They've announced it as being 'more than 90% effective' in a Phase 3 trial, but what does this really mean? This former Harvard professor believes the fix was in from the start, and they're designed to be proven effective, even if the effects are minimal.
Pfizer, in a joint venture with BioNTech, announced that their mRNA-based COVID-19 vaccine candidate, BNT162b2, was “more than 90% effective” in a Phase 3 trial
While Pfizer did release a clinical protocol of its trial, it only issued a press release; data for the interim analysis has not been peer reviewed or published
Infectious disease expert William Haseltine criticized COVID-19 vaccine trials, including Pfizer’s, saying their protocols reveal that they’re “designed to prove their vaccines work, even if the measured effects are minimal”
Asymptomatic infections aren’t regularly being tested for in Pfizer’s trial, so it’s possible that those who have been vaccinated could still be asymptomatic carriers of COVID-19, spreading the disease to others
Also missing from Pfizer’s press release is how the vaccine fared in different age groups, a key data point since older people are those most at risk of serious disease outcomes
There is concern that COVID-19 vaccines could cause antibody-dependent enhancement, or ADE, in which the vaccine enhances the virus’ ability to enter and infect your cells, resulting in more severe disease than had you not been vaccinated
It’s far too soon to know whether the vaccine is safe, as, on average, it can take 10 to 12 years for a vaccine to be developed and go through the normal licensing process
With more than 180 COVID-19 vaccines currently in development1 — 53 of them undergoing clinical trials in humans2 — manufacturers are racing to be the first to reach the market. Pfizer, in a joint venture with Germany-based BioNTech, may have just taken the lead, with an announcement that their mRNA-based vaccine candidate, BNT162b2, was “more than 90% effective” in a Phase 3 trial.3
BNT162b2 was selected to move forward to a Phase 2/3 trial after an earlier version of the vaccine, BNT162b1— another mRNA-based vaccine candidate — resulted in considerable adverse events,4 including fever, which occurred in 50% of individuals who received the highest dose (100 micrograms), fatigue, headache and chills.
Side effects were even more common following the booster dose, after which more than 70% of participants experienced a fever at the mid-range (30 microgram) dose. In fact, those in the high-dose group didn’t even get the booster dose after the side effects were deemed to be potentially too severe.
While the vaccines are similar, with the BNT162b2 vaccine, mRNA encodes the full-length spike protein. A spike protein is a glycoprotein protruding from the envelope of a coronavirus that allows entry into the cell.5 In an earlier study, while BNT162b2 appeared to cause fewer side effects, antibody titers were lower in a group of older individuals, ranging in age from 65 to 95 years, than in younger individuals.6
Geometric mean titers (GMTs), which are used as a measure of immune response, were about 40% lower among older individuals given Pfizer’s BNT162b2 COVID-19 vaccine than they were in younger age groups, a concerning finding considering it’s the older individuals who are most at risk from severe COVID-19.
Is Pfizer’s COVID Vaccine Really 90% Effective?
In a Phase 3 efficacy trial, a vaccine is given to thousands of people, while researchers wait to see how many end up infected compared to those given a placebo.7 Pfizer’s Phase 3 clinical trial began July 27, 2020 and enrolled 43,538 participants8 to date ranging in age from 12 years to over 55, with a minimum of 40% of participants in the over 55 age range.9
Participants received either a two-dose series of BNT162b2, given at the 30-microgram dose 21 days apart, or a placebo. Initially an interim analysis was set to be conducted after 32 COVID-19 cases, but “after discussion with the FDA,” they increased it to after a minimum of 62 cases. According to Dr. Albert Bourla, Pfizer Chairman and CEO, in a press release:10
“Upon the conclusion of those discussions, the evaluable case count reached 94 and the DMC (Data Monitoring Committee) performed its first analysis on all cases. The case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90%, at 7 days after the second dose. This means that protection is achieved 28 days after the initiation of the vaccination, which consists of a 2-dose schedule.”
Bourla added the caveat, “As the study continues, the final vaccine efficacy percentage may vary.” In fact, there are many questions that remain unanswered regarding the reported 90% efficacy rate.
While Pfizer did release a clinical protocol of its trial,11 data for the interim analysis have not been released. "This is science by public pronouncement," William Haseltine, an infectious disease expert and former Harvard medical professor, told Business Insider.12 COVID-19 Vaccine Trials ‘Designed to Succeed’
In September 2020, Haseltine criticized COVID-19 vaccine trials, including Pfizer’s, saying their protocols reveal that they’re “designed to prove their vaccines work, even if the measured effects are minimal.”13
He points out that prevention of infection is a critical endpoint in a normal vaccine trial, but prevention of infection is not a criterion for success for COVID-19 vaccines in development by Pfizer, Moderna, AstraZeneca or Johnson & Johnson. According to Haseltine:14
“Any vaccine trial should include regular antigen testing every three days to test contagiousness to pick up early signs of infection and PCR testing once a week to confirm infection by SARS-CoV-2 test the ability of the vaccines to stave off infection. Prevention of infection is not a criterion for success for any of these vaccines. In fact, their endpoints all require confirmed infections and all those they will include in the analysis for success, the only difference being the severity of symptoms between the vaccinated and unvaccinated. Measuring differences amongst only those infected by SARS-CoV-2 underscores the implicit conclusion that the vaccines are not expected to prevent infection, only modify symptoms of those infected.”
He also explains that while most people expect that a vaccine will prevent serious illness in the event they’re infected, “Three of the vaccine protocols — Moderna, Pfizer, and AstraZeneca — do not require that their vaccine prevent serious disease only that they prevent moderate symptoms which may be as mild as cough, or headache.”15
Pfizer Didn’t Release Key Vaccine Data
While Pfizer is touting its vaccine as more than 90% effective based on 94 cases in their trial, "There are many, many outstanding questions which are left unanswered," Haseltine said.16
One of the main unanswered questions has to do with asymptomatic infections, which aren’t regularly being tested for in Pfizer’s trial. It’s possible, then, that those who have been vaccinated could still be asymptomatic carriers of COVID-19, spreading the disease to others. "That's a major point that I don't think most people appreciate," Haseltine told Business Insider. "It doesn't mean an end to the epidemic."17 It’s also unknown whether the vaccine reduced the number of cases of serious disease, hospitalizations and deaths, as no distinction was made between serious COVID-19 cases and those causing only minor symptoms.
Also missing from Pfizer’s press release is how the vaccine fared in different age groups, a key data point since older people are those most at risk of serious disease outcomes. It also remains to be seen how long any protection offered by a vaccine may last, as the study just began in July.
As for side effects, Pfizer’s Bourla said, “The DMC has not reported any serious safety concerns and recommends that the study continue to collect additional safety and efficacy data as planned.”18 Again, however, it’s far too soon to know whether the vaccine is safe. The timeline of the experimental COVID-19 vaccine is unprecedented as, on average, it can take 10 to 12 years for a vaccine to be developed and go through the normal licensing process.19
"We don't know anything about groups they didn't study, like children, pregnant women, highly immunocompromised people and the eldest of the elderly," Dr. Gregory Poland, director of the Mayo Clinic's Vaccine Research Group in Rochester, Minnesota, told NBC News.20
As for potential adverse effects, in their clinical protocol Pfizer listed the following, noting that the first five participants in each group in phase 1 would be monitored for four hours after vaccination to assess adverse effects, while others would be observed for “at least 30 minutes.”21
Injection site redness, swelling and pain
Unknown adverse effects and laboratory abnormalities associated with a novel vaccine
Potential for increased exposure to SARS-CoV-2 because of the requirement to visit health care facilities during the trial
COVID-19 enhancement, stating, “Disease enhancement has been seen following vaccination with respiratory syncytial virus (RSV), feline coronavirus, and Dengue virus vaccines.”
Coronavirus Vaccines May Enhance Disease
Even Pfizer acknowledged in their clinical protocol that COVID-19 disease enhancement is a real risk following certain vaccinations.22 In what’s known as antibody-dependent enhancement, or ADE, or sometimes called paradoxical immune enhancement (PIE). In these scenarios rather than enhance your immunity against the infection, the vaccine enhances the virus’ ability to enter and infect your cells, resulting in more severe disease than had you not been vaccinated.23
Th2 immunopathology, in which a vaccine induces a faulty T cell response, triggering allergic inflammation, poorly functional antibodies and airway damage, is another serious risk.
Both ADE and Th2 immunopathology occurred in the 1960s when a vaccination for respiratory syncytial virus (RSV) was being developed, resulting in the death of two toddlers and serious illness in several other children who received the experimental vaccine.24
Similar concerns again surfaced in testing for a potential vaccine against another coronavirus, SARS, about 20 years ago. At the time, even long-time pro-vaccine advocate Dr. Peter Hotez, dean of the National School of Tropical Medicine and professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, was shaken. According to a feature published in PNAS:25
“When SARS, also a coronavirus, appeared in China and spread globally nearly two decades ago, Hotez was among researchers who began investigating a potential vaccine. In early tests of his candidate, he witnessed how immune cells of vaccinated animals attacked lung tissue, in much the same way that the RSV vaccine had resulted in immune cells attacking kids’ lungs. ‘I thought, ‘Oh crap,’’ he recalls, noting his initial fear that a safe vaccine may again not be possible.”
Despite years of additional research and alternative development strategies, immune enhancement concerns remain, and, as explained by Robert F. Kennedy Jr. in our 2020 interview, coronavirus vaccines remain notorious for creating paradoxical immune enhancement.
mRNA Is a Novel Vaccine Technology
Pfizer’s COVID-19 vaccine is relying on novel mRNA technology that has never previously been used in vaccines.26 It essentially instructs your cells to make the SARS-CoV-2 spike protein, which is what attaches to the ACE2 receptor of the cell. This is the first stage of the two-stage process viruses use to gain entry into cells.
The idea is that by creating the SARS-CoV-2 spike protein, your immune system will be stimulated to produce antibodies, without making you sick in the process. However, another key question that needs to be answered is which of two types of antibodies are produced through this process.
Coronaviruses produce both neutralizing antibodies,27 also referred to as immoglobulin G (IgG) antibodies, that fight the infection, and binding antibodies28 (also known as nonneutralizing antibodies) that cannot prevent viral infection. Instead of preventing viral infection, binding antibodies can trigger an abnormal immune response like ADE or PIE.
In trials of Moderna’s experimental COVID mRNA vaccine, 25 participants who received two doses of its low or medium dose vaccine had levels of binding antibodies — the type that are used by the immune system to fight the virus but do not prevent viral infections — at levels approximating or exceeding those found in the blood of patients who recovered from COVID-19.29
Data for the more significant neutralizing antibodies, which stop viruses from entering cells, were reported for only eight people.
Pfizer Has $1.95 Billion Deal With US Government
While the results of Pfizer’s Phase 3 trial remain murky, as part of Operation Warp Speed the drug giant has already struck a $1.95 billion deal with the U.S. Department of Health and Human Services and the Department of Defense to provide Americans with 100 million doses of its COVID-19 vaccine after it is licensed — at no cost to recipients — with an option for 500 million additional doses.30 The agreement is part of Operation Warp Speed.
Pfizer and BioNTech also have a deal with the U.K. government for 30 million initial doses.31 The FDA’s guidance for a vaccine to receive Emergency Use Authorization requires only a median of two months of safety data following the second dose, which Pfizer expects to have by the third week of November.
At that point, they’re hoping to bring the experimental vaccine to market, with promises to produce up to 50 million vaccine doses in 2020 and up to 1.3 billion doses, globally, in 2021.32 Upon Pfizer’s announcement that their vaccine showed 90% effectiveness, shares rose 16%. The next day, CEO Bourla sold 62% of his stock, an amount worth about $5.6 million.33
Does the Pfizer CEO know something we don’t? If and when the vaccine does become available, be sure to carefully weigh the risks versus the benefits before making a choice of whether or not to receive it.
It may help in your decision to know that if you’re under the age of 40, your risk of dying from COVID-19 is just 0.01%, meaning you have a 99.99% chance of surviving the infection34 — and you could improve that to 99.999% if you’re metabolically flexible and vitamin D replete.