Currently licensed live oral rotavirus vaccines, RotaTeq and Rotarix, are effective in preventing severe diarrhea among children in developed and middle income countries, but are significantly less effective in the developing world. While the causal mechanisms for this lower efficacy have not been clearly defined, we hypothesize that multiple factors, such as high titers of pre-existing maternal antibody, breast feeding and interference by other flora and viruses in the gut, might play a role in reduced vaccine efficiency among children. Consequently, rotavirus remains a major killer among children in low-income countries of Africa and Asia. In addition, both vaccines are associated with a low risk of diarrhea and intussusception (i.e., blockage of the small intestine) 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 and protective efficacy in piglets of this IRV by intramuscular (IM) injection and transcutaneous administration using microneedles. With the establishment of proof of concept for parenteral (i.e., non-oral) immunization, CDC has licensed this technology to a number of vaccine manufacturers for further R&D and clinical development of an IM IRV.
We now propose a SBIR topic for the formulation and fabrication of a dissolving microneedle patch to deliver an IRV for transcutaneous immunization against rotavirus in collaboration with a contract manufacturing organization. We have recently demonstrated enhanced immunogenicity of our IRV using an innovative metal 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 with large volume of cold storage and high cost, a major advantage for immunization campaigns in the developing world.
Transcutaneous immunization using a dissolvable microneedle patch is a novel and innovative approach to the prevention against infectious diseases, but no such vaccines have been licensed for use in humans yet. Currently this technology to deliver influenza vaccine is being tested and evaluated in phase I clinical trials. Similar clinical trials for inactivated polio vaccine (IPV) using a dissolvable microneedle patch are being planned for the next few years. However, no development and proof of concept work have been done for IRV.
The goal of this project is to conduct formulation and process development and a feasibility study to manufacture a dissolving microneedle patch for skin immunization against rotavirus. This program area will provide small business companies with opportunities to apply for necessary funds and work with CDC scientists to further optimize the fabrication process and prepare a dissolving microneedle patch for clinical trials of a patch IRV.
Phase I Activities and Expected Deliverables
1. Develop an outline for the project goals described above.
2. Develop a draft scalable manufacturing process for a dissolving microneedle patch, including formulation and fabrication of IRV and necessary assays.
Expected Phase II Activities
1. Develop and validate a scalable manufacturing process for a dissolving microneedle patch.
2. Develop and implement manufacturing methods to make microneedle patches for IRV vaccination under good manufacturing practice (GMP) conditions.
3. Support regulatory approval to conduct a phase I clinical trial of IRV vaccination using a microneedle patch.
4. Support for a phase I clinical trial to assess the safety, immunogenicity, reactogenicity, and acceptability of IRV vaccination using a microneedle patch.
The findings from this SBIR research 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 advance CDC’s Global Immunization Winnable Battle that includes increasing Global Health Impact of rotavirus vaccination.
Demonstration of the feasibility for the manufacture of a dissolving microneedle patch for IRV will bode well for a serious investment and more expeditious and effective development of this new and innovative IRV for commercialization. This IRV would be more efficacious in resource-poor settings because of its parenteral administration. As the world is transitioning to IPV from oral polio vaccine (OPV), a combined IPV and IRV in the expanded program on immunization (EPI) would ultimately increase global health impact through large immunization campaigns and help save more lives.