Adapting Simon's Two-Stage Design for Efficient Screening of Filovirus Vaccines in Non-Human Primates

Area of Science:

• Virology
• Vaccinology
• Primate Models

Background:

• Cynomolgus macaques (Macaca fascicularis) are crucial for filovirus vaccine testing.
• Limited Biosafety Level 4 (BSL-4) resources and ethical considerations necessitate efficient non-human primate (NHP) usage.

Purpose of the Study:

• To adapt Simon's two-stage design for screening Ebola virus (EBOV) vaccine candidates in NHPs.
• To optimize resource allocation and minimize NHP use in preclinical vaccine evaluation.

Main Methods:

• Adapted Simon's two-stage design for NHP vaccine screening, involving Stage 1 (2-4 NHPs) and Stage 2 (4 NHPs).
• Defined advancement criteria based on NHP survival and protection across both stages.
• Screened 27 EBOV vaccine candidates across 43 regimens, varying dose, adjuvant, formulation, and schedule.

Main Results:

• An 80% efficacious vaccine had an 88.5% chance of advancing; a 40% efficacious vaccine had an 83% chance of rejection.
• Of 30 regimens tested in Stage 1, 15 were rejected, 9 withdrawn, and 6 advanced to Stage 2.
• All 6 regimens advanced from Stage 2 are progressing in the product development pipeline.

Conclusions:

• Simon's two-stage design effectively screens EBOV vaccine candidates, enhancing efficiency and reducing NHP numbers.
• This adaptable screening strategy shows potential for evaluating Sudan virus (SUDV) and Marburg virus (MARV) vaccine candidates.
• The methodology supported the development of EBOV vaccines approved by regulatory agencies in 2019.