The United States’ drug regulator, the Food and Drug Administration (FDA), said last week COVID vaccines updated for variants won’t need to go through full randomised controlled clinical trials.
The booster shots will only be required to undergo initial testing to check they are safe and produce an immune response. They won’t need to go through lengthy “phase 3” efficacy trials which would normally enrol tens of thousands of participants.
The European Medicines Agency hasn’t published formal guidelines, but has taken the same position. Chair of the agency’s vaccine evaluation team, Marco Cavaleri, told Reuters: “We will ask for much smaller trials, with a few hundred participants, rather than 30,000 to 40,000”. The focus would be primarily on safety and immune response data.
This is encouraging news, because it means we could get access to booster shots much more quickly than if they went through full trials. And because drug companies will have to prove they’re using the same technology and manufacturing process as the original vaccines, we can still be assured they’ll also be safe.
Australia’s Therapeutic Goods Administration (TGA) has not yet confirmed whether it’ll do the same, but history tells us we can probably expect it to follow suit.
Why Do We Need Boosters?
Variant strains of the virus have been detected around the world, including those originating in the UK, South Africa and Brazil. People infected with these variants have been found in Australian hotel quarantine, and the B.1.1.7 strain, first found in the UK, has escaped the quarantine system several times.
For those tested, the current crop of vaccines still perform relatively well against the B.1.1.7 strain.
And data suggest most COVID vaccines will still be somewhat useful in preventing hospitalisation and death from these variants.
However, efficacy against mild to moderate illness, and against transmission of the virus, has likely dropped off sharply against some of these variants.
For example, preliminary data suggest vaccine efficacy for AstraZeneca’s vaccine dropped to just 10% against mild-moderate illness from the B.1.351 variant which originated in South Africa. Efficacy of Novavax’s shot slid from 89% to 60% against this variant. These data were from small trials and more studies are needed, but it’s still very concerning.
We don’t have solid real world data yet about the performance of the Pfizer vaccine against the B.1.351 variant.
Why Don’t We Need Full Trials Again?
Drug companies have flagged the need to develop updated booster shots to cover these new variants, which would involve tweaking their sequences.
Some scientists were worried this would mean drug companies would have to go through full randomised controlled clinical trials, including large phase 3 efficacy trials, to get these booster shots to market. These phase 3 clinical trials include many thousands of volunteers and the primary aim is to determine if the vaccine can prevent people from getting the disease.
By the time these trials were completed, it may be too late to control outbreaks caused by variants, and new variants may emerge that we’d need coverage for. In a pandemic, we don’t have the luxury of time.
But the FDA has dispelled this fear. The drug regulator seems most interested in ensuring any booster shots are safe and the manufacturing process hasn’t been modified from the original vaccines it approved.
The boosters will still require smaller trials to show they’re safe and generate an immune response. The trials typically involve a few hundred people and would examine the percentage of vaccinated volunteers who make antibodies to the variants, as well as the strength of the immune response.
This would be similar to what’s done for annual flu shots, although not exactly the same. We get very different flu strains circulating every few years, but current COVID-19 vaccines and variant “boosters” could be sufficient to use for several years — we don’t know yet.
The FDA also indicated boosters won’t necessarily need to undergo animal testing before progressing to human testing, which will also save time. But this may be encouraged if results from human trials are ambiguous.
How Do We Know They’ll Be Safe and Effective?
Any potential side effects from a vaccine are mostly based on how the vaccine is made, the technology and how it’s delivered.
If drug companies keep all these factors the same, and only make minor sequence changes to cover variants, then we can expect the boosters to still be very safe vaccines.
The US and EU drug regulators would like to see data where the booster is given to people who’ve already had an original COVID vaccine, given this will be the likely scenario for most people receiving a booster shot by the time they’re approved.
The boosters will probably also be tested in people who haven’t had any COVID disease or vaccine. This is to ensure the boosters can induce strong immune responses like the original vaccine.
When required, the TGA will independently review all of this data. It will also likely seek advice from internal and external experts.
It’s also unclear when booster shots will be available or if they will be necessary in the short term. Melbourne-based biotech company CSL, which is producing the AstraZeneca vaccine onshore, said this week booster shots to cover coronavirus variants probably won’t be available until the end of the year.
US pharmaceutical company Moderna has already sent a new COVID vaccine booster shot for phase 1 testing, to target the B.1.351 variant. Pfizer is also planning to develop a booster to cover this variant, either as a third dose or a reformulated vaccine.
New variants will continue to arise, but the best chance we have of stopping or slowing this process is by continuing public health measures to ensure as few people as possible become infected.
This includes vaccinating as many people as possible globally with the currently approved vaccines, which underscores Australia’s responsibility to assist countries in our region in getting vaccinated.
ABOUT THE AUTHORS
Jamie Triccas is a Group Leader at the University of Sydney whose laboratory studies how lung pathogens interact with the immune system, and how this information can be used to develop new strategies to treat infection. Professor Triccas is head of the Microbial Immunity and Pathogenesis Group located in the Discipline of Infectious Diseases and Immunology at the University of Sydney. He received both his BSc (Hons) and PhD from the University of Sydney. He was previously a Cantarini Research Fellow at the Pasteur Institute in Paris (1997-1999) and a Senior Research Fellow at the Centenary Institute in Sydney (1999-2004). The research program of Professor Triccas is focused on determining how virulent micro-organisms promote disease and developing novel strategies to prevent infection. Over the last 10 years he has focused his efforts on the development of new tuberculosis vaccines and drugs, and a number of these candidates are nearing clinical trials in humans. The group is also defining in detail the T cell immune response induced by infection with virulent lung pathogens, by the use of T cell receptor transgenic models developed in the laboratory. It is hoped that such studies will aid the rational design of new vaccines engineered to stimulate immune function. More recently, Professor Triccas has commenced projects aimed at discovering new compounds that could be used as treatments to control infection with the lung pathogens Mycobacterium tuberculosis and Methicillin-resistant Staphylococcus aureus (MRSA), a major cause skin and other serious infections.
Anthony (Tony) Cunningham AO, FAHMS, is an infectious diseases physician, clinical virologist and scientist, well known internationally for his research on the immunobiology of HIV and herpesviruses, his work on vaccine development and trialling, especially for shingles and herpes, and as an antivirals expert. He has served on numerous international expert panels on HIV/HSV, antivirals and vaccines. Professor Cunningham is Professor in the Faculty of Medicine and Health at the University of Sydney, the Director of the Centre for Virus Research at The Westmead Institute for Medical Research (WIMR) and Director of the Australian Centre for HIV and Hepatitis Virology Research (ACH2). ACH2 is a Commonwealth funded institute that aims to combat the impact of HIV and hepatitis in Australia and the Asia Pacific region, by bringing together basic researchers with translational scientists and physicians. He previously trained at Stanford University, USA and built up NSW State Reference Laboratory in Virology in the mid-1980s, before assuming directorship of WIMR in 1996. In 2010, he was awarded Officer of the Order of Australia (AO) for ‘service to medicine, particularly in the field of viral research and through the development and leadership of medical and biomedical research’ and in 2015 was elected as an inaugural fellow of the Australian Academy of Health and Medical Sciences. Since stepping down from the WIMR director role at the end of 2019, Professor Cunningham has continued his research on his NHMRC senior Investigator Grant and become immersed in COVID-19 research, amongst other advisory positions including the NSW COVID Vaccines Committee.
This article is courtesy of The Conversation.