one of various virulence factors and might be a weaker antigen for single use.

“Combining Tipα with another virulence factor like UreB or VagA might be one solution to this problem,” they suggest in the journal Helicobacter.

Nishizono et al note that the Tipα-immunized mice had relatively severe gastritis with marked inflammation, compared with mild-to-moderate inflammation in the infection control mice. This would be a problem for the practical use of Tipα vaccines, but previous research has suggested that this post-immunization gastritis may be a temporary phenomenon that disappears with time.

Quantitative real time polymerase chain reaction revealed that del-Tipα-immunized mice had a significant increase in interferon-γ expression compared with infection control mice and an increase in interleukin-10 expression.

Thus, Tip vaccination appears to induce both Th1- and Th2-mediated responses, the researchers write, “but the Th1-dominant reaction contributed to the reduction in colonization.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

By Lucy Piper