Moderna and Pfizer/BioNTech both announced in November that their vaccine candidates against the novel coronavirus have shown promising preliminary results in Phase 3 clinical trials. The two vaccines are among several that have been preordered by the Canadian government. So how close are we to getting the vaccine? What needs to happen first? And what kind of vaccine is this anyway? CBC readers have also written to us with some of their own questions, such as what are the side effects of these vaccines? How long does the protection last? And when can Canadians expect to get access? Here are the answers.
What did Moderna and Pfizer announce about their vaccine results?
Moderna announced on Nov. 16 that preliminary data from its ongoing Phase 3 clinical trial shows the vaccine is 94.5 per cent effective at preventing COVID-19 caused by the coronavirus.
Similarly, Pfizer had said on Nov. 9 that interim analysis of data from its Phase 3 clinical trial, which is also still ongoing, suggests its vaccine may be 90 per cent effective at preventing COVID-19.
The analyses were both conducted by an independent data monitoring board. Pfizer’s looked at 94 infections, and Moderna’s looked at 95 infections recorded so far during the trial to see which occurred among those who received the real shot versus those who received a dummy shot or placebo. With both vaccines, each participant gets two injections.
Moderna said of the 95 infections, all but five were in participants who got the placebo. In addition, all 11 severe cases of COVID-19 were among those who had received the placebo. Pfizer did not say how many infections occurred in each group, but a 90 per cent effectiveness would imply that no more than eight of the infections were in the group that received the vaccine, Reuters reported, assuming equal numbers of volunteers in the group that received the vaccine and the group that received the placebo.
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What don’t we know based on these results? Why might the final results be different?
The results are preliminary, and the initial protection rate might change by the time the study ends, both companies cautioned.
Moderna’s analysis looked for cases starting two weeks after the second dose of the vaccine. The Pfizer analysis so far looked for cases of COVID-19 seven days after the second dose. Pfizer has now said it will also look for cases 14 days after the second dose.
If the shots wear off quickly, the infection rate could go up among those who received them.
Pfizer did not say how many of the infections occurred in older adults. Moderna said 15 of the infections so far occurred in older people, who are at highest risk from the disease, but did not say how many were in the vaccine group or the placebo group. (Vaccines are often less effective in older populations, which is why there are higher-dose flu and shingles vaccines for seniors.)
Do the vaccines just stop symptoms or prevent infection?
We don’t know yet. So far, only people with symptoms have been tested in these trials, as that is the “primary endpoint” of the study — the first thing that they look for. That means it’s not clear if there are asymptomatic infections and whether vaccinated people can unknowingly spread the disease.
Moderna says key “secondary endpoints” of its clinical trial are to see if the vaccine:
- Prevents severe disease. (The company did say that all 11 of its volunteers who got severe COVID-19 were in the placebo group, suggesting that it does).
- Prevents infection (including asymptomatic infection).
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The final data has not been analyzed, peer reviewed or published for either study. Moderna and Pfizer say they will submit the data to a scientific peer-review publication once they’re complete.
How well do the vaccines need to work to be approved?
The U.S. Food and Drug Administration has said a vaccine must be at least 50 per cent effective to be approved, ideally for preventing the disease but possibly for only preventing severe disease.
The World Health Organization recommends that, at minimum, it wants a clear demonstration that the vaccine is effective at least 50 per cent of the time in preventing the disease, preventing severe disease or preventing shedding or transmission. However, it says it prefers vaccines to have at least 70 per cent efficacy across the whole population, with consistent results in the elderly.
WHO also said the vaccine must confer protection for at least six months and ideally at least one year.
What kind of trials were these? How far along were they?
These were Phase 3 clinical trials, the final human trial step before regulatory approval. While Phase 1 and Phase 2 studies are focused mainly on safety, dosing and lab indicators of an immune response, Phase 3 trials answer a key question: are those who get the vaccine protected from the disease compared to those who get a placebo? It could also reveal rarer side-effects that aren’t observed in smaller Phase 1 and 2 trials.
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Both trials started on July 27. So far, Pfizer’s study has enrolled more than 43,000 people in the United States, Argentina, Brazil, Germany, South Africa and Turkey. Moderna’s study has enrolled 30,000 in the U.S. In both studies, each person gets two shots, 28 days apart. Some get the real vaccine candidate, while the others get a placebo.
The Phase 3 trials will end when:
- At least half the participants have been tracked for side-effects for at least two months.
- Pfizer records 164 infections and Moderna records 151. That means Pfizer has 70 left to go, and Moderna has 56.
Pfizer said it will reach its tracking milestone later this month.
What kind of side effects did volunteers experience?
Pfizer had previously said that participants showed mild to moderate side effects when given either the vaccine or the placebo in the Phase 3 trial, but it was not specific.
Moderna said most side effects in its trial were mild or moderate, but less than 10 per cent of volunteers had more severe side effects. They included pain at the injection site after the first injection and sometimes fatigue, muscle aches, joint pain, headache and pain or redness at the injection site after the second injection. The doses used in the Phase 3 clinical trial are lower than those linked to severe “systemic” side effects in three participants in an earlier clinical trial.
What about long-term effects?
Both trials started so recently that it’s impossible to know if there are any. However, before approval can be sought for the vaccines, half of the volunteers must be followed for a minimum of two months, as most side effects show up within that time period. Pfizer says the volunteers will continue to be monitored “for long-term protection and safety” for two years after their second dose.
How were the trial participants infected or exposed with COVID-19?
They would have been infected in the community while going about their daily activities, such as work, school and social gatherings. Because of that, most vaccine trials choose countries with a high rate of infection to accumulate enough infections — and data — more quickly.
How big a deal is this? How optimistic should we be?
Infectious disease experts say the results are promising.
“It looks as if both these vaccines are going to work, and very likely both these vaccines are going to be rolling out early 2021,” Dr. Christopher Labos, a Montreal-based epidemiologist, told CBC News Network after Moderna’s announcement.
Dr. Bruce Aylward, WHO’s senior adviser, said following the Pfizer announcement that the vaccine could “fundamentally change the direction of this crisis” by March, when the UN agency hopes to start vaccinating high-risk groups.
Vaccines won’t be available immediately for the general public in Canada.
Dr. Caroline Quach, a paediatric infectious disease physician and medical microbiologist at Sainte-Justine Hospital in Montreal, cautioned we’re not “out of the woods” yet, and everyone still needs to practise safety measures, such as handwashing, staying home when sick, physical distancing and wearing non-medical masks.
That’s because independent experts haven’t yet seen the full data to determine if the clinical trial participants who received the vaccine and placebo were similar enough to draw conclusions.
Experts also caution that the roll out of the Pfizer/BioNTech vaccine to the general public will be slow, and logistical hurdles remain, such as the extremely cold temperature requirements for its genetic component. Moderna has said its vaccine is stable at fridge temperatures for a month and regular freezer temperatures are cold enough for long-term storage.
But widespread vaccine rollout is still months away – regardless of which one is available. <br><br>With cases/hospitalizations/deaths rising, it’s time to double down on our efforts and continue effective public health measures to keep the virus at bay…masking, distancing, etc.
What type of vaccine is this? What other front-runners are similar?
Both Moderna’s and Pfizer’s candidates are messenger RNA vaccines. Pfizer’s is officially called BNT162b2 and Moderna’s is known as mRNA-1273.
The vaccines consist of genetic instructions on how to make the modified spike protein from SARS-CoV-2, the coronavirus that causes COVID-19. The genes are encoded in mRNA and packaged in lipid nanoparticles. Once the vaccine is injected into the body, human cells use the instructions to make copies of the spike protein for the immune system to learn to recognize.
Pfizer’s technology includes Vancouver-based Acuitas Therapeutics’s lipid nanoparticles to deliver the mRNA after it’s injected into our cells.
Two other mRNA vaccines — CureVac’s and Arcturus Therapeutics/Duke-NUS’s candidates — are in Phase 2.
Canada also has a homegrown mRNA vaccine candidate that is currently in pre-clinical evaluation from Toronto-based Providence Therapeutics.
What are the advantages and disadvantages of this type of vaccine?
This type of vaccine does not contain any virus or viral proteins, which means it can’t cause a real infection and is considered safer.
It is also relatively quick to manufacture.
Alan Bernstein, a trained virologist and president and CEO of non-profit CIFAR, a Canadian-based global research organization that brings together top researchers to address important questions, called the Pfizer announcement “great results for humanity.”
“There’s never been a vaccine made from RNA, so this is opening up a whole new world of making vaccines if this result holds up,” said Bernstein, who previously led a major HIV vaccine effort.
However, the mRNA vaccine is a novel technology, and no vaccines of this type have been approved for widespread human use.
One disadvantage of mRNA is that it’s not very stable. That means it needs to be stored at very cold temperatures. BioNTech’s CEO says the vaccine needs to be kept at -70 C for longer-term storage, although the company says it can survive five days in a refrigerator.
That may make it logistically difficult to distribute, especially in less developed countries.
Moderna says its vaccine can survive a month in the fridge and can be stored for months at regular freezer temperatures of -20 C.
From a logistical standpoint – MUCH easier to transport.<br><br>”the vaccine can be kept in a conventional freezer at -20C for up to 6 months and that once thawed the vaccine can be kept for up to 30 days at standard refrigerator temperatures of 2 to 8C.”
WHO recommends that vaccines have a shelf life of at least two weeks in the fridge and at least six to 12 months at temperatures as low as -70 C. However, in the long-term, it says vaccines should be able to be stored at -20 C.
Do the proposed vaccines deal with live viruses or dead ones to stimulate antibody production?
No, not these two particular ones. However, there are some other teams around the world developing COVID-19 vaccines that use live, weakened live coronaviruses, dead or inactivated coronaviruses or live viruses such as the adenovirus cold virus that act as carriers for coronavirus genes.
How long would people be protected by these vaccines?
That’s not known. BioNTech CEO Ugur Sahin has said he expected the immune response from the Pfizer/BioNTech vaccine to last for “at least one year,” but he did not explain why he thought that.
How effective would it be for someone who is taking immunosuppressants?
That isn’t known. While both studies included people “at high risk of the severe complications of COVID-19 disease,”such as adults over 65 and younger adults with conditions such as diabetes, severe obesity and cardiac disease, they didn’t specifically mention people taking immunosuppressants. However, Moderna did say that preliminary analysis suggests a “broadly consistent safety and efficacy profile across all evaluated subgroups.”
What if we’re allergic to flu vaccines or eggs? Can we take this one?
Yes. Egg allergies are typically a concern with vaccines that are made in eggs. This one is not made in any live organism.
How much has Canada ordered?
Canada announced on Aug. 5 that it had preordered both the Moderna and the Pfizer/BioNTech vaccines. It later specified that it had reserved 20 million doses of each, with the option to purchase more. In the case of the Moderna vaccine, the agreement specifies that the federal government has the option to purchase another 36 million doses. Because two doses are required, Canada would initially have enough to vaccinate 10 million people with each vaccine if they are approved.
When will Canada get a vaccine?
Both Moderna’s and Pfizer’s vaccines are slated for delivery to Canadians sometime in 2021 if they are approved.
Besides those two, Canada has also pre-ordered vaccines from several other companies. Dr. Howard Njoo, Canada’s deputy chief public health officer, said on Tuesday that he expects all Canadians to be vaccinated against COVID-19 by the end of next year.
How much can Pfizer/BioNTech and Moderna manufacture?
Pfizer/BioNTech say they can produce up to 50 million vaccine doses in 2020 and up to 1.3 billion doses in 2021.
Besides Canada, they have already received preorders from other countries.
For the Pfizer vaccine, the U.S. has preordered the first 100 million doses, with option to add another 500 million. Pfizer and BioNTech say they can deliver 50 million of those doses by year end. The United Kingdom has ordered 30 million. The companies also have an agreement with the European Union for 200 million doses.
Moderna expects to have about 20 million doses, earmarked for the U.S. by the end of 2020. The U.S. has ordered a total of 100 million doses, with the option to acquire more. Moderna has also signed deals with Israel and Switzerland.
Both Moderna and Pfizer/BioNTech plan to ask the U.S. Food and Drug Administration for emergency use authorization of their vaccines once the trials are complete and the safety data analyzed.
Have a question?
Send your questions about this and other COVID-19 vaccine candidates to COVID@cbc.ca.
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