With Covid-19 vaccines in the final phase of the study now, you may have wondered how the FDA will decide if a vaccine is safe and effective.
According to the status of the current trials it is unlikely that the results of these trials will be available before November.
But it is likely that by the end of 2020 not just one, but several of the competing covid-19-vaccines will prove safe and effective.
at the University of Virginia, where I have the job of caregiving patients with Covid-19 and conducting research on pandemics.
I am also a member of the WHO Expert Group on Covid-19 Vaccine Prioritization
What is the status of the Covid-19 vaccine in human clinical trials?
for the moderna and biotech/pfizer vaccines and the Oxford/AstraZeneca virus-vector – vaccine.
Each of these vaccines uses the SARS-CoV-2 spike glycoprotein that the virus uses to infect cells to trigger the immune system to produce protective antibodies and cellular immunity to the virus.
Protective antibodies act by blocking the spike glycoprotein from attaching the virus to human cells and thus neutralizing the SARS CoV-2 virus that causes COVID-19.
In the case of spike glucoproteins the messenger RNA is wrapped in a fat droplet – called a liposome – to protect the mRNA from degradation and enable it to enter cells.
Once these instructions are inside the cells, the mRNA is read by the human cell machinery and converted into many spike proteins so that the immune system can respond and produce antibodies against this coronavirus.
Oxford and AstraZeneca use a different strategy to activate an immune response.
Here an adenovirus found in chimpanzees has the instructions for glucose production in cells.
Using the VPS also similar to Oxford / AstraZeneca – Vaccines, vaccines from Novavax and GSK-Sanofi also use actual spike protein itself.
Animal tests show that the vaccines give protection against a coronavirus-infection
In animal models of COVID-19, studies provide convincing evidence that an HPG-immunization with the spike glycoprotein will protect against COVID-19.
Experiments have shown that when the immune system is analyzed by the spike protein – which alone can not cause disease – the immune system generates an antibody response that protects from infection with SARS-CoV-2.
One adenovirus-virus vector used by Oxford/AstraZeneca for example was used to immunize with Spike glycoprotein.
When the Hamsters were infected with SARS CoV-2 they were protected from pneumonia, weight loss, and death.
, DNA-Victoria – which deliver the gene for spike glycoprotein – decreased the volume of virus in the lungs.
Animals that produced antibody that prevents the attachment of virus to human cells were the most likely to be protected.
Histories of the vaccines: Smallpox to SARS-CoV-2
What have shown the early phase 1 and two studies of human comparison?
Overall, than this observed in patients who suffered from Covid-19.
This has also been the case for and for vaccins
What side effects have been noticed?
Vaccination up to 28 days after immunisation is being carried out
These side effects included mild pain, warmth and discomfort at the site of injections and fever, fatigue, joint and muscle pains.
But phase 1 and 2 studies are by design tiny and have only hundreds of participants.
Because these trials will not be big enough to detect unusual or rare side effects.
The emphasis on safety as the primary objective was demonstrated in the study phase 3 Oxford / AstraZeneca Vaccine.
It isn’t clear whether the vaccine sparked this reaction – it might be a new case of multiple sclerosis not related to the vaccine – but the phase 3 trial was stopped in the US until more is known.
How is the FDA able to ensure that a vaccine will be safe but not produced rapid?
These are the same standard of rigorous safety requirements for all vaccines on the steps required for the development and ultimately licensing of vaccins to stop Covid-19.
There are, however, ways to speed the approval process that rely on platform technology , which means that if a vaccine is used in an approach such as an adenovirus that has previously been shown to be safe, it might be possible for a company to use previously collected data on toxicity and pharmacokinetics to improve clinical trial approval.
Although speed and safety may appear conflicting goals, it is also encouraging to note that of non-evolve governmental pressure to expedite the approval of vaccines, but to maintain the strictest safety standards.
How to Develop a vaccine quickly?
How protective must a vaccine be to get FDA approval?
The FDA lowered the bar for the primary endpoint of a Phase III trial of 50% protection for approval of Covid-19 vaccine
Protection is defined as protection from the symptomatic Covid-19 infection, defined as laboratory-confirmed SARS-CoV-2 infection plus symptoms like fever or chills, coughing, shortness of breath, fatigue, muscle aches, indigestion or smell, congestion or runny nose, diarrhea, nausea or vomiting.
This means that an effective vaccine is considered one that will reduce the number of infections in vaccine recipient by halving.
That is, in part, because lower efficacy could paradoxically raise Covid-19-infections if it leads vaccinated people to decrease mask wearing or social distancing because they think they are totally protected.
Since a vaccine could be more effective at preventing severe Covid-19, the FDA makes recommendation that one secondary endpoint should be ;
How many people must be vaccinated for knowing if a vaccine works in Phase 3?
Phase 3 trials are currently enrolling 30,000 — 40,000 subjects.
Most of these participants will get the vaccine, and some a placebo.
The timing of release of the results of Phase 3 studies depended in part on the rate of infection of the placebo recipient.
These vaccine studies work by testing if the natural acquired new coronavirus infections are lower in the group that received the vaccine compared to the group who received placebo.
So while it is good news that recent covid-19 infections from States have decreased in the U.S, this fall in new infections may slow down vaccine studies.
Will the emergency use authorization swiftly effect vaccines?
In a situation such as our Covid-19 pandemic currently, with approximately 700 new deaths and 40,000 new cases each day, FDA is authorized to allow the use of nonapproved drugs for diagnosis, treatment and prevention of disease.
Those include a vaccine.
While being vaccinated for at least a year, they can require more than one year of observation.
If the short term safety is good and the vaccine works to prevent Covid-19, then the vaccine should be approved under an emergency use authorization for use while the virus is still being investigated.
Under Emergency Use Authorization, the FDA will provide cost-saving and benefits monitoring for vaccination related enhanced respiratory disease or other potentially rare complications that could be observed only in one in a million companies whose vaccines have produced.
What is a valid order in terms of approvals?
I am expecting that the FDA will approve several vaccines by the end of 2020 under its Emergency Use Authorization Agreement so that vaccination could start immediately, starting with high risk groups such as First Responders, health care professionals and the elderly and those with preexisting medical conditions.
This will be quickly followed by the population at large, while FDA and vaccine manufacturers will always monitor for side effects and work towards improving these first vaccines.
This process is .
It may not be a year from now to return to normals, but all signs point to a healthier 2021.
This article was first published at the University of Virginia