Prototype Pathogen Approach for Vaccine and Monoclonal Antibody Development: A Critical Component of the NIAID Plan for Pandemic Preparedness

Abstract

Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) emerged 20 years ago, presaging a series of subsequent infectious disease epidemics of international concern. The recent emergence of SARS-CoV-2 has underscored the importance of targeted preparedness research to enable rapid countermeasure development during a crisis. In December 2021 the National Institute of Allergy and Infectious Diseases (NIAID), building upon the successful strategies developed during the SARS-CoV-2 response and to prepare for future pandemics, published a pandemic preparedness plan that outlined a research strategy focused on priority pathogens, technology platforms, and prototype pathogens. To accelerate the discovery, development, and evaluation of medical countermeasures against new or previously unknown pathogens of pandemic potential, we present here a strategy of research directed at select prototype pathogens. In this manner, leveraging a prototype pathogen approach may serve as a powerful cornerstone in biomedical research preparedness to protect public health from newly emerging and reemerging infectious diseases.

Keywords: monoclonal antibody; pandemic preparedness; platform technologies; prototype pathogen; vaccine.

Figure 1.

National Institute of Allergy and Infectious Diseases (NIAID) prototype pathogen approach: prototype selection, research and development, and clinical trials. Prototype pathogens (one or a few from a family) will be selected for additional study from viral families of concern with input from subject matter experts. Once selected, characterization of the prototypes will be performed to understand pathogen biology, examine host immunity, develop animal models, and study pathogenesis, among other research and development efforts. Promising medical countermeasures (MCMs)—developed based upon viral characterization—will move into clinical trials. The goal of the prototype pathogen strategy is to use a generalizable MCM approach that can be applied to other members of the same viral family. Initial prototype pathogens were selected at a NIAID workshop held in November 2021. Figure adapted from the NIAID Pandemic Preparedness Plan [4].

Figure 2.

Comparison of pandemic potential and countermeasures for viral families known to infect humans. Viral families were categorized as having either low/moderate or high pandemic potential and low/moderate or high levels of existing resources and countermeasures. Cross-comparison revealed 10 viral families with high pandemic potential and low/moderate existing resources or countermeasures upon which National Institute of Allergy and Infectious Diseases (NIAID) will focus its pandemic preparedness activities. *Existing vaccine solutions for some viruses in that family; bold, potential vaccine solutions for the entire family; shaded box, viral families chosen for prototype pathogen selection.

Figure 3.

Common gaps along the research and development continuum that inhibit the development of medical countermeasures. Subject matter experts identified several research gaps within the 10 viral families of pandemic concern that were common among all the families. Addressing the challenges and closing those gaps will advance the development of medical countermeasures.