Exploring the Future of Vaccines for HAIs

A recent review article published in Clinical Infectious Diseases on the status of vaccines in development for healthcare associated infections (HAIs) provides both an in-depth discussion of their urgent need, as well as their potential for success.¹ The review focuses on the burdens associated with HAIs and the clinical data available on new vaccines intended to protect us from the most common of these infections.

In the review, first author Jane M. Knisely, PhD, from the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases in Rockville, Maryland and her colleagues, describe the, "... promise, challenges, and current pipeline of vaccines to prevent HAIs." To accomplish this, the review addresses topics including antimicrobial resistance, HAI-associated morbidity and mortality, and relevant findings regarding the efficacy and safety of vaccines in development against Clostridium difficile (C. diff), Staphylococcus aureus (S. aureus), gram-negative HAIs, and candida. Additionally, passive immunization through the use of monoclonal antibodies is discussed. The review concludes with a discussion of the challenges that will face vaccine developers as they continue to struggle with HIAs.

In a discussion regarding the relationship between antimicrobial resistance and healthcare settings, Knisely et al, explain how high population healthcare facilities are more likely to harbor an increased density of bacterial and fungal pathogens than non-healthcare settings. This density becomes very problematic in an environment where high-risk patient populations are concentrated. Additionally, the presence of indwelling devices, such as catheters, can contribute to the transmission of pathogens. Perhaps the most well-known risk associated with high population healthcare facilities is the high level of broad spectrum antibiotics usage, which serves as a foundation for antimicrobial resistance.

Regarding the morbidity and mortality associated with HAIs, Dr. Knisely and her colleagues cite a 2013 report issued by the Centers for Disease Control and Prevention which estimated more than 2 million infections and 23,000 deaths per year attributable to resistant bacterial and fungal infections.² Among the most lethal of the HAIs, C. diff was reported to have caused 453,000 illnesses and was associated with approximately 29,000 deaths in 2011.³ C. diff is particularly dangerous in high population healthcare facilities, as it can establish itself by taking advantage of the gut dysbiosis associated the with the frequent use of broad-spectrum antibiotics in these settings.

The majority of the review is devoted to descriptions of HAI-directed vaccines in development. In their assessment of the evidence to date on C. diff vaccines in development, Dr. Knisely and colleagues posit that, "... an effective vaccine against this major nosocomial infection appears within reach." As for S. aureus, the authors concluded that the accumulated data provided some hope for the development of a safe and efficacious vaccine, although it would only be a part of a regimen involving passive immunotherapy and antimicrobials. The data on Gram-negative HAIs are less encouraging, with only one Gram-negative species, P. aeruginosa, having a vaccine candidate, IC43, that has moved from Phase I clinical development to a Phase II/III trial. Candida has two vaccine candidates in Phase II testing, although the authors point out that they are being developed for a specific candida infection, vulvovaginal candidiasis, and therefore may not be effective for systemic disease.

In the discussion of passive immunization, Knisely et al describe clinical trials for both prophylactic and therapeutic indications as "... challenging to design and expensive to conduct," but also note that recent increases in public and private investment in the development of such agents should be cause for optimism.

Among the challenges cited for the future of HAI vaccine development, Knisely and colleagues stated that, "While there are vaccines in Phase I and II testing for other HAI pathogens, vaccine development is a high-risk endeavor and several S. aureus vaccine candidates have already failed in Phase II/III testing." They suggest that new vaccine development will depend on the ability of researchers to conduct and translate basic studies on correlates of protection, which are currently lacking, as well as on the adoption of strategies to improve responses to vaccines in the elderly and immunocompromised populations due to their high risk status.

The review ends on a hopeful note, with the authors stating, "Despite the challenges involved in developing vaccines and other prophylactic immune interventions, they are a promising potential addition to the arsenal of tools to combat this major public health problem."

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.

References

1. Knisely JM, Liu B, Ranallo RT, Zou L. Vaccines for Hospital-Associated Infections: Promise and Challenge. Clin Infect Dis 2016 May 20. pii: ciw333. [Epub ahead of print].
2. CDC. Antibiotic Resistant Threats in the United States 2013. Available at: www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed May 27, 2016.
3. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Engl J Med 2015;372:825—34.