Live rotavirus vaccine development
Although manufacturers of existing rotavirus vaccines can meet demand over the next few years, new vaccines and suppliers will be essential to keeping pace with the global market as it continues to grow. In addition to increasing available supply, new vaccines mean more competition, which will help make all of the rotavirus vaccines on the market more affordable.
PATH is helping to advance the development of several promising new, live rotavirus vaccines that could prove both affordable and effective in the developing world. We are collaborating with emerging-country vaccine manufacturers on clinical development, formulation, process development, and manufacturing. We are also ensuring compliance with national and World Health Organization (WHO) regulations, streamlining the development process, and helping these vaccines to become licensed more quickly and meet international standards of quality.
Since 2001, we have been part of a collaborative effort to develop and evaluate ROTAVAC® (also known as “116E”), which obtained licensure in India in early 2014. We began by supporting Bharat Biotech International, Ltd. in India to conduct initial development and early-stage clinical trials. This collaboration emerged from the Vaccine Action Program—a cooperative effort of the US and Indian governments—and drew on the seminal efforts of several leading experts in the rotavirus field, including Drs. M.K. Bhan, George Curlin, Roger Glass, and Harry Greenberg. In India, we drew on the expertise of the Department of Biotechnology (DBT) in the Ministry of Science and Technology, the Indian Institute of Science, the All India Institute of Medical Sciences, the National Institute of Immunology, and the Society for Applied Studies (SAS). In the United States, we relied on experts from the National Institutes of Health (NIH), the Centers for Disease Control and Prevention, and Stanford University.
DBT, Bharat Biotech, SAS, and PATH completed a Phase 3 efficacy study of ROTAVAC® in late 2013, which involved 6,799 infants enrolled across three sites in India. The trial data showed the vaccine to have an excellent safety and efficacy profile, indicating that ROTAVAC® significantly reduced severe rotavirus diarrhea by more than half—56 percent during the first year of life, with protection continuing into the second year of life. This compares favorably with the efficacy of globally available rotavirus vaccines in low-resource countries. Moreover, ROTAVAC® also showed impact against severe diarrhea of any cause.
Now that ROTAVAC® is licensed in India, we are working with Bharat Biotech to seek prequalification of the vaccine by WHO, which will make it eligible for purchase by United Nations procurement agencies and, critical for rotavirus vaccines, for funding its purchase by the GAVI Alliance. DBT, Bharat Biotech, and PATH are currently conducting an additional study of ROTAVAC® at SAS to gather data relevant to the prequalification application—specifically, whether the simultaneous administration of ROTAVAC® with routine vaccinations has any impact on the infants’ immune response to the vaccines, and to test the consistency of three independent production lots of the vaccine.
Bovine-human reassortant vaccine candidates
The bovine-human reassortant vaccine (BRV), constructed by NIH, is designed to protect against the four most common rotavirus disease strains, as well as two that are largely present in Asia and Africa. The BRV is licensed to several manufacturers, mostly based in emerging countries, for further development.
PATH is working in partnership with Serum Institute of India, Ltd. (SIIL) to conduct a Phase 3 efficacy trial of their oral BRV candidate, which launched in May 2014. The multicenter trial, which will last three years, is being conducted with a total of 7,500 infants at six study sites across India. PATH and SIIL also completed a range of activities to prepare for the Phase 3 trial, including assessing potential trial sites, conducting preparatory studies at several of the sites, and finalizing the manufacturing process and formulation of the vaccine.
If the trial is successful, SIIL plans to develop and register the vaccine for use in India first and then will also seek to have the vaccine prequalified by WHO. To support this application, SIIL and PATH will conduct another study in India, in parallel to the efficacy trial, with approximately 1,200 additional infants to examine whether the simultaneous administration of SIIL’s BRV with routine vaccinations will have any impact on the infants’ immune response to the routine vaccines, and confirm the consistency of three different production lots of the BRV candidate.
In addition, PATH has been directly supporting China National Biotec Group’s Wuhan Institute of Biological Products since 2007 to prepare for initial clinical trials of their oral BRV candidate.
We also support the emerging-country manufacturers actively developing the BRV through a shared technology platform that provides a host of technologies, training, methodologies, and material. It is designed to meet common needs among the manufacturers, providing high-level expertise, minimizing cost, sharing knowledge, and ultimately accelerating the pace of development. Our work on the shared technology platform has included collaborations with the following groups:
- American Type Culture Collection in Manassas, Virginia, provided the starting material cell banks (a qualified passage Vero cell line) that meet international standards as substrate for production of rotavirus vaccines.
- Aridis Pharmaceuticals in San Jose, California, developed liquid and spray-dried formulations of the BRV that have been offered to manufacturers as options for their formulations.
- Charles River Laboratories International, Inc., headquartered in Wilmington, Massachusetts, completed testing of banks and seeds of manufacturers.
- Christian Medical College, Vellore in India prepared material and methods for the clinical assays and shared them with manufacturers.
- IDT-Biologika in Germany evaluated two production processes for the BRV and made the data and know-how available to manufacturers.
- Murdoch Children’s Research Institute in Australia produced, qualified, and shared assays and reagents for the titration and neutralization of the BRV.
- NIH constructed the BRV, trained manufacturers in the titration of the vaccine, and continues to play an advisory role in the vaccine’s development.
Vaccine development portfolio snapshot
- A Comprehensive Approach to Rotavirus Vaccines fact sheet
- DefeatDD website
- Health/WASH Network web page
- PATH Rotavirus Vaccine Access and Delivery website
- PATH Vaccine Resource Library: Rotavirus
- Rotavirus Vaccine Solutions fact sheet