by Peter Westmore
With the cost of the covid19 pandemic measured in tens of millions of infections, a million deaths worldwide, and an unprecedented economic impact, there is understandable anticipation about the prospects of a safe, effective and ethically produced covid vax (vaccine) which will protect people from covid19 for at least some time.
There are three major problems facing possible covid19 vaccines: finding and testing suitable candidates; overcoming ethical issues with particular vaccines; and manufacturing sufficient doses to protect the seven billion people on Earth. (See News Weekly‘s coverage of covid19 here).
Many previously common viral diseases have been stopped by vaccination, including polio, tuberculosis (TB), measles, smallpox and mumps. Vaccines have also provided incomplete protection against other diseases, like influenza. No vaccines have been developed against other viruses, like the covid viruses that cause the common cold.
While development of a successful vaccine is still not certain, we know that many of the potential vaccines under development do at least prompt the human body to produce antibodies to fight the virus. Whether that response is sufficient to stop the virus completely for more than a short period, only time will tell.
Many people wonder why it will take at least a year for a vaccine to become available.
Covid19 is a new virus which apparently first appeared in Wuhan, China, late in 2019, but first reported in January 2020. Extensive biological studies took place before the complete genetic make-up of the virus was discovered and made public late in January.
Researchers then had to look at the new virus to determine how to create a vaccine which would prevent the virus from infecting human beings or, if it could not be prevented, at least to mitigate the effects of infection.
Since January, medical researchers from many countries around the world – often with huge financial support from governments – have set out to find and deliver a safe and effective vaccine that could be distributed throughout the world.
Currently, 165 teams are working on this project.
Experience over the past century has shown that some vaccines directly injected into the body are potentially dangerous, and so a careful process involving six sequential steps must be completed successfully before a vaccine is approved for general use.
These six steps are: 1) identification of a possible vaccine; 2) preclinical trials on animals for safety and efficacy; 3) phase 1 safety trials on a small number of people; 4) phase 2 trials on hundreds of people; 5) phase 3 trials “in the field” where tens of thousands of people are exposed to covid19; and, if all these are successful, 6) regulatory approval.
Vaccine development usually takes five to 10 years, but is being accelerated to a single year because of the impact of covid19.
Because there has never been a vaccine developed against any of the six other coronaviruses, different researchers are employing different approaches. Researchers are using the following approaches:
- Genetic vaccines that use one or more of the covid19’s own genes to provoke an immune response. U.S. company Moderna and German company BioNTech, for example, are both now in phase 3 trials.
- Vaccines that use another virus to deliver coronavirus genes into cells. The cells make viral proteins, provoking an immune response, but the virus cannot replicate. Among companies taking this path are AstraZeneca, the English-Swedish company from which Australia has pre-ordered millions of doses, CanSino Biologics, a Chinese manufacturer, and the Russian Gamaleya Research Institute of Epidemiology and Microbiology’s Sputnik-V vaccine. All these are now in phase 3 trials.
- Protein-based vaccines that use a coronavirus protein or a protein fragment to provoke an immune response. Among the targets of these vaccines are the spikes that covid19 uses to bind the virus to cells. The University of Queensland, in association with CSL, is in stage 2 trials, and Adelaide-based company Vaxine also has a vaccine, called Covax-19, which targets the spike protein. Other companies developing similar vaccines are Novavax, an American company which has received $US1.6 billion (over $A2 billion) from the U.S. Government, two Chinese companies, two Taiwanese companies, and a Russian company producing a vaccine called EpiVacCorona.
- Whole-virus vaccines use weakened or inactivated viruses to provoke an immune response. At least four Chinese companies are developing such a vaccine, with an inactivated vaccine called CoronaVac now in phase 3 trials. Additionally, an Indian biotech company is testing a vaccine called Covaxin based on an inactivated form of the coronavirus. American pharmaceutical company Merck is testing a vaccine that uses weakened measles virus to carry genetic material into patients’ cells.
- Repurposed vaccines include the Murdoch Institute’s modified BCG vaccine, originally developed over 100 years ago to treat tuberculosis, and now in phase 3 trials. Similar vaccines are also being developed by a number of other companies in different countries, but none has reached phase 3 trials except for the Murdoch Institute.
The wide range of different approaches being taken to vaccine development substantially enhances the prospect that safe and effective vaccines will be produced to counter covid19.
There are now 36 possible vaccines currently undergoing human trials, of which nine are in phase 3 trials, indicating that they have already shown a capacity to produce antibodies to covid19. Final trials will assess their safety.
Only when large-scale phase 3 trials have been completed successfully with minimal side effects, and have shown that they confer immunity on a majority of those tested, can the developers apply for approval to distribute a vaccine. In light of the fact that nine vaccines have already passed limited human testing and are now in stage 3 tests – and a further 14 are in phase 2 human tests – it is probable that at least one of these will be approved for general release either later this year, or in 2021.
As vaccines must be approved prior to large-scale manufacturing and distribution, they will likely become available only in six to 12 months.
Second, there are ethical issues. One involves the use of aborted fetal tissue in the development of the vaccine, and the second concerns “challenge” trials, where volunteers are deliberately infected with covid19 in order to test the efficacy of a vaccine.
Three prominent church leaders have questioned the Prime Minister’s decision to commit to the AstraZeneca vaccine, which has used cell lines from aborted babies in its development.
Anglican Archbishop of Sydney, Glenn Davies, Catholic Archbishop Anthony Fisher, and Greek Orthodox Archbishop Makarios co-signed a letter (August 20) to Scott Morrison requesting that the Government investigate ethical alternatives to the AstraZeneca vaccine.
They expressed concern that the AstraZeneca vaccine made use of “a cell line cultured from an electively aborted human fetus …”.
“While we accept that the proposed [AstraZeneca] vaccine may be sufficiently remote from the abortion that occasioned the derivation of the cell-line, we flag to you that any covid19 vaccine cultured on a fetal cell-line will raise serious issues of conscience for a proportion of our population …
“It is in the best interests of the community that vaccination is widely taken up and this deadly disease defeated, and this will better be achieved if the vaccines available do no create an ethical quandary.”
A separate issue involves the ethics of “challenge” trials, in which volunteers are given the candidate vaccine, then infected with covid19 to test its effectiveness.
Some ethicists approve “challenge” trials and point out that those who participate are volunteers, no different from health workers who put their lives on the line during the pandemic, or firefighters who do the same during bushfires.
Other ethicists, like Ben Bramble, who is Visiting Faculty Fellow at Princeton University and a lecturer in philosophy at the Australian National University, consider that such trials unfairly exploit volunteers who cannot evaluate the risk of taking part in a trial when much remains unknown about the virus.
He argues that vaccines should be tested in the general community, without “challenge” trials.
It is not known whether “challenge” trials will be held in Australia.
Further, many scientists have warned against making vaccines as compulsory as possible.
They argue that if one compulsory vaccine is later found to have safety issues, people will be reluctant later to accept a vaccine that is safe.
The final issue for covid19 vaccines is whether they will be readily available around the world.
The World Health Organisation has called on countries and pharmaceutical companies to make them universally available.
Many countries that are developing vaccines have already agreed to make them available internationally, and licensing agreements will undoubtedly enable successful vaccines to be manufactured in many countries to meet the huge demand.
Australia has already announced that it will expedite delivery to the small island states in our region, and European countries are likely to do that same for Africa and the Middle East.
In most countries, including Australia, the delivery of vaccines will be made a priority to people working in health and aged care, and then to those sectors of the community most vulnerable to covid19 – the aged and those with chronic health conditions.
Until this is done, the covid19 pandemic will not come to an end.