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Vaccines: An innovative approach to combating antimicrobial resistance
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In 2013, President Barack Obama identified antimicrobial resistance as a significant public health concern in the United States. He then requested guidance from the President’s Council of Advisors on Science and Technology on how to address this growing issue. The result of this effort was recently released and the recommendations can be summarized as follows:
- slow the development of resistant bacteria and prevent the spread of resistant infections;
- strengthen national One-Health surveillance efforts to combat resistance;
- advance development and use of rapid and innovative diagnostic tests for identification and characterization of resistant bacteria;
- accelerate basic and applied research and development for new antibiotics, other therapeutics and vaccines; and
- improve international collaboration and capacities for antibiotic resistance prevention, surveillance, control, and antibiotic research and development.
The ongoing and proposed interventional efforts under discussion by government, scientific leaders and professional organizations are highly focused on the development of new antibiotics as a solution to antimicrobial resistance (AMR). What about vaccines? The value of vaccines is incontrovertible; they have played an essential role in preventing and quelling infectious disease outbreaks of public health importance around the world. Vaccines have been so successful that some pathogens, such as Haemophilus influenzae and pneumococcal pneumonia, are not even part of the conversation regarding the threat of AMR. Given these great successes, why aren’t we focusing on vaccines as a way to combat AMR? This article will discuss three possible reasons for this omission as well as a potential solution.
Unique characteristics of the organisms of concern
A review of the organisms for which antimicrobial resistance is considered an “urgent” or “serious” threat might help explain the paucity of references to vaccines and the emphasis on antibiotics (see Table). Many, although not all, bacteria driving the most concern are hospital-associated/acquired infections. Generally, an outbreak of one of these microbes is small, localized and unanticipated. Even if these pathogens are found in a community setting, a vast majority fall into the same small, localized and unanticipated category. These outbreaks need to be controlled immediately for many reasons, including the safety and health of the compromised subpopulation. But other motivators, such as the community or health care services who commonly expect an immediate solution to this type of problem, can also influence decisions regarding investment in vaccine or therapeutic development.
Challenges to vaccine development
The vaccines that were straightforward to develop and implement are already being utilized, and the vaccines that are not yet developed are those that present significant challenges. In some ways, the challenges for the AMR organisms of significant concern are similar to the challenges we face for all future vaccines. We need to better understand immune correlates, identify antigens required to mount and maintain an appropriate immune response, and recognize the significant amount of time and money associated with the development process. Many, but not all, of the “pathogens” of the greatest concern have the added complexity of also being associated with a normal, healthy human flora. Their role, however, is unclear. We can accept and address, through antibiotics, the necessary disruption in equipoise when these organisms cause harm in an at-risk individual. However, we understand very little about what would happen if these organisms were eliminated through vaccination in the healthy population.
The issues surrounding the word ‘vaccine’
When one talks about developing a “vaccine,” they mean more than just developing the biomedical product; they also mean producing a product used for “public health” purposes. With that meaning comes layers of regulations, policies and implementation complexities. Vaccines, simply stated, are intended for broad use across a large population with the goal of controlling highly transmissible diseases. The expectation is that vaccination of large numbers of susceptible individuals at an affordable cost will result in transmission interruption and decreased risk for disease. The business decisions, regulatory pathway, state and federal subsidies and guarantee purchases all depend on this business model. It is important for us to gain a better understanding of how and whether this model is applicable to the pathogens considered of primary importance in AMR.
To circumvent some of these issues, would it be valuable to create a new category of products called “prophylactic immune interventions,” or PIIs? A PII could have the same product development challenges as a vaccine, but it may not require the same regulatory pathway or carry the same expectations as a vaccine (eg, durability of immune response). A PII could be a targeted intervention for only selective at-risk populations, such as candidates for elective surgery or other at-risk populations. Possibly part of a more comprehensive medical management plan, especially in the hospital setting, PIIs could expand the definition of “prophylactic” within the treatment world, and might also fall under a different cost/benefit evaluation equation. This type of product might be competitive with the drug/medical management space rather than the vaccine markets, and recommendations for use might be closer to therapeutic rather than vaccine guidelines. However, a PII would still take a preventive approach to controlling infectious diseases.
It is imperative that we use all possible avenues to address the rapidly growing problem of AMR. Perhaps it is time to start discussing a new method that utilizes the idea of vaccines — one of the most successful public health interventions in history — but with a focus on different, smaller target populations and also modified development, evaluation and implementation models. Now is the time to start this conversation.
- References:
- CDC. Antibiotic Resistant Threats in the United States, 2013. www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf. Accessed June 4, 2015.
- The White House. National Strategy for Combating Antibiotic-Resistant Bacteria. 2014. www.whitehouse.gov/sites/default/files/docs/carb_national_strategy.pdf. Accessed June 4, 2015.
- For more information:
- Carole Heilman, PhD, is the director of the Division of Microbiology and Infectious Diseases at the NIAID.
Disclosure: Heilman reports no relevant financial disclosures.