With unprecedented vaccine disparities materializing worldwide in response to the COVID-19 pandemic, a new promising economical vaccine now entering clinical trials holds great promise for low-and middle-income countries (LMICs). Called NDV-HXP-S and developed inside of eggs—much like the influenza vaccine—this vaccine can be stored at 2-8 Celsius (35.6 to 42.8F), making this COVID-19 vaccine candidate far easier to store and distribute around the world. Using what University of Texas at Austin, one of the vaccine’s developers, calls “a highly stabilized spike protein from the surface of the coronavirus in order to train the human immune system to recognize and fight infection.” The investigational product known as “HexaPro” was developed at three different UT faculty laboratories in partnership with Icahn School of Medicine at Mount Sinai in New York and global partners, including PATH concerned about ensuring that the poorest parts of the world have access to high quality COVID-19 vaccines. Now the experimental vaccine makes it way into clinical trials in Vietnam and Thailand with plans for Brazil.
TrialSite offers a brief breakdown of this promising investigational vaccine.
Vaccine Candidate Origins
Thanks to a collaboration in early 2020 between UT Austin’s Jason McLellan, associate professor of molecular biosciences and a team at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center the group produced a design version of the SARS-CoV-2 spike protein that is stabilized to help the body recognize the threat from this pathogen as reported in a UT News entry. The results of this early work were published in Science.
Importantly, in nature, the COVID-19 pathogen’s spike protein is dynamic, changing its shape which makes detection more difficult hence back in early 2020 the research team exploited two mutations to hold the protein in its shape. Notably, the 2020 version of the spike protein is the basis for all of the vaccines approved for distribution in the United States, reports UT News.
The team leveraged the early success and designed HexaPro, an even greater stabilized version of this protein including six mutations that serve to stabilize the product, which according to UT News, leads to the production of more spike proteins to help the body fight COVID-19.
Jason McLellan, the co-developer of HexaPro, reports, “My team and I are thrilled that our second-generation stabilized spike protein is part of this vaccine.” The research team made six key modifications known as prolines which help lock the protein into the prefusion shape.
Mount Sinai Contribution
Working in collaboration with the UT Austin team, Peter Palese, the Horace Goldsmith professor and chair of microbiology and professor of medicine at Icahn School of Medicine at Mount Sinai, along with Adolfo Garcia-Sastre and Florian Krammer, genetically engineered a virus called Newcastle Disease Virus to help the body recognize the spike protein from the Texas team.
NDV-HXP-S (named for both the Newcastle Disease Virus and HexaPro) is produced using the same method that has been used for influenza vaccines since the 1950s, which is faster, cheaper, and less complicated than the methods used to produce several leading COVID-19 vaccines. The vaccine is also stable at regular refrigerator temperatures (2-8 degrees Celsius) for weeks, a much higher temperature than needed for leading mRNA COVID-19 vaccines.
Pandemic Exposes Health Inequities
“We are witnessing unprecedented disparities in COVID-19 vaccine access around the world,” said Ilya Finkelstein, an associate professor in the Department of Molecular Biosciences, a collaborator on the technology. “We designed HexaPro to be a more stable antigen. In cell culture, this translated to a more than tenfold increased yield relative to the first-generation spike constructs used in current vaccines. If this holds for NDV-HXP-S, HexaPro will bring us a step closer towards addressing the wide disparity in vaccine access.”
Recently a study was uploaded to clinicaltrials.gov involving NDV-HXP-S. Sponsored by Mahidol University in Thailand, the 210 participant study is conducted in two phases. Phase 1 is designed for the study team and sponsor to evaluate the safety, tolerability and immunogenicity of the vaccine administered at different dose levels (1, 3 and 10 µg) without adjuvant, and at two different levels (1 and 3 µg) with the adjuvant CpG 1018 among healthy adults aged 18 to 59.
The study participants receive two doses of assigned investigational product (IP) on day 1 and day 29 and thereafter are assessed in the clinic for safety and reactogenicity at 7 days after each jab. After an interim analysis of Phase 1 data is completed and data merits, the study team commences Phase 2, which involves 250 participants, including one third of them aged 60 to 75 years.
Commercialization for LMICs Access
An organization known as PATH approached both Mount Sinai and UT Austin to license the intellectual property in order to provide access to the vaccine to manufacturers in each of three nations, including the following:
- Vietnam’s Institute of Vaccines and Medical Biologicals (IVAC)
- Thailand’s Government Pharmaceutical Organization (GPO)
- Brazil’s Butantan Institute
Who is PATH?
PATH used to be known as Program for Appropriate Technology in health and is an international nonprofit global health organization based in Seattle, Washington. With 1,600 employees in over 70+ officers around the word, their official tagline is “Better health moves humanity forward.”
Launched back in 1977 with an emphasis on family planning, the nonprofit expanded its efforts into areas involving maternal health, child health, reproductive health vaccines and immunization and emerging epidemic diseases from HIV and malaria to TB. One of the largest nonprofit organizations in global health today, they employ about 1,600 working in over 70 countries with a budget of $305 million according to a Wikipedia entry. PATH collaborates with biopharma companies to support the development of vaccines for conditions such as meningitis, pneumonia and helps countries introduce vaccines for childhood disease such as rotavirus and Japanese encephalitis.
PATH has encountered controversy: for example, back in 2013 when it was alleged to be involved with “malpractices” involving a vaccination program in India—the report can be read here. It involved the deaths of some Tribal girls in Andhra Pardesh during a program involving Gardasil vaccination testing. The government of India stopped further testing and issued a pardon.
The Intellectual Property
The U.S. patent application was filed for HexaPro and included the following inventors: Ching-Lin Hsieh, Jory A. Goldsmith, Jeffrey M. Schaub, Chia-Wei Chou, Andrea M. DiVenere, Kamyab Javanmardi, Hung-Che Kuo, Daniel Wrapp, Patrick O. Byrne, Christy K. Hjorth, Nicole V. Johnson, Nianshuang Wang, Jennifer A. Maynard, Ilya J. Finkelstein and Jason S. McLellan.
Note that the inventors stand to possibly benefit, should the trials be successful and the vaccine approved in targeted countries.
Call to Action: TrialSite will monitor the study ongoing.