Why Have Efforts to Vaccinate Against S aureus Failed?

Despite the sizable burden that Staphylococcus aureus has on patients and health care systems, efforts to develop a vaccine against the pathogen have been unsuccessful thus far.

But now, a new study published in The Journal of Clinical Investigation may offer some insight on why efforts to develop a vaccine for S aureus have failed. The investigators, who found that T cells play a key role in protecting against S aureus bacteria, even point toward future approaches which could yield better results.

Because S aureus infections recur more frequently when skin is a primary site of infection than in cases of invasive staphylococcal disease, it has been suggested that tissue-specific mechanisms mediate immunity. To reproduce this observation, investigators exposed mice to S aureus in order to model skin infection and bacteremia.

Mice exposed to skin infection had lesions which resolved by day 14. Bacteremic mice experienced weight loss and recovered over 12-14 days.

On day 40 of the study, mice were rechallenged with S aureus skin infection to compare tissue-specific immune responses.

Tissue pathology showed that intravenously challenged mice had smaller skin lesions during the secondary skin challenge than mice who had been exposed to primary skin infection.

Based on the role that S aureus a-toxin plays in skin infections, investigators evaluated the anti a-toxin response, finding that bacteremia elicited higher antibody levels against a-toxin and staphylococcal lysates compared to primary skin infection.

“We discovered a robust T cell response targeting staph [S aureus] in the bloodstream,” Juliane Bubeck Wardenburg, MD, PhD, senior author of the study and director of the Washington University School of Medicine’s Division of Pediatric Critical Care, said in a news release.

“By contrast, T cells were diminished in skin infections as a result of the toxin. Because skin infection is very common, we think that staph uses alpha-toxin to prevent the body from activating a T cell response that affords protection against the bacteria.”

Past vaccination development efforts for S aureus have focused on B cells rather than T cells.

The study authors believe that the bacteria shapes T cell response early on in life and noted that S aureus colonizes up to 50% of infants by 8 weeks. Therefore, they envisioned future strategies which focus on early life.

“One is immunizing pregnant women so they can transfer antibodies that protect infants against the toxin at birth. The second involves immunizing infants within a day or two after birth. Neither of these strategies has been considered for staph [S aureus] vaccines to date,” Bubeck Wardenburg said.

Investigators concluded that future research on T cell-mediated immunity and early human response to S aureus may provide valuable information for vaccine development efforts.