Gene-based strategies hasten COVID-19 vaccine development

August 12, 2020 0 By FM

While cautioning that data from a safety trial is no guarantee that the vaccine will work in protecting an individual from infection, vaccinologists are excited to see multiple, innovative strategies in play to bring about an effective vaccine.  

Four of the vaccine developers –Oxford-AstraZeneca, Moderna-NIAID, Pfizer-BioNTech, and CanSino — have already presented safety data of their experimental vaccines on humans and entered late phase clinical trials.

Both Oxford and CanSino, a Chinese firm, exploited the adenovirus vector platform to develop their vaccines. The technology involves altering the genes of the adenovirus, another common virus, to induce an immune response.

The adenovirus used in the Oxford vaccine is found in chimpanzees. Humans do not have pre existing antibodies against it. 

The chimpanzee cold-causing adenovirus, which is safe in humans, is engineered to express the spike protein — the major surface protein the virus uses to bind the host cell — of the SARS-CoV-2 virus as a way of tricking the immune system. 

The Oxford team has experience in using the technology while working on the Middle East Respiratory Syndrome or MERS — another coronavirus-caused pneumonia. MERS first emerged in 2012 in Saudi Arabia, and threatened to cause a global health crisis. But an outbreak didn’t occur until 2014. The spike protein of MERS shares 40% to 50% similarity to the spike protein of SARS-CoV-2, researchers said.

Data from a small safety trial published in April this year showed that the vaccine was safe and elicited an immune response that persisted for a year. It produced high levels of T-cells, but only 44% of the people receiving the highest dose generated neutralising antibodies. That indicates that one dose of the vaccine may be not adequate to achieve the required antibody levels.

The small trial was inconclusive in proving whether the combination of T-cells and neutralizing antibodies induced by the vaccine worked to prevent the disease.

The CanSino vaccine, on the other hand, utilises a widespread adenovirus that causes the common cold in humans. Some researchers fear there is a likelihood of existing antibodies against that adenovirus neutralising the effect of the vaccine.

The vaccine, which is tested in a trial of about 500 participants in China, appeared least likely to be effective, based on the early results released so far, scientists said.  

The other two, Pfizer-BioNTech and Moderna vaccines, use the mRNA technology platform. The BioNTech candidate contains RNA instructions for the ‘receptor binding domain’ portion of the coronavirus’ spike protein, whereas the competing Moderna RNA vaccine is made of the entire spike protein. 

Preliminary results released by the joint venture between Pfizer and the German firm appeared able to produce a strong immune response based on a trial with 60 participants in Germany at various dosage levels.

Russia, India in the fray

Vaccines from countries, including Russia and India, are reportedly at advanced stages of clinical studies. 

Russia’s Sechenov University has reported the successful completion of tests on volunteers for a potential vaccine candidate. The country hopes to finish trials of a coronavirus vaccine in August and aims to produce 30 million doses with the help of international partners by the end of this year.

Human trials of Russia’s second potential coronavirus vaccine, developed by Siberian Vector Institute, are also reportedly underway.

Indian Council of Medical Research (ICMR), the top governing body of medical research in the country, announced in July that India’s indigenously developed inactivated COVID-19 vaccine candidate is undergoing phase 3 studies at various centres.

Besides, a plasmid DNA vaccine developed by the pharmaceutical firm Zydus Cadila received a regulatory nod to start human trials in India.

A major factor that enables researchers to cut short the development timelines is the use of the so-called gene-based (mRNA) technology. Currently, about a fifth of the COVID-19 vaccine projects rely on this technology. These experimental vaccines can be made more speedily than conventional ones, which contain an inactivated or weakened version of a pathogen, or a piece of it.

No gene-based vaccine, however, has yet been licensed for humans, although a few are in use in veterinary medicine.

Protein-based vaccines and whole virus vaccines are among other major approaches being explored by researchers, besides viral vector vaccines and genetic vaccines. 

“We’ve been committed to making the impossible possible by working tirelessly to develop and produce in record time a safe and effective vaccine to help bring an end to this global health crisis,” Dr Albert Bourla, Pfizer’s chairman and chief executive officer, said in a news release.