Recent research demonstrates the efficacy of a new vaccine against pneumonia caused by Staphylococcus aureus bacteria, offering hope for protection from the potentially deadly illness that affects approximately 50,000 people in the United States each year.
Investigators at the University of Iowa (UI) used a vaccine containing superantigens and cytolysins to target toxins produced and discharged by staph bacteria to successfully protect 86 of 88 vaccinated rabbits challenged intra-pulmonary with 9 different S. aureus strains compared with only 1 of 88 non-vaccinated rabbits.
The findings demonstrate the importance of vaccinating against secreted virulence factors instead of against antigens containing cell surface proteins — which actually enhanced disease severity in the study as indicated by infective endocarditis — for protection from S. aureus with multiple strains and clonal groups, including the drug-resistant Methicillin-Susceptible Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA).
"Our study suggests that vaccination against these toxins may provide protection against all strains of staph," said Dr. Patrick Schlievert, professor and chair of microbiology at the UI Carver College of Medicine. "If we can translate this finding into an effective vaccine for people, it could potentially prevent millions of cases of serious and milder skin and soft tissue infections each year."
Additionally, using serum from vaccinated rabbits to immunize other rabbits was successful in protecting against S. aureus, which, according to the researchers, suggested antibodies produced by the vaccine is an important mechanism of protection.
Why did this vaccine succeed where others failed? Previous experiments had involved mice and non-human primates, which the researchers pointed out are resistant to superantigens and moderately resistant to cytolysins. On the other hand, rabbits are similar to humans in that they are highly susceptible to the 2 secreted virulence factors, which are key participants in infections, and associated with significant morbidity and mortality. S. aureus strains in humans produce high levels of superantigens and at least 1 high-level cytolysin, explained the researchers, meaning their study is the first to include a major S. aureus virulence factor in human infections.
The researchers also anticipated that neutralizing superantigens and cytolysins would prevent serious disease and death, but not impact colonization of infection. However, the results showed rabbits developed sterilizing immunity a week after the S. aureus challenge, which suggests vaccination against secreted virulence factors may prevent colonization, reducing the ability of S. aureus to evade the immune system instead of resulting in the direct killing of the organism. Prior investigations targeted bacteria cell-surface factors that are key to colonization, which made immunization attempts ineffective.
The study was published in the Journal of Infectious Diseases.
Spaulding AR, Salgado- Pabón W, Merriman JA, et al. Vaccination against Staphylococcus aureus pneumonia. J Infect Dis. 2013 Dec 19. [Epub ahead of print]