Reverse development of vaccines against antimicrobial-resistant pathogens

Area of Science:

• Vaccinology and Infectious Diseases
• Clinical Trial Design
• Immunological Correlates of Protection

Background:

• Traditional vaccine research and development (R&D) is a lengthy process, often exceeding 10 years.
• Vaccine candidates frequently fail in clinical development due to unreliable animal models or the absence of established immunological correlates of protection.
• Lack of a correlate of protection hinders the prediction of phase-3 efficacy from early-phase safety and immunogenicity studies.

Purpose of the Study:

• To introduce and advocate for Reverse Vaccine Development (RVD) as a novel approach for vaccines targeting antimicrobial-resistant (AMR) pathogens.
• To enable early proof-of-principle efficacy evaluation in populations with high disease incidence, such as controlled human infection models.
• To identify correlates of protection early in the clinical development process.

Main Methods:

• RVD evaluates proof-of-principle efficacy in populations with high disease incidence, potentially differing from the target registration population.
• Controlled human infection models can be utilized for early efficacy assessment.
• Compares vaccine-elicited immune responses between protected and unprotected subjects to identify correlates of protection.

Main Results:

• Identification of a correlate of protection allows for refinement of vaccine dosage, schedule, and formulation.
• Facilitates the assessment of vaccine efficacy across diverse populations with varying attack rates and disease characteristics.
• RVD offers a viable pathway for developing vaccines against AMR pathogens, which often have low incidence rates unsuitable for traditional phase-3 trials.

Conclusions:

• Early identification of correlates of protection via RVD can prevent large-scale phase-3 trial failures and the use of inefficacious vaccines.
• This approach is crucial for overcoming disinvestment in vaccines against AMR pathogens.
• RVD holds the potential to accelerate the delivery of life-saving vaccines to populations most in need.