There are many coronavirus vaccines under development globally, however, more than two thirds rely on new or experimental unproven technologies with no track record of scalability, affordability or proven safety and efficacy in humans.
Texas Children’s Hospital Center for Vaccine Development (TCHCVD) at Baylor College of Medicine is a product development partnership that has been developing vaccines to prevent neglected and emerging infections for the past 20 years. We have successfully advanced new vaccines from discovery to clinical trials. TCHCVD is the anchor for translational medicine in the Texas Medical Center.
CoV RBD219-N1 Vaccine
Beginning in 2011, we embarked on efforts to develop coronavirus vaccines becoming one of the first major groups to recognize the pandemic threats caused by coronaviruses. We teamed with a leading coronavirus research group at the New York Blood Center now headed by Lanying Du, together with Dr. Kent Tseng from University of Texas Medical Branch. On that basis, we developed two recombinant subunit vaccines for the coronaviruses that caused both SARS and MERS outbreaks. The subunit vaccine for SARS, the SARS-CoV RBD219-N1 vaccine candidate, was technology transferred to WRAIR for its manufacturing under good practices and a batch of clinical-grade drug substance was generated. The intention is that the SARS-CoV RBD219-N1 vaccine candidate will be concurrently developed as a potential heterologous vaccine for SARS-COV-2.
This is because 1) SARS-CoV RBD is an immunogen of high quality; 2) SARS-CoV RBD is shovel ready for clinical studies; 3) this immunogen can be a comparator for cross-reaction/cross-protection/cross-neutralization evaluation of the SARS-COV-2 vaccine; and 4) this immunogen will be an important benchmark for evolution of SARS-CoV-2 and establish what might be expected from a mis-matched SARS-CoV-2 vaccine as “drift” accumulates during global spread and return of SARS-CoV-2 in “season 2” of the pandemic. Therefore, the parallel development of SARS-CoV RBD219-N1 is poised to accelerate and likely leapfrog the SARS-CoV-2 RBD-based vaccine program presented in this application. The comparative advantages of the SARS-CoV RBD219-N1 include:
1. Developed a low-cost and affordable vaccine process, which can be scaled globally by using a proven vaccine technology, which is now widely used globally to produce a hepatitis B vaccine administered to millions of people annually.
2. Robust preclinical data developed over a period of decade with careful attention to ensure the vaccine avoids eosinophilic cellular immunopathology (CIP) and/or antibody-dependent enhancement (ADE) noted to occur following challenge infections after immunizations with whole SARS/MERS virus vaccines, virus vectored vaccines, or even complete spike-protein vaccines. None of the vaccines currently advancing into human trials have undergone a robust preclinical animal study assessment. Emerging evidence indicates that these phenomena, including CIP linked to infiltration of host tissue eosinophils occur through induction of Th17 responses, while ADE can be prevented by removing epitopes located in the S-protein outside of the RBD component.
3. Created an alliance with Seattle-based product development partnership PATH to shape a regulatory and global access strategy. PATH previously led the development and introduction of the meningococcal A and malaria vaccines for Africa.
4. We have created a detailed communication strategy of every step in our approach by publishing a variety of peer-reviewed articles. View articles.
CoV RBD 2nd Generation Vaccines
Our goal is to accelerate the development of a safe and effective vaccine against COVID-19 using a well-known vaccine technology with a robust track record. Leveraging a decade of robust scientific evidence developing the receptor-binding domain (RBD) vaccines against SARS-CoV or MERS-CoV as safe and effective, we propose to implement our successful strategy and transition in an accelerated manner a SARS-CoV-2 RBD protein as a COVID-19 vaccine through the critical path of preclinical development leading to a rapid start of a first in human clinical trial.
The SARS-CoV-2 RBD protein-based COVID-19 vaccine will be developed in a record timeframe (18 months) for its immediate deployment into a first in human clinical trial. The RBDs of the SARS CoV2 and SARS CoV RBD219-N1 share high amino acid sequence similarity (>75% identity, >80% homology) and there is evidence that both viruses use the human ACE2 receptor for cell entry. Through a modest NIH bridge funding (R01AI098775) we have already initiated the cloning selection activities. With this grant, however, we will only be able to identify the suitable RBD-expressing clone for SARS CoV2, but would not allow us to advance to process development and create a real vaccine product. However, this ongoing work already has given us a head-start and gives us added advantage to perform the activities under this proposal. To date, we already identified a suitable SARS-CoV-2 RBD construct that promises high-yield production of the vaccine antigen. Initial results confirm that the protein can be produced in yeast similar to SARS-CoV RBD and we predict we can use a process similar to the one developed for the SARS-CoV RBD vaccine antigen.
The accelerated development, therefore, is based on:
- Similar strategy for genetic engineering and cloning between SARS-CoV RBD and SARS-CoV-2 RBD
- Similar strategy for process development and optimization
- Prior evidence of the ability to develop a robust and reproducible process
- Adaptable assays that can be repurposed for quality control and stability testing
- Similar strategy for buffer and adjuvant development and evaluation
- Preliminary evidence of binding, antigenicity and immunogenicity of SARS-CoV-2 RBD
- Rapid development and testing using parallel approaches to determine protective efficacy
- Prior success at transferring the production technology to WRAIR
- Prior evidence of initial of preclinical safety the SARS-CoV RBD vaccine
- A group of highly qualified scientific and program management teams that will ensure a successful integrated product development strategy and achieve all milestones and timelines