Is development of a S. aureus vaccine a realistic goal?

A vaccine targeting specific high-risk patients will be difficult, but possible.

Skin and soft tissue infections caused by CA-MRSA strains are not the most serious infections for which we need protection by a vaccine. Many physicians are hesitant to treat abscesses with antibiotics, much less develop a vaccine to prevent them.

As CA-MRSA strains replace certain hospital strains, patients with risk factors for more serious infections are affected. Thus, the emergence of CA-MRSA has engendered a search for alternative approaches to control it.

Vaccines have been successful against other important pathogens like pneumococci and Haemophilus influenzae. The success of those vaccines has pushed the limitations of antibiotic therapy, and treatment of serious, life-threatening MRSA infections has sparked a renewed interest in development of a staphylococcal vaccine. S. aureus is an important pathogen that’s killing and affecting a lot of people. If we put a lot of resources into development of a vaccine it will not be impossible, just harder than most.

My personal bias is that it’s going to have to be a multicomponent vaccine that includes capsule polysaccharide and staphylococcal surface proteins. I think clumping factor A and IsdB currently have the strongest data to support their inclusion in an S. aureus vaccine. The addition of at least one toxin component makes sense, and alphatoxin would certainly be my first choice for that. Poly-N-acetyl glucosamine may be another good vaccine component. I think those are the most promising candidates to date.

There are many challenges to developing an effective vaccine. S. aureus causes many types of infections, so is a single vaccine going to protect against multiple kinds of infections?

We don’t yet understand the protective correlates of immunity to staphylococcal infections. We have no idea what constitutes immunity to staphylococci or even if that is an achievable goal. Individuals don’t recover from a CA-MRSA infection and become immune to re-infection. Certain individuals succumb to recurrent infection. Presumably we need certain levels of protective antibodies to critical staphylococcal antigens, but we don’t understand yet which antigens are the necessary ones.

There are many academicians and corporate entities now that are working on the development of an S. aureus vaccine. Sufficient effort put toward this goal will likely result in a vaccine against MRSA. It may not protect against all facets of staphylococcal infection, but I really do think an effective vaccine is possible. I suspect it could take seven to 10 years because these things take a long time, and there are no vaccine candidates that are even close right now.

Jean C. Lee, PhD, Associate Professor of Medicine at Harvard University and Associate Microbiologist in the Department of Medicine at Brigham and Women’s Hospital, Boston.

Past attempts not promising, but further study is worthwhile.

Recent vaccine efforts have been disappointing. During the ’50s and ’60s David E. Rogers, MD, a leading expert in staphylococcal diseases, predicted that there would be little hope of augmenting the humeral immune response to S. aureus, because almost all humans have “impressive humoral immunity to staphylococcal disease” and “all normal adults possess opsonizing antibody that induces prompt phagocytosis of staphylococci.” Right now that would be my current view.

A multifactorial approach, in which several of the secreted toxins known to promote disease are targeted by neutralizing antibodies, may work well for treating and possibly preventing severe staphylococcal syndromes. However, this approach might only work for specific diseases and for passive immunization so it would be necessary to recognize disease early in order to start prompt treatment. That said, such an approach certainly has merit.

It may also be possible to augment killing of staphylococci once they are ingested by white cells, but it remains to be determined whether some opsonizing antibodies — all else being equal — are better than others at activating the staphylocidal activity of phagocytic leukocytes. If two or more antibodies each recognize the target and promote uptake, then how are these similar molecules going to elicit a different immune response in the same cell? In the end, the same sets of host receptors are engaged. However, if it were possible to enhance bactericidal activity (independent of uptake) by using a certain antibody or set of antibodies, such an approach would be most interesting.

It is definitely worth putting effort into a staphylococcal vaccine because staphylococcal infections are the most abundant cause of bacterial infections in the United States and a leading cause of mortality. Further, a successful vaccine approach would perhaps circumvent the treatment problems associated with MRSA or CA-MRSA infections.

Frank R. DeLeo, PhD, Acting Chief, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, Rocky Mountian Laboratories in Hamilton, Montana.