The next crop of COVID-19 vaccine developers takes a more traditional route

CHICAGO / BERLIN (Reuters) – The handful of drug makers dominating the global coronavirus vaccine rush are pushing the boundaries of vaccine technology. The next crop under development features more conventional and proven designs.

The world will need several different vaccines to fight the COVID-19 pandemic, given the enormous size of the global need, the variations in the effects on different populations and possible limits of effectiveness in the first harvest.

Many of the leading candidates currently in final testing are based on new, largely unproven technology platforms designed to produce vaccines rapidly.

They include messenger RNA (mRNA) technology used by Moderna Inc MRNA.O and Pfizer Inc PFE.N with partner BioNTech SE 22UAy.Fand inactivated cold virus platforms used by the University of Oxford / AstraZeneca Plc AZN.L, Johnson & Johnson JNJ.N and CanSino Biologics 6185.HK, whose vaccine has been approved for military use in China.

Merck & Co MRK.N in September it began testing a COVID-19 vaccine based on a weakened measles virus that carries the genes of the new coronavirus in the body to stimulate an immune response to the coronavirus.

Of these, only the technology offered by J&J and CanSino that use cold viruses as vectors to deliver genetic material of the coronavirus has ever produced a licensed vaccine for Ebola.

The next batch of candidates – with late-stage trial results expected in the first half of 2021 – are heavily biased towards approaches that have yielded successful vaccines.

Conventional methods include using a killed or inactivated version of the pathogen that causes a disease to provoke an immune response, such as those used to make vaccines against influenza, polio and rabies.

Even more common are protein-based vaccines that use purified pieces of the virus to stimulate an immune response. Vaccines against whooping cough or whooping cough and shingles use this approach.

The French drug manufacturer Sanofi SASY.PA is developing a protein-based COVID-19 vaccine that uses the same approach used for its Flublok seasonal flu vaccine. Sanofi plans to begin final testing in early December, with approval expected in the first half of 2021.

While Novavax Inc NVAX.O has not yet produced a licensed vaccine, is using similar purified protein technology, and plans to launch a late-stage US trial involving 30,000 volunteers at the end of November.

“These are more traditional approaches, so we can feel more comfortable that we have a lot of experience with them,” said Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia.

Offit also sees promise in some of the inactivated viral vaccines developed by Chinese researchers, including Sinopharm’s China National Biotec Group (CNBG), one of the few first-crop developers using a traditional technique.

Other second-wave developers are making vaccines based on virus-like particles (VLPs), which mimic the structure of the coronavirus but contain no genetic material from it.

VLP vaccines can be produced in a variety of different cell types, including mammalian, bacterial, insect, yeast, and plant cells. This approach was used to develop vaccines for hepatitis B and human papillomavirus.

Medicago of Quebec is testing a VLP COVID-19 vaccine grown in tobacco plants with support from tobacco company Philip Morris PM.N..

Medicago has yet to produce an approved vaccine, but has completed large-scale testing for a seasonal flu vaccine using this approach. It plans to begin interim trials of its COVID-19 vaccine next month and aims to produce up to 1 billion doses per year by 2023.

Others are looking into alternative delivery methods, such as the nasal spray vaccine developed by a team from Xiamen University, the University of Hong Kong and Beijing Wantai Biological Pharmacy Enterprise, which is based on a modified flu virus.

FUTURE CHALLENGES

The second crop, however, could run into problems in carrying out large studies if current leaders take their vaccines beyond the milestone in the coming months.

“If we get a super vaccine in December from company x, which is on the market, it will be difficult to recruit participants in other studies,” said Peter Kremsner of the University Hospital of Tübingen, Germany.

“Then everyone will say, if the vaccine exists, I will get vaccinated with this vaccine now. This will definitely prove to be a problem for recruiting,” added Kremsner, who is testing CureVac. CVAC.O COVID-19 mRNA vaccine in early clinical trials with support from the Bill & Melinda Gates Foundation.

On the other hand, it is easier and faster to demonstrate efficacy when the spread of the virus in the community is rampant, as is happening again in the United States, Europe and elsewhere, a potential benefit for companies starting vaccine trials on large scale in the near future.