Coronavirus Mutation Unlikely to Adversely Impact Vaccine Efficacy, But We Must Remain Vigilant

Global Experts Discuss Challenges and Prospects of Covid-19 Vaccine in Saudi Forum 

As the pandemic rages on, pressures are mounting to get a vaccine available for use as soon as possible. The 11th KAIMRC Annual Forum for Medical Research was held virtually this week to discuss global challenges and prospects of a Covid-19 vaccine. Thirty-two international experts from global academic institutions including the Universities of Oxford, Harvard, and Stanford participated in the 2-day forum to review all aspects of vaccine development and production to ensure global participation from decision-makers, media outlets, health workers and the general public.

HOW CLOSE ARE WE TO A VACCINE?

The race for a COVID-19 vaccine is edging towards the finishing line, but with the continuing rising of cases and countries going into second lockdowns, many are wondering more than ever if we are any closer to a vaccine. A coronavirus vaccine could be the vital game-changer in this pandemic to save lives and ensure no further lockdowns are needed.

Governments around the world are making a big bet that the first vaccines for COVID-19 could be made with genetically engineered viruses such as the AstraZeneca/Oxford and the Harvard/J&J vaccines. The engineered viruses, called adenoviral vectors, are designed to shuttle a gene from SARS-CoV-2, the novel coronavirus that causes COVID-19, into our bodies where our cells will read it and make coronavirus spike proteins. 

Some scientists say that adenoviral vector vaccines, and Oxford’s vaccine, in particular, may be society’s best chance for a return to normalcy. Dr Sarah Gilbert Professor of Vaccinology at the University of Oxford and lead on the Oxford vaccine trial, says that we still cannot predict at this stage when these vaccines will be rolled out.

“It is impossible to know as it is going to take some months even after we have efficacy results and regulatory approval to then immunise large parts of the population. Moreover, when we do come to vaccine roll-out, it will not be the entire population that gets the vaccine on the same day, so there has to be a process of prioritisation within countries to decide whom to give the vaccine to first. The two top targets groups are healthcare workers and the older part of the population,” she said during a discussion led by forum Co-Chairman Dr Ahmed Salman, Senior Immunologist-Vaccinologist at The Jenner Institute, University of Oxford.

“We expect to be starting this process in terms of getting the efficacy results and then moving forward to applying for regulatory approval by the end of the year,” she added.
 

Sarah Gilbert Professor of Vaccinology at the University of Oxford and lead on the Oxford vaccine trial.


Dr Dan Barouch, a vaccine researcher at Harvard and collaborator on Johnson & Johnson’s vaccine, echoed Dr Gilbert’s sentiments.

“I think we have to be very careful about giving calendar dates as dates previously proposed and have now been revised. It is difficult to predict when the phase III trial will end, and when they do end, if they show efficacy, there will still be a period for regulatory review and approval as well as the actual rollout, assuming that manufacturing is not a factor,” he said.

“There are many uncertainties, but if everything goes well, we are hoping for efficacy data by the end of this calendar year, possibly the beginning of 2021,” he added.

COULD VIRUS MUTATION HAMPER VACCINE DEVELOPMENT?

Most vaccines under development worldwide have been modelled on the original ‘D-strain’ of the virus, which were more common amongst sequences published early in the pandemic. Since then, the virus has evolved to the globally dominant ‘G-strain’, which now accounts for about 85 percent of published SARS-CoV-2 genomes. There had been fears the G-strain, within the main protein on the surface of the virus, would negatively impact on vaccines under development. 

In response to Majalla’s question regarding virus mutation, experts assured that they had found no evidence that the change would adversely impact the efficacy of vaccine candidates.

“So far, we have not seen any drop in the ability of antibodies induced by vaccination to neutralise the spike protein that is now in circulation. Obviously we have to keep an eye on mutations that arise, and it would be possible with this type of technology to insert a different spike protein once it is necessary, but as of yet we have not seen any indication that this is going to be necessary,” said Professor Sarah Gilbert.

Dr Dan Barouch said that the mutations that have arisen to date do not appear to impact neutralisation and therefore J&J are optimistic that the current vaccines under development around the world will be effective. “However,” he added, “I think we need to remain vigilant.”

“There is a theoretical possibility that since virtually all the vaccines are currently in trials today are based on the original sequence from Wuhan, that there could be a risk of cross-resistance. I am optimistic that it is a virus that does not mutate very quickly; however, I do think that the scientific community should remain vigilant and continue to sequence viruses for possible resistance.  However, as of now, we believe that the current viruses should be sensitive to neutralising antibody titers raised by these vaccines,” he said.
 
Dr. Dan Barouch, a vaccine researcher at Harvard and collaborator on Johnson & Johnson’s vaccine.


LONGEVITY OF THE IMMUNE RESPONSE

Since the onset of the coronavirus outbreak, a vaccine has been widely regarded as the best path toward reopening society and returning to normalcy.  Yet, despite these Herculean efforts, scientists say a one-time cure-all is unlikely. Data on close cousins of the COVID-19 virus, suggests the COVID-19 vaccine will offer short-term protection -- although more research is needed to understand how well and for how long a potential vaccine could work.

“We do not have preclinical data on the durability of the coronavirus vaccine, but clinical data from our MERS coronavirus vaccine showed that vaccine-induced protection in the subjects that we immunised had immune responses a year after vaccination,” said Sarah Gilbert Professor of Vaccinology at the University of Oxford and lead on the Oxford vaccine trial.

“Therefore, we certainly expect that our Covid-19 vaccine will provide an immune response for up to a year after vaccination. As part of our clinical trials, we will continue to follow up with our volunteers to look at the persistence of those immune responses, but it is not data that we have yet,” she added.

Dr Dan Barouch, a vaccine researcher at Harvard and collaborator on Johnson & Johnson’s vaccine, says that while durability data in monkeys and humans are not yet available as those studies take longer to complete, J&J does have data on the durability of the Zika and HIV vaccines which is “very good in humans as well as monkeys.”

Still, “there can be differences, so we have to wait to empirically measure the durability of the covid-19 vaccine in animals and humans.”

When researchers tracked COVID-19 patients over time, they found that the amount of antibody peaked in the days following the onset of symptoms, then began to decline. In some study participants, the antibodies were practically undetectable within about three months. Several major media outlets reported this as a loss of immunity, saying that it would complicate vaccine efforts.

In a discussion on Saudi Academic Efforts for COVID-19 Sciences and Vaccines, Dr Naif Alharbi, Director of Vaccine Development at King Abdullah International Medical Research Center, said that while reinfection is happing, it is still considered rare and does not mean that a vaccine will be less effective.

“If your first infection is severe, you are less likely to get another infection, but if it is mild or asymptomatic, you are more likely to get a second infection because your body did not induce antibodies that are strong enough and therefore diminish more quickly over time,” he said.
 
Dr. Naif Alharbi, Director of Vaccine Development at King Abdullah International Medical Research Center.

“I do not believe that this is a counter issue for vaccine development. We found from our MERS vaccine trials on camels that while camels can become re-infected multiple times, once they are vaccinated, enough antibodies are produced to protect them against reinfection,” he added.

“Any vaccine that induces a good immune response for a year would be able to break the chain of the virus and bring it under control. A vaccine is not a miracle solution, but a method of controlling the virus.”

Dr al-Harbi also noted that there are age-related changes in immune function. 

“It is important to evaluate the vaccine in the older population as it is expected that the immune response ageing decreases antibody responses. However, we have seen data from some vaccine developers that so for the results seem promising in the above 65 age group.”

LESSONS LEARNED

Beyond immediate priority of everyone’s health and livelihoods, the crisis is an opportunity to rethink the way we plan, develop and manage future vaccines, to make sure better prepared to protect everyone when the next emergency arises, said Professor Adrian Hill, founder and director of the University of Oxford’s Jenner Institute.

“Peacetime” vaccine development is far too slow. The reason that normal vaccine development takes a decade although when it can be done in a year although you are doing the same trials, same review bodies and have to overcome the same hurdles, it is all to do with the time it takes to do the administrative stuff, and not because it takes a decade to test the vaccine’s safety,” he said.

“The field has shown that you can get lots of vaccines right through to phase III and efficacy assessments in a year.  While I do not think that we will generally be making vaccine in a year in the future but three years would be a bit more realistic,” he added.
 
Professor Adrian Hill, founder and director of the University of Oxford’s Jenner Institute.


Professor Hill also emphasised that the pandemic has brought light that vaccines and vaccinologists are underrated and not believed by the government. 

“We shouted after Ebola, we made a fuss with swine flu, and we pointed out that the risks were there of something much nastier than swine flu come about. Virologists produced data of what the risks were, and epidemiologists predicted what might happen, and well, it happened - there is a major global pandemic, and we should have been better prepared.” He said.

“The IMF said last week that the likely economic cost of Covid in terms of lost economic development will be in the order of tens of millions of dollars. With that in mind, investing in being better prepared would have been a good investment.”