If successful, this study could lead to World Health Organization approval
Researchers at the University of Maryland School of Medicine (UMSOM)’s Center for Vaccine Development & Global Health (CVD) are leading a study to evaluate the use of a pentavalent – or five in one – meningococcal conjugate vaccine (NmCV-5) among infants and young children in the meningitis belt of sub-Saharan Africa. This is the final and pivotal study for World Health Organization (WHO) prequalification of this vaccine, which is the last stage to make the vaccine available for low- and middle-income countries.
The study is part of the Infectious Diseases Clinical Research Consortium (IDCRC), a clinical trials network established by the National Institute of Allergy and Infectious Diseases in 2019. UMSOM’s Vaccine Treatment and Evaluation Unit (VTEU) is performing the study in partnership with the Center for Vaccine Development-Mali (CVD-Mali). The international global health organization PATH is providing support for study design, and it is managing and funding the serology testing. Serum Institute of India is providing study vaccines and technical support for study design.
Meningococcal meningitis, caused by invasive strains of Neisseria meningitidis, is a major public health concern because of its considerable morbidity and mortality, including high rates of death and permanent disability, in sub-Saharan Africa. Case fatality during meningococcal meningitis epidemics can surpass 15 percent, and rates of long-term complications among meningitis survivors in Africa are twice as high as in high-income countries. Because of the rapid onset of invasive bacterial meningitis and difficulties in access to care in the African meningitis belt, prevention by vaccination is the optimal way to reduce meningitis cases.
“I believe this work has a vitally important role to play in the development of safe and effective prevention strategies for meningitis in sub-Saharan Africa. As the world continues to focus on COVID-19, it is paramount that we do not forget the long-standing diseases that continue to have such a devastating effect on communities throughout the region,” said Samba Sow, MD, MS, director general of the CVD-Mali and Adjunct Professor of Medicine at the UMSOM. “Meningococcal meningitis is deadly, and the long-term effects for survivors can be debilitating. This new vaccine could offer real hope of drastically reducing the burden of meningitis and freeing entire populations from a disease that prevents them from living full and active lives.”
Study participants will include infants randomized to receive a meningococcal vaccine at 9 months or 15 months. Infants randomized to the 9-month age group will be further randomized in a 2:1 ratio to receive a single dose of the experimental meningococcal vaccine (NmCV-5) or a single dose of the comparator meningococcal vaccine (MenACWY-TT, Nimenrix). Infants randomized to the 15-month age group will be randomized in a 2:1 ratio to receive a single dose of NmCV-5 or a single dose of MenACWY-TT.
If results from the study are encouraging and the vaccine subsequently gets WHO approval, it could lead to a monumental shift in the burden of meningitis felt acutely in susceptible parts of Africa.
“I am excited to lead this critical clinical study of a vaccine that has the potential to virtually eradicate invasive meningococcal disease from the meningitis belt,” said Wilbur Chen, MD, MS, Professor of Medicine at UMSOM’s Center for Vaccine Development and Global Health (CVD) and protocol chair for this study.
NmCV–5 is designed to protect against the following meningitis types – A, C, W, X, and Y – all epidemic-causing strains currently circulating in the African meningitis belt. The vaccine is heat stable at 40 degrees (Celsius), and it will be affordable for African countries. It will be the only vaccine offering protection against the X meningitis strain. It already has been found safe and immunogenic for people ages 1 to 29 in Africa. The vaccine is developed by the Serum Institute of India Pvt. Ltd. in partnership with PATH.
“NmCV-5 is a groundbreaking vaccine that has the potential to end meningococcal disease epidemics in the African meningitis belt for good. To fully realize that potential, we must ensure it is available for routine use in young children and infants. This study will help expand the evidence base for NmCV-5 and advance access to a vaccine that could prevent tens of thousands of cases of meningitis and save thousands of lives every year,” said Mark Alderson, PhD, bacterial vaccines initiative leader at PATH.
Karen Kotloff, MD, Professor of Pediatrics, Associate Director for Clinical Research of UMSOM’s CVD, and principal investigator of the UMSOM VTEU, commented: “This collaboration among global partners toward the development of a safe, effective and inexpensive vaccine brings us one giant step closer to eliminating the devastating epidemics of meningococcal meningitis in sub-Saharan Africa.”
Rajeev Dhere, PhD, Executive Director at the Serum Institute of India Pvt Ltd., added that the vaccine is the “world’s first pentavalent meningococcal conjugate vaccine containing serogroup X.” He said that after “widespread use of MenAfrivac, meningococcal A disease has been virtually eliminated from the African meningitis belt.” Similarly, NmCV-5 has the “potential to end meningococcal disease epidemics caused by other predominant serogroups,” Dhere said.
As levels of COVID-19 fall around the world, UMSOM is pivoting not only to continue important COVID-19 vaccine and treatment research, but also to simultaneously study other critical vaccines. “The University of Maryland School of Medicine has been at the forefront of research on diseases that are devastating for those affected in low- and middle-income countries,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean at UMSOM. “This study is an example of our efforts to work with partners, such as CVD Mali, to address the critical need to prevent meningitis when possible.”
Visit ClinicalTrials.gov for additional details. The IDCRC, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health, is conducting this study. The research is supported by NIAID cooperative agreement UM1AI148689.
About the University of Maryland School of Medicine
Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu
About Infectious Disease Clinical Research Consortium (IDCRC)
This activity is supported by the Infectious Diseases Clinical Research Consortium (IDCRC) through the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI148684). The IDCRC, consisting of the Vaccine Treatment and Evaluation Units (VTEUs) and the IDCRC Leadership Group, was formed in 2019 to support the planning and implementation of infectious diseases clinical research that efficiently addresses the scientific priorities of NIAID. The consortium includes infectious diseases leaders and clinical researchers from Emory University, University of Maryland School of Medicine, Baylor College of Medicine, Cincinnati Children’s Medical Center and University of Cincinnati, FHI360, Fred Hutchinson Cancer Research Center, Johns Hopkins University, Kaiser Permanente Washington Health Research Institute, New York University, Saint Louis University, Vanderbilt University Medical Center, University of Alabama at Birmingham, University of Rochester, University of Washington, and NIAID. For more information about the IDCRC, please visit www.IDCRC.org.
About the University of Maryland School of Medicine Vaccine Treatment and Evaluation Unit (VTEU)
NIAID established the Vaccine and Treatment Evaluation Units (VTEUs) in 1962 as a consortium comprising centers of excellence for conducting clinical trials to develop new and improved vaccines and therapies against infectious diseases. University of Maryland School of Medicine (UMSOM) investigators have been the recipients of this award for over four decades (current award number 5UM1AI148689) and have conducted hundreds of clinical trials to develop products that can be used to reduce disease burden and to counteract existing and emerging public health threats. In keeping with our focus on bringing vaccines to underserved populations globally, we perform international studies of vaccines to prevent the major killers of children in the world, including malaria, meningitis, diarrheal disease, and pneumonia. With its rapid response capability, the VTEU at UMSOM plays leadership roles in pivotal trials that support approval and licensure of vaccines and therapeutics to control pandemics including the 2009 swine flu and COVID-19. Other trials have strengthened the national stockpile of vaccines to prevent infections that could be used as a bioterrorist weapon against the U.S., such as smallpox and anthrax. Innovative strategies are used to expand the array of pathogens that can be prevented with vaccines, and to improve delivery, strengthen effectiveness, and expand supply and access to these life-saving measures. The VTEU at UMSOM conducted the first clinical study of an edible vaccine that that might protect against travelers’ diarrhea, evaluated numerous needle-free vaccine administration strategies, developed combination vaccines so fewer inoculations could prevent more infections, and tested a topical antibiotic to prevent serious infections among critically ill infants. The broad opportunities provided by the VTEU has contributed to the training of generations of vaccinologists.