CIDRAP and global health experts identify research priorities for Zika virus preparedness and response

In a series of four manuscripts published jointly by The Lancet Infectious Diseases and The Lancet Microbe, the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota, working with a network of global experts, identified key research priorities needed to detect and mitigate the threat of future mosquito-borne Zika virus outbreaks.

In 2015–2016, Zika virus emerged in the Americas and rapidly spread throughout the region and beyond, resulting in a devastating epidemic of infants born with small heads (microcephaly) and other severe congenital malformations. The World Health Organization declared the Zika epidemic a public health emergency of international concern in 2016. Despite this declaration, there remain no licensed Zika virus vaccines, therapeutics, or diagnostic tests that are appropriate for routine prenatal screening, leaving the world unprepared to respond to ongoing transmission and future epidemics.

The four manuscripts outline a priority research agenda for Zika, based on extensive literature reviews, input from an expert working group, and a meeting of 130 global leaders in Zika research and development that CIDRAP led with the Wellcome Trust in December 2023.

The four manuscripts focus on: Zika research priorities for preparedness and response, vaccines and monoclonal antibodies, non-human primate models, and sharing of specimens and data to accelerate Zika research and development.

Zika virus: advancing a priority research agenda for preparedness and response published in The Lancet Infectious Diseases

To address the critical lack of Zika virus vaccines, therapeutics, and diagnostics for routine screening, CIDRAP and global health experts reviewed key challenges and knowledge gaps in Zika research and developed a priority agenda for preparedness and response. Among the priorities:

• Developing accurate diagnostic tests is central to Zika virus research, epidemiology, prenatal screening, and clinical care. Improved serological assays are under investigation, including tests that are easy to use or can distinguish among co-circulating mosquito-borne viruses. Systematic, standardized evaluations of leading candidates will accelerate development of tests needed for use worldwide.
• Strengthening systems for global surveillance and laboratory capacity is critical to improve early detection and rapid response to future Zika virus outbreaks.
• Overcoming complacency and building investment in research and development for Zika medical countermeasures and vector (mosquito) control are essential now for global preparedness and response against future epidemics.

Zika virus vaccines and monoclonal antibodies: a priority agenda for research and development published in The Lancet Infectious Diseases

No licensed Zika vaccines or monoclonal antibodies (mAbs) are currently available, leaving the world’s populations, and particularly those who may become pregnant, unprotected from ongoing virus transmission, infection, and disease. Global health experts developed a research agenda to address key knowledge gaps and accelerate the development and licensure of Zika vaccines and mAbs for global use. This agenda includes:

• Evaluation of Zika virus vaccine safety and efficacy: Clinical trials have demonstrated that Zika virus vaccine candidates can induce a protective immune response and are well tolerated.
• Evaluation of mAbs for prophylactic (preventive) use: The development of mAbs with high potency at low doses and immune protection over several months represents a potentially important and practical strategy to protect vulnerable populations during an outbreak.
• Research during periods of increased Zika virus transmission: Close collaboration among public health officials, industry experts, researchers, and regulators will facilitate planning and rapid implementation of clinical trials during future Zika outbreaks.
• Research during periods of low Zika virus transmission: Key tools such as biomarkers of immune protection are needed to identify promising vaccine and mAb candidates for further development and regulatory review. 

Role of non-human primate models in accelerating research and developing countermeasures against Zika virus infection published in The Lancet Microbe

The 2015-2016 epidemic revealed the devastating effects of congenital Zika virus infection on fetal development, resulting in a wide spectrum of neurological, ophthalmological, and development abnormalities in infants born across the Americas, Asia, and Africa. Non-human primate models have become essential tools for Zika research to understand the pathogenesis of congenital brain injury and perinatal complications and for developing and testing medical countermeasures, such as vaccines, diagnostics, and therapeutics. This paper, which was developed with the input of global health experts, summarizes the current literature of non-human primate models of Zika infection, with a focus on infection in pregnancy, including impairment of fetal neurodevelopment, miscarriage, and stillbirth. Among the conclusions:

• Non-human primate research has served as the gold standard for understanding pathogenicity and immune response related to Zika virus infection in pregnancy, and it is foundational for testing the benefits of vaccines and other medical countermeasures on fetal protection.
• Non-human primate research represents a critical tool to advance research and development during periods of low transmission, including selection of new vaccines or antiviral agents to deploy in human trials during future outbreaks.
• Sustained investment will be essential to accelerate the development of medical countermeasures that can prevent congenital infections of Zika and other emerging viruses before future epidemics occur.

Specimen and data sharing to advance research and development on Zika virus published in The Lancet Microbe

For diseases with epidemic potential, specimen and data sharing is crucial for sustained research and development of medical countermeasures. In the case of Zika, although a global framework for specimen and data sharing to advance research and development is highly desirable, challenges related to legal, ethical, and intellectual property issues persist. In this paper, global health experts underscore several key points:

• Continual engagement of all Zika-endemic countries in specimen and data sharing is important to ensure early alerts of outbreaks and to improve the understanding of Zika pathogenesis so that effective medical countermeasures can be developed and deployed.
• Priorities for moving forward include securing sustainable funding for laboratory capacity for the diagnosis and surveillance of Zika and other arboviruses, investing in the development of biobanks in Zika-endemic countries, and strengthening country partnerships.
• Defining the type of specimens and data that should be collected and ensuring specimen and data quality by developing standardized protocols for collection, characterization, and archiving is also important.

“The Zika epidemic took a devastating toll in 2015 and 2016, but the world moved on after transmission waned, before research was completed to develop vaccines and effective diagnostic tests,” said Eve Lackritz, M.D., CIDRAP deputy director and lead of the series. “As with all infectious disease threats, the critical time to prepare for future epidemics is now, so we have the tools and capacity to respond immediately when the emergency occurs. This series outlines the scientific agenda needed to ensure our preparedness, and build the visibility and investment needed for this largely forgotten public health threat.”

About the Center for Infectious Disease Research and Policy
Part of the University of Minnesota's Research and Innovation Office, CIDRAP is a global leader in addressing public health preparedness and emerging infectious disease response. Founded in 2001, CIDRAP works to prevent illness and death from targeted infectious disease threats through research and the translation of scientific information into practical applications, policies and solutions.