The race to develop the first effective vaccine against COVID-19 involves an awfully crowded field, with 137 candidate vaccines in pre-clinical study worldwide and another 23 actually in development. But a leader seemed to emerge today with research published in the Lancet reporting promising results in a robust study by investigators at Oxford University in England.
The study began in April, with a sample group of 1,077 adults aged 18 to 55—an age group young enough to tolerate exposure to SARS-CoV2, the virus that causes COVID-19, with less risk of adverse effects than would be seen in older, more vulnerable adults. The group was divided more or less in half, with 543 participants receiving the experimental COVID-19 vaccine, and the other 534 serving as a control group, receiving an existing vaccine against meningococcal vaccine. (The investigators chose not to use an inert saline solution for the control group because both vaccines can cause side effects such as achiness, fever and fatigue. Saline would cause no such symptoms and would thus reveal which group was the control group and which was not.)
The vaccine uses a harmless-to-humans chimpanzee adenovirus as a delivery vector. That virus is modified to carry spike proteins from SARS-CoV-2—the component of the coronavirus that, in theory, should induce the sought-after immune response in humans. What the researchers were looking for were two kinds of immune reaction: humoral immunity, or the system-wide generation of antibodies against the virus; and cellular immunity, or the activation of immune system T-cells that attack human cells infected with the COVID-19 virus.
Oxford vaccine triggers immune response, trial findsA Covid-19 vaccine candidate developed by the Oxford University has safely prompted a protective immune response in hundreds of volunteers who got the shot in an early trial, preliminary findings published Monday in the journal Lancet said. The vaccine, ChAdOx1 nCoV-19 (also called AZD1222), designed by Oxford and developed by AstraZeneca, the Anglo-Swedish pharma major, triggered a dual immune response in people aged 18 to 55 that lasted at least two months.
The preliminary findings are from the placebo-controlled, phase-I trial held between April 23 and May 21, involving 1,077 participants. 543 were administered the vaccine ChAdOx1 nCoV-19, another 534 a control vaccine (to rule out placebo). Further, ten participants were given a booster shot of the ChAdOx1 nCoV-19 vaccine. All participants who received the vaccine developed spike-specific antibodies by day 28, an immune response similar to those who recover from Covid-19. Spikes are the spike proteins on the surface of the SARS-CoV-2 coronavirus that it uses to attach to human receptor cells. The ten who received a booster shot produced neutralizing antibodies (antibodies in higher titers). The vaccine also triggered T cells, a type of white blood cell that “remembers” and attacks the coronavirus.
Side effects including fever, headaches, muscle aches, and injection site reactions were observed in about 60% of patients; but all these were deemed mild or moderate and were resolved during the trial.
T-cells and antibodies: That the vaccine has induced antibodies and T cells are significant. T cells can stay in the body for a longer period in a dormant state, and can re-emerge to attack the virus in case of an infection.
The science behind the Oxford vaccine
Preliminary data from the phase I/II trial of the Covid-19 vaccine developed by Oxford University showed it was safe and prompted an immune response that lasted at least two months. More on that and India’s role in the eventual rollout of the vaccine in today’s Times Top10. Here, we delve deeper into the science behind the vaccine.
Oxford’s candidate, ChAdOx1 nCoV-19 (also called AZD1222), is a non-replicant viral vector vaccine. The vector (the carrier) is derived from adenovirus (ChAdOx1) taken from chimpanzees. This is a harmless, weakened adenovirus that usually causes the common cold in chimps. It is genetically engineered so that it does not replicate itself in humans. Now, a gene (the load) from the coronavirus, SARS CoV-2, that instructs cells to build spike proteins is loaded into the vector.
Remember, coronaviruses have club-shaped spikes on their outer coats — the ‘corona’. These spike proteins allow the virus to attach to the ACE2 receptors in human cells. When the genetically engineered ChAdOx1 with the spike-responsible gene from coronavirus is administered in a person, the gene is “expressed”, causing the build-up of spike proteins. The body’s immune system recognises this and begins to create the antibodies to defeat the foreign object. Note: the vaccine vector is non-replicant so it doesn’t harm the person, but the spike proteins nevertheless trigger antibodies. The preliminary findings showed participants also produced T cells, a type of white blood cell that “remembers” and attacks the coronavirus infection. Oxford researchers led by Professor Sarah Gilbert were able to quickly develop the vaccine candidate as they had been working on the ChAdOx1 platform against Ebola and MERS viruses.
And other vaccine candidates?
India’s hope: Pune-based Serum Institute of India, under an agreement with AstraZeneca, is to bulk produce the Oxford vaccine. The company’s CEO, Adar Poonawalla, had earlier said it will produce 5 million doses per month for the first 6 months before ramping up the production.
The findings are from the phase-I/II trial. The larger, phase-III trials of the vaccine have already begun in Brazil and South Africa.
A vaccine being developed by China’s CanSino Biologics and China’s military research also appeared to safely induce both antibodies and T cells, a mid-stage study released Monday said. Both CanSino’s and Oxford’s vaccines are based on a similar science of using a non-replicating viral vector to trigger the immune response.
Hyderabad-based Bharat Biotech has announced that the Phase-I clinical trials of India’s first indigenous Covid-19 vaccine Covaxin began across the country on July 15.
“This is a randomized, double-blind, placebo-controlled clinical trial on 375 volunteers in India,” the company said in a brief statement.
The leading vaccine maker had announced on June 29 that it successfully developed Covaxin in collaboration with the Indian Council of Medical Research (ICMR) and National Institute of Virology.
The SARS-CoV-2 strain was isolated in NIV, Pune and transferred to Bharat Biotech. The indigenous, inactivated vaccine was developed and manufactured in Bharat Biotech’s BSL-3A (Bio-Safety Level 3) High Containment facility located in Genome Valley, Hyderabad.
The vaccine developed by China’s CanSino Biologics in partnership with the country’s military research wing also relies on a viral vector, but a weakened human cold virus, adenovirus 5 (Ad5). CanSino, too, published its findings from phase I/II trial on Monday that showed it safely prompted an immune response.
But… the vaccine was inadequate to induce immunity response in people aged 55 or older — a group vulnerable to Covid-19. Researchers contend an additional dose given between the third and sixth month could negate this.
The use of Ad5 itself has left some scientists unconvinced. Since most people would have already been infected by Ad5 (cold virus), they fear the immune system induced would focus on the Ad5 parts of the vaccine rather than the SARS-Cov-2 material fused to it.
Two other advance candidates are developed by Massachusetts-based Moderna and Germany’s BioNTech in partnership with Pfizer. These are messenger-RNA based candidates. They rely on synthetic mRNA that delivers the genetic code for spike proteins, thus triggering an immune response. Early findings by Moderna and BioNTech-Pfizer, too, showed they prompted an immune response.
Another reason to be hopeful about the Oxford vaccine: Viral vector-based vaccines need only be cold stored, whereas mRNA vaccines need to be in a frozen state — a challenge for developing countries.