Human safety trials of a coronavirus vaccine began in Oxford on Thursday, with the first two of 800 healthy volunteers recruited for the study being injected with new vaccine, ChAdOx1 nCoV-19. This is the sixth coronavirus vaccine to enter the first phase of clinical trials, raising hopes of an antidote against the virus that continues to ravage the world.
The trial will study whether the new vaccine is safe and can generate strong immune responses against Sars-Cov-2, the virus that causes the coronavirus disease (Covid-19), and protect healthy people from infection.
The vaccine is made from a weakened version of a common cold adenovirus, ChAdOx1, which has been genetically modified to make it impossible for it to infect humans.
To develop the vaccine, researchers added genetic material to ChAdOx1 from the Sars-CoV-2 virus’ surface protein, spike glycoprotein (S), which leads the virus to bind to Ace2 receptors to enter human cells and cause an infection.
“This type of vaccine uses recombinant technology where you insert a gene for an important protein of the virus you want to build immunity to, into a weak virus that can safely infect human beings. Here it is the spike protein of Sars-CoV-2 by which it enters cells, into a weak adenovirus. The expectation is that the weak recombinant adenovirus infection will cause antibody development against Sars-CoV2 spike protein, thereby creating immunity,” said Dr Anurag Agrawal, director, Council of Scientific and Industrial Research-Institute of Genomics and Integrative Biology.
“The ChAdOx1 vaccine uses a modified adenovirus carrying the coronavirus spike protein like a Trojan horse to enter human cells. The cells start making and releasing spike proteins, and, bingo, the immune system responds,” said Dr T Jacob John, professor emeritus and former head of virology at Christian Medical College, Vellore, Tamil Nadu.
The vaccine is safe and well tolerated, but some people may report mild and temporary side effects, such as a sore arm at the injection site, headaches or fevers in the first couple of days after vaccination, said researchers. In the study, half the healthy volunteers, between 18 and 55 years old, will receive the Covid-19 vaccine, and half a control vaccine, which protects against meningitis.
“By vaccinating with ChAdOx1 nCoV-19, we are hoping to make the body recognise and develop an immune response to the spike protein that will help stop the Sar-CoV-2 virus from entering human cells and, therefore, prevent infection,” said researchers led by Prof Andrew Pollard, director of the Oxford Vaccine Group.
The ChAdOx1 vaccine platform has been used to produce vaccine candidates against many viruses, including those causing influenza, chikungunya, and zika. The Oxford group has used it to develop a vaccine against Middle-East Respiratory Syndrome (Mers) coronavirus, which showed promising results in clinical trials.
If the trials are a success, scientists hope to have one million doses ready by September, and to dramatically scale up manufacturing after that.
“Vaccines based on viral vectors offer a high level of protein expression, have long-term stability, and induce strong immune responses in humans, which make them highly effective,” said Dr NK Ganguly, former director general, Indian Council of Medical Research.
Vaccine development against Covid-19 has progressed at an unprecedented pace and scale, with 78 projects reaching the active stage of development since China shared the genetic sequence of Sars-CoV-2 with the World Health Organization on January 12, 2020, according to the Coalition of Epidemic Preparedness Innovations (Cepi), one of the world’s biggest public funders of vaccine development.
Like the Oxford Vaccine Group, most developers are leveraging existing work on vaccines against Mers and rapid response platforms with 2019-nCoV genetic sequences inserted to speed up vaccine development. The research focus is on platforms based on nucleotides, which are the building blocks of genetic material, DNA and RNA, because of their potential for speed and flexibility for antigen manipulation.
“The Oxford vaccine will be the third CEPI-funded vaccine to enter into phase 1 trials, along with Inovio’s INO-4800 DNA vaccine candidate and Moderna’s mRNA-1273 candidate… Producing a safe, effective, and globally accessible vaccine is our best hope in ending this pandemic. We aim to do this at a speed never before seen in vaccine development,” said Dr. Richard Hatchett, chief executive officer, Cepi, in a statement.
Cepi has initiated eight Covid-19 vaccine development projects with Curevac, Inovio Pharmaceuticals, Moderna, Novavax, University of Hong Kong, University of Queensland, and a consortium led by Institut Pasteur, with a goal of having at least three vaccine candidates submitted to regulatory authorities for licensure for general use.
“If an international vaccine trial is successful, its emergency use can be sanctioned globally. If a vaccine trial is well designed and successful anywhere in the world, it can be used as the virus is the same. Some other countries are more suitable for efficacy trials, but no regular trial approval is needed in India following emergency use approval,” said Dr Ganguly.
Vaccine development, on an average, takes 10.71 years from the preclinical phase, and has a market entry probability of 6%, according to a study in PLOS One, a peer reviewed scientific journal.
Adaptive and parallel vaccine development phases, innovative regulatory processes, and advanced scale up manufacturing capacity have helped fast-track development, which traditionally takes an average of a decade. Even accelerated efforts, such as that for the first Ebola vaccine, took five years.
Pune-based Serum Institute of India (SII) has partnered with the Oxford University to manufacture the vaccine in India. “SII plans to begin manufacturing the ChAdOx1 vaccine in anticipation of the clinical trials in the UK succeeding by September/October. SII will initiate the manufacture at its own risk to jump-start manufacturing and have enough doses available, if the clinical trials work,” said SII CEO Adar Poonawalla.
Our goal is a vaccine before 18 months. Normally, it takes about a decade to develop a vaccine, but global partnerships (between health agencies, academics, donors, industry, nations and philanthropies) have helped hasten development of vaccines against emerging public health threats. A vaccine against Ebola took five years, the one against zika took less than two years. The global effort to develop a Covid-19 vaccine in less than 18 months is unprecedented and would be an amazing achievement,” Dr Soumya Swaminathan, chief scientist, World Health Organisation, told HT on the phone from Geneva.
