Description:
Background: The currently licensed oral rotavirus vaccines Rotarix™ and Rotateq™ are effective in reducing cases of severe diarrhea among children in high and middle income countries, but are significantly less effective in low income countries. In addition, both vaccines are associated with a low risk of diarrhea and intussusception among infants who receive the first dose of vaccine. To improve the safety and efficacy of oral rotavirus vaccines, CDC scientists have developed a proprietary inactivated rotavirus vaccine (IRV) technology (new human strains and a novel method for rotavirus inactivation) and demonstrated the immunogenicity in mice and protective efficacy in piglets of this IRV by intramuscular (IM) administration.
CDC has demonstrated good immunogenicity of the IRV using an innovative microneedle patch technology, achieving comparable antibody titers with a 1/10th of the antigen dose compared to those induced by a full IM dose of vaccine. Microneedles provide a simple and painless method to administer vaccines without using hypodermic needles. They are inexpensive to manufacture and may not need the cold chain, a major advantage for immunization campaigns in the developing world. The findings from this study may allow us to enhance public health through the development of a low cost vaccine with an improved safety and efficacy profile and thus help achieve and sustain global immunization initiatives such as rotavirus vaccines. Project Goal: With the establishment of proof of concept for intramuscular and skin immunization in animals, the CDC has licensed the technology to a number of vaccine manufacturers in the US and emerging developing countries for scale-up and clinical development as a stand-alone IRV first and then a combined pediatric vaccine. However, phase 1 safety data in the country of origin (USA in this case) is a prerequisite for vaccine manufacturers in developing countries to receive approval from their national regulatory agencies for clinical trials of a new vaccine. To meet this requirement, the goal of this project is to propose several specific research areas of interest, (1) production of a Vero cell bank, (2) production of two rotavirus seed banks and, (3) preparation of two pilot vaccine lots under Good Manufacturing Practice (GMP) conditions in partnership with a contract manufacturing organization (CMO). Pilot lots will include the preparation of an injectable IM vaccine first and microneedle patches for skin immunization, if enough funding is available.
Impact: Availability of GMP materials and phase I safety data will provide the opportunity to move this project forward, working with partners, to jointly develop this new and innovative IRV for use in children throughout the world. In long term, this IRV can be combined with other pediatric vaccines, such as IPV. Due to the parenteral administration, IRV will be equally effective in all settings, help save more lives, and ultimately increase global health impact through large immunization campaigns.
