WHO mapping out COVID-19 vaccines
WHO is creating a roadmap to develop COVID-19 vaccines
Scientists from biopharma companies, universities and regulatory agencies met at the WHO Feb. 11-12 to draw a roadmap for the development of vaccines to protect against COVID-19 amid a rapidly shifting terrain.
While knowledge about the disease is limited and changing daily, vaccine development is moving at an unprecedented pace. Priorities out of the WHO meeting include drafting a target product profile (TPP), designing a master protocol to test multiple vaccine candidates in parallel, and coordinating international work on animal models and standards, scientists who attended the meeting told BioCentury (see "Designing a Master Protocol for 2019-nCoV Outbreak").
The meeting, which considered a range of R&D issues in addition to vaccine development, was co-sponsored by WHO and the Global Research Collaboration for Infectious Disease Preparedness (GloPID-R). The vaccine working group was chaired by Philip Krause, deputy director of the Office of Vaccines Research and Review at FDA’s Center for Drug Evaluation and Research.
There was a lot of debate about the preclinical work that must be done to support a Phase I study.
“Usually it takes two years to design and conduct multiple animal studies to assess toxicity and immunogenicity. That’s being compressed into weeks," Gregory Glenn, president for R&D at Novavax Inc. (NASDAQ:NVAX), told BioCentury. “We probably need to have some standardized assays so that everybody is using the same measuring stick for claims” about their vaccine candidates.
“There’s a consensus on the path forward, and the consensus is also that a lot of work needs to be done to get us there.”
“There's a consensus on the path forward, and the consensus is also that a lot of work needs to be done to get us there,” Johan Van Hoof, global therapeutic area head for infectious diseases and vaccines at the Janssen unit of Johnson & Johnson, told BioCentury.
That work includes validating animal models to assess vaccine immunogenicity, efficacy and safety, and developing standardized reagents to evaluate vaccines.
“We need to induce robust immune responses, both functional neutralizing antibodies and ideally also cell-mediated immunity,” Van Hoof said. “Those are the minimal requirements to have a protective vaccine.”
Experience with related coronaviruses like severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) will speed up the process.
“The good news is that we don't have to start from scratch,” Van Hoof said. “There is some similarity with the SARS virus and the animal models that have been developed” provide a starting point for COVID-19.
Defining a target product profile
Defining a TPP will help funders decide which vaccine candidates should be tested in the field if the outbreak is active when they are ready for large-scale clinical trials.
“We have to make big decisions now about the best candidate vaccines, and they are going to require huge investments,” Michael Ryan, executive director of the WHO Health Emergencies Program, told reporters on Feb. 12.
He noted that advancing a vaccine into Phase III trials “requires hundreds of millions of dollars to be invested and we may have to invest in multiple candidates without any certainty that one of them will work.”
Decisions about which vaccine candidates should be tested will “not be made just by the private sector,” Ryan said. “The state sector is going to have to get involved to stimulate [R&D] and take some of the risk with the private sector to advance those potential candidates.”
There was debate at the WHO meeting about the definition of a TPP that will inform clinical trial design as well as go- no-go decisions on candidate vaccines.
“We need a general TPP from the WHO that we can work with,” Lidia Oostvogels, VP area head for infectious diseases at CureVac AG, told BioCentury.
“Prevention of infection would be a beautiful goal, but when we know so little about the disease, I don’t know if we can obtain it,” said Oostvogels, who added that preventing severe disease and clinical symptoms is a more realistic goal.
CureVac hopes to start a Phase I study in June or July of a COVID-19 candidate vaccine based on the company’s mRNA technology. The company has sufficient funding from the Coalition for Epidemic Preparedness Innovations (CEPI), a public-private partnership, to bring a vaccine candidate through Phase I trials.
“There was complete agreement that we're not trying to prevent infection and we shouldn't expect that," said Glenn, who went even further, arguing that complete protection against disease symptoms is not necessary. “If you could decrease hospitalizations by 70%, that would be a massive, massive improvement.”
“Prevention of infection would be a beautiful goal, but when we know so little about the disease, I don’t know if we can obtain it.”
The meeting did not lay out a timeline for defining a TPP. Janssen's Van Hoof told BioCentury it would be “difficult and potentially risky” to produce a definitive TPP right now, as it risks “discouraging some candidates that at the end of the day would be good solutions.”
He noted that vaccine characteristics should be defined in the context of scientific feasibility, citing temperature stability and the number of doses administered as critical considerations.
“People would probably all want to have a single-dose vaccine that can be maintained at room temperature, and in some parts of the world room temperature represents a very high temperature,” Van Hoof said. On the other hand, “everyone would be very happy if you have a highly efficacious vaccine, even if two doses are needed.”
He added that it will be important to produce sustained immune responses that provide long-term protection. “History has taught -- certainly for organisms for which the organism never has been primed before -- that multiple doses are needed.”
At least 37 companies and academic groups, including 25 in China, have announced COVID-19 vaccine development programs (see Table: "COVID-19 Vaccine Development Programs").
Janssen told BioCentury it hopes to start a Phase I clinical study of a COVID-19 vaccine candidate within approximately 8-12 months. It is using the same recombinant adenovirus (rAdV) vector platform that was the basis for an investigational Ebola vaccine that is being administered in the Democratic Republic of the Congo and Rwanda, and for several investigational vaccines that are under development.
Janssen has created seven constructs and has started testing them in mice, Van Hoof said.
Moderna Inc. (NASDAQ:MRNA) is preparing its mRNA-1273 mRNA COVID-19 for a Phase I trial that its collaborator, NIH’s National Institute for Allergy and Infectious Diseases, will conduct. CEPI has provided funding through Phase I.
The first clinical batch of mRNA-1273, including fill and finishing of vials, was completed on February 7, Moderna told BioCentury. “This mRNA vaccine was designed and manufactured in 25 days and is undergoing analytical testing prior to release to the NIH for use in their planned Phase I clinical trial in the U.S.”
The prospects for Codagenix Inc. to bring a COVID-19 vaccine to market were boosted last week by its announcement of a collaboration with the Serum Institute of India Pvt. Ltd. to co-develop a live attenuated vaccine.
The Serum Institute, one of the world’s largest manufacturers of vaccines, will provide milestone-based funding of preclinical and clinical development, Codagenix CEO J. Robert Coleman told BioCentury.
If Codagenix develops a successful vaccine, the Serum Institute has committed to manufacture it, Coleman said.
Codagenix is developing a COVID-19 vaccine using its computationally designed live attenuated virus technology.
Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine is working on two candidate vaccines for COVID-19. One is a SARS vaccine candidate “which is predicted to confer cross-protection against” COVID-19, Maria Elena Bottazzi, co-director of the Texas Children’s Hospital Center for Vaccine Development - Product Development Partnership (PDP), told BioCentury.
The SARS vaccine “has completed cGMP manufacturing and could move into clinical trials quickly,” said Peter Hotez, co-director of the Texas Children’s PDP and dean of the National School of Tropical Medicine. The team is seeking partners and funding for both programs.
The vaccines minimize or prevent antibody-dependent enhancement (ADE), a “problem for many respiratory virus vaccines, in which the vaccine can cause a paradoxical worsening after virus infection,” Hotez said. "ADE also occurs with some virus constructs of SARS and is therefore a potential safety problem with coronavirus vaccines.”
Vaxart Inc. (NasdaqGS:VXRT) is developing an oral recombinant COVID-19 vaccine that would be administered by tablet.
Like the company’s other investigational vaccines, its COVID-19 vaccine uses an adenovirus type 5 (Ad5) vector to carry genes coding for an antigen and an adjuvant to the mucosa of the small intestine, Vaxart CEO and chairman Wouter Latour told BioCentury.
Vaxart’s vaccines differentiate themselves by providing a “really robust mucosal response” that could be particularly important for a disease like COVID-19 that affects the respiratory system, Latour said. Vaxart will need external funding or collaboration to bring its vaccine past preclinical studies, he said.
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