Prior to the new covid-19 vaccines there had been no vaccines or antivirals in routine clinical use for coronaviruses. “Their development had previously been considered as low priority because the coronaviruses that were circulating in humans caused relatively mild disease; in addition, a vaccine would need to be quadrivalent – effective against 4 different viruses – and even then would prevent only a minor proportion of colds, because the majority are caused by other viruses. As such, the development of vaccines against human coronaviruses was not pursued,” explained microbiologist Florian Krammer.
A preventative for V2 would be essentially a cure for the common cold – an incredibly lucrative prospect that drug companies have rushed to cash in on. “The reason why it has been so hard to develop antiviral drugs, because almost any drug that will stop viruses dead in their tracks will also stop our cells dead in their tracks,” said immunologist Shira Doron.
Traditional vaccine development takes 15 years or more. In striking contrast, V2 vaccines have been developed in less than 6 months.
In the frenzy for V2 vaccines, makers are publicly announcing – and touting promise – when candidates trigger immune system responses. An injected organic molecule may provoke an immune response without it having any viability whatsoever as a vaccine.
American nurse Laura Minard: “Vaccines are meant to cause inflammation in the body, so that we can get an antibody response and we have no idea what that inflammatory initial response does long-term to the body. What I’m most concerned with, is there is no long-term safety profile, it’s only been 8 months.” Minard’s remarks are especially relevant considering that autoimmune response is what causes severe and long-lasting covid.
Further, the signal of severe covid disease is copious antibodies. People who are likely to develop severe covid may quickly show elevated antibody counts. Using antibodies as the indicator of potential vaccine efficacy may be grossly misleading.
Some 237 vaccines for V2 are in development in numerous countries. Already over 170 potential vaccines have proven duds. 22 vaccine candidates are at or past the human trial stage. “Historically, less than 10% of vaccine candidates that go into testing are successful,” reminds Indian doctor Soumya Swaminathan, who is chief scientist of the World Health Organization. (11 December)
All vaccines work on the same basic principle. A certain part or all of a virus is presented to the human immune system, prompting it to produce antibodies which fight against infection. Traditionally, vaccines used live, weakened forms of a virus – a technique with drawbacks which can backfire.
Other vaccine techniques avoid the use of live virus at the decided risk of being ineffective or even hazardous. It’s important to remember that severe covid disease is not from the virus per se, but from inapt immune system response. “Many of the vaccine candidates have relatively strong side effects,” observed microbiologist Florian Krammer, who has studied the V2 vaccines in development.
New genetic analysis techniques offer promise to accelerate vaccine development. But developing and testing candidates is expensive – and a risky gamble. “The reality is most vaccines will fail,” said vaccine maker Seth Berkley 4 June. And the covid-19 carrier is a novel coronavirus with considerable wiles, which means developing a vaccine for it will be an especially tricky business.
Vaccines against viral respiratory diseases are, at best, modestly effective, and only work for a short time, as viruses quickly learn how to overcome the defensive gesture. This is likely to be the case with V2, especially if antibodies are any indication – though it remains uncertain the degree to which antibodies are necessary for immunity.
Including V2, there are 5 coronaviruses in widespread circulation causing colds. “One thing we know about these coronaviruses is that people can get reinfected fairly often,” said British immunologist Stuart Neil. “The protective immunity people generate doesn’t last very long.” This has been found for covid-19 as well. “Most importantly, it puts another nail in the coffin of the dangerous concept of herd immunity,” adds British virologist Jonathan Heeney.
British vaccine developer Robin Shattock sums up the dim prospects for a V2 vaccine: “We cannot be confident natural infection will be protective for a significant proportion of individuals, nor certain of the duration of any protection. It does indicate that vaccines need to do better than natural infection. Ultimately this may require the use of annual boosting immunisations.”
Vaccine trials typically go through 3 phases. The first 2 phases test a vaccine in small numbers of people for safety and responses, including antibody production and side effects. The 3rd phase tests thousands of people to determine efficacy: whether it lowers contagion (infection rate). This matters for achieving indirect protection in a population.
Vaccines may stimulate antibodies, thus indicating to researchers a positive response. But that response may actually be wrong or suggest an ineffectual vaccine candidate. Antibodies may not neutralize V2. Antibodies may even help V2 get into cells and replicate by causing more confusion in the immune system than identification and remedy. Some antibodies have been associated with more severe cases of covid-19. Nonetheless, antibody stimulation is the metric vaccine makers have been using to deem potential efficacy and proceed to phase 3 trials.
“A vaccine can provide indirect protection even if it does not fully prevent infection. Vaccines that reduce disease severity can also reduce infectiousness by reducing viral shedding and/or symptoms that increase viral spread (e.g., coughing and sneezing). A worst-case scenario is a vaccine that reduces disease while permitting viral shedding; this could fail to reduce transmission or conceivably even increase transmission if it suppressed symptoms,” wrote American epidemiologist Marc Lipsitch and American biostatician Natalie Dean. Only the Oxford-AstraZeneca vaccine trial tested for viral load weekly regardless of symptoms. Others have not. (12 November)
A vaccine’s “efficacy” is a % reduction in disease incidence in a vaccinated group versus an unvaccinated group in a trial setting. By contrast, “effectiveness” is the ability to prevent illness among a population.
Vaccine trials are not designed, nor show, how well a vaccine may work in specific subgroups of the population. This is especially significant with covid-19, as V2 is harmless or a mild cold at worst in people in good health.
Conversely, covid presents a high risk to those with chronic health conditions, especially those in poorly health caused by an indulgent lifestyle, beginning with being overweight. If a V2 vaccine does not help this population subgroup, then the vaccine is practically worthless.
“A key limitation of observational studies is confounding. There may be many differences between individuals who do and do not get vaccinated, which may create noncausal correlations between vaccine status and outcomes. Such biases can threaten any observational study of vaccine effectiveness,” noted Lipsitch and Dean.
Covid-19 presents an especial challenge in discovering whether a vaccine is truly effective. That challenge is not even being addressed, let alone met. Predictably, statistical science has taken a back seat to profiteering.
Covid-19 is a mild cold at worst for healthy people. 90% or more of a population is exposed to V2 and never knows it. The pandemic has been a viral triumph of asymptomatic contagion.
The problem is that V2 sets unhealthy people’s immune system in overdrive – whence severe covid, which strikes just ~0.6% of the population. This is the group that a vaccine would help. Others have no need of a V2 vaccine, especially considering the risk that the vaccine itself can make you sick.
The predominant indicator of covid-19 risk is being overweight and attendant illnesses, such as diabetes. Some 80% of Americans and Brits fall into this category, yet only a minuscule percentage of them are suffering from covid beyond having a typical cold. Though commonly identified, age is a scant indicator of covid risk.
In a vaccine trial, half the participants get the candidate vaccine, while the other half – the control group – get a placebo. Placebos are significant in that the placebo effect is well documented as helping thwart sickness.
Because of the unique nature of covid-19, in that V2 seldom causes sickness, and risk groups are identifiable, it is imperative to have the vaccinated group be equivalent to the control group. Vaccine makers are not doing this. Instead, they are using false risk factors, especially age rather than fattiness. By this alone the vaccine trials are a sham: in not having equivalence between those vaccinated in a trial and the control group.
The error in the outrageously high efficacies being reported by vaccine makers lies in their statistical butchery. The proper statistical method of efficacy is to compare outcome percentages of all participants. Instead, vaccine makers are comparing the numbers of those that get sick with covid in each group, ignoring the side effect sicknesses of those in the vaccinated group.
Out of tens of thousands of vaccine trial percentages, makers are reporting efficacies of 90% or more based upon a very few people – a dozen or less – getting sick after getting the vaccine. Such numbers are so low that they are statistically insignificant.
There is a direct analogy of the danger in not taking proper sample size in considering risk. The US space shuttle Challenger spectacularly blew up 73 seconds after launch in 1986, instantly killing everyone on board. The cause was the failure of the O-rings which sealed segments of the launch rockets. The O-rings failed from cold weather.
Decision makers at NASA had relied upon an analysis which showed no apparent relationship between air temperature and booster rocket segment seals. But the sample set was incomplete. It failed to include all launches involving no damage – launches which were mostly made at higher temperatures. A plot of all data showed a clear correlation between low temperature and O-ring damage.
Vaccine makers are making the same statistical mistake as NASA did in 1986: using a cherry-picked sample set and ignoring side effects to make patently false claims. Outsiders, including those in government, are too ignorant – and desperate – to do anything but willingly be duped.
The political pressure to make any vaccine available is enormous, as is the profit potential for vaccine makers. Countries around the world have made deals with drug-makers for any vaccines that even look like they will pan out.
“The vaccines coming through fastest are the most experimental. It is possible they won’t be all that great and that others – created using more tried-and-tested but slower methods – might be better,” said British immunologist Adam Finn. “But to prove that point will become very difficult if lots of individuals have already been given the first vaccine. It will need vast numbers of people to demonstrate which is best or if a different vaccine is more suitable for particular groups, like the elderly. If we get a vaccine that works, but not very well, it’s almost worse than not having one at all because it gets in the way of getting a better vaccine.”
5 million Chinese have already gotten the vaccine by Sinopharm, a China state-owned company. Another efficacious vaccine from China is by Sinovac Biotech. The vaccines by Sinopharm and Sinovac are traditional inactivated virus vaccines. “Inactivated vaccines are one of several tried-and-true approaches,” remarked Nicole Lurie, American epidemic analyst. There has not been a single report of severe adverse reaction with the Sinopharm or Sinovac vaccine. These vaccines are showing around 50% efficacy, which is not especially encouraging.
The level of antibodies the Sinovac and Sinopharm vaccines produce are somewhat less than in people who have just recovered from covid, or those who have taken vaccines by Moderna or Pfizer. That may not have any significance. Inactivated virus vaccines produce broader antibody and T cell responses, because they contain the full set of viral proteins, rather than a single one such as the spike.
The Sinopharm and Sinovac vaccine are administered in 2 doses. Unlike the mRNA vaccines by Moderna and Pfizer, which need to be kept at extremely low freezing temperatures for storage, the Sinovac vaccine only needs to be refrigerated.
Russia is using a domestically developed, traditional inactivated virus vaccine dubbed Sputnik V. Sputnik V is a 2-dose vaccine that needs only near-freezing refrigeration.
The covid vaccines developed in Russia and China are based on a modified form of adenovirus type five (Ad5), which “a lot of people already have immunity to” said vaccine researcher Anna Durbin.
Thai virologists at the startup firm Baiya Phytopharm developed a V2 vaccine by integrating the virus’s DNA into tobacco leaves. The plant responds to the DNA and produces proteins about a week later. The vaccine has proved successful on monkeys. The firm is now seeking funding for human trials. (15 December)
Oxford-AstraZeneca have been testing a 2-dose vaccine via a weakened common cold virus (adenovirus). They accidentally discovered, during a phase 3 trial, that the vaccine with half of the originally recommended first dose works better than 2 full doses. Such serendipity discourages the impression of competence, to be sure. A new trial with altered dosage is planned. (26 November)
“It would be madness to use more vaccine than you needed to get less efficacy,” said British immunologist Katie Ewer. In light of the Oxford finding, immunologists speculate that a lower 1st dose works better in priming memory immune cells. Which is to say that the dosages of covid vaccines are likely to be a crap shoot with regard to optimality, especially in light of the rush to get them out. (26 November)
Oxford-AstraZeneca finally made some data on their vaccine trial publicly available Tuesday 8 December. “The press release raised more questions than it answered,” said American microbiologist John Moore. “I just can’t figure out where all the information is coming from and how it’s combining together,” said American biostatistician and vaccine trial designer Natalie Dean. Oxford-AstraZeneca “get a poor grade for transparency and rigor when it comes to the vaccine trial results they have reported,” she added. Oxford-AstraZeneca used pooled data in coming to their efficacy conclusions: an invalid statistical technique.
AstraZeneca had previously failed to notify the US FDA that it had halted its trial because of a mysterious illness. Dr. Eric Topol, a vaccine clinical trial expert, said, “If they just were upfront on safety, on efficacy, on dosing, on everything, from the get-go, they’d be in such a better position. But what they’ve done now is diminish credibility, and I don’t know how they’re going to regain that.” (9 December)
US drug makers Pfizer and Moderna have vaccines which use messenger RNA (mRNA), a new technology that previously had never resulted in a vaccine. These vaccines only present the protein spike of the virus to the immune system, thus cheating the immune system of making its own evaluation on how to recognize the virus.
German drugmaker BioNTech developed the Pfizer vaccine. There were 20 initial vaccine candidates. 5 were initially tested. Only 2 strongly provoked the immune system. Of the 2, the vaccine declared successful was the one with fewer side effects.
Pfizer announced Wednesday 18 November that analysis of its phase 3 vaccine trial of 41,135 participants suggested a vaccine that was 95% efficacious – an outright statistical lie. Only 8 people got sick after getting the vaccine, out of 170 total (vaccinated or not) who got sick. In cases where severe covid occurred, 1 in 10 got the vaccine. The Pfizer trial data has yet to be peer reviewed. Because some 95% of V2 infections in healthy people only cause mild to moderate covid symptoms at worst, this shows that Pfizer’s vaccine candidate may be as bad or worse than being infected with V2. (18 November)
Well into its mass vaccination campaign using the Pfizer jab, Israel discovered that the Pfizer vaccine is not nearly as effective as advertised. (19 January)
Especially considering the wide-ranging symptoms covid-19 can cause, vaccine side effects may be an ongoing issue. In 1976, for instance, the “swine flu” vaccine caused an otherwise rare condition – Guillain-Barré syndrome – in which the immune system attacks the nervous system. The problem did not become obvious until the vaccine had already been injected into 45 million Americans.
mRNA vaccines are known to be prone to side effects not seen in traditional vaccines using inactivated viruses. Sickness side effects from the Pfizer-BioNTech vaccine include headache, fatigue, fever, and worse, are being reported in a small percentage of vaccinated people. Dr. June Raine, head of Britain’s vaccination program, said “by the law of averages, some people will be sick or even die after they’ve had the [Pfizer/BioNTec] vaccine” that is being used against covid there. People are having allergic reactions to the Pfizer vaccine. Ugur Sahin, chief executive of BioNTech, admitted that side effects were an issue.
Moderna said most side effect reactions were mild to moderate and short-lived. Among the reported side effects were injection site pain in 2.7% of trial volunteers after the 1st jab. After the 2nd, the most significant side effects included fatigue in 9.7%, muscle pain in 9% and joint pain in 5%. Others had headaches, other pains, or redness at the injection site. These side effects are as bad or worse for healthy people than catching covid, which has gentler viral loading than being shot twice with concentrated immune system provocation. People are reporting worse side effects after the 2nd dose of the vaccine.
British pharmacoepidemiologist Stephen Evans: “Allergic reaction occurs with quite a number of vaccines, and perhaps even more frequently with drugs.” Severe allergic reactions have been notably high with the Pfizer vaccine.
In deciding whether to get vaccinated, side effects are a tradeoff risk to consider, especially with V2, which many people are infected with and never know it, and is a mild cold at worst for generally healthy people.
The messenger RNA vaccines developed by BioNTech/Pfizer and Moderna must be frozen at low temperatures prior to being administered. This freezing requirement, along with the need for 2 doses, poses logistics problems: putting it out of reach for some 2/3rds of the world’s nations, and problematic for any country. Just days after Pfizer jabs started to be given in the last week of December 2020. Germany’s vaccination campaign faced delays in several cities after medical staff found potential irregularities in the cooling of the Pfizer shot. The US has also had vaccine spoilage problems.
Between the two mRNA vaccines, Moderna has the more stable one. Whereas the BioNTech/Pfizer shot must be kept between -70 °C and -80 °C from production facility to patient, Moderna’s vaccine, though normally needing to be frozen at -20 °C, may be kept at 2 °C to 8 °C for 30 days, and will last 12 hours at room temperature.
Moderna announced Monday 16 November that its phase 3 trial had shown its mRNA vaccine had a 94.5% efficacy. This percent was based on 90 patients receiving a placebo while 5 got the vaccine – a tiny number to boast such a claim. The 95 participants in the Moderna analysis included 15 adults aged 65 or above, and 20 participants from diverse races, including 12 identified as Hispanic, 4 African Americans, 3 Asian Americans and 1 multiracial person. Moderna said the vaccine appeared equally safe and effective in all the subgroups. In the rush to cash in, Moderna went ahead and requested approval for its vaccine before completing its phase 3 trial.
British virologists discovered a new variety of V2 in south England (where London is located). The Guardian reported 15 December: “The new variant has multiple mutations in the spike protein, the most troubling of which appears to be what scientists call a deletion – in this case, the loss of 2 amino acids from the spike protein – which may make it spread more easily. The same deletion had been spotted in coronaviruses in several countries since the spring, but at low levels. It began to take off in southern England in August and September.”
The deletion was spotted in a patient with a weak immune system at Cambridge who was treated with blood plasma from a recovered covid patient: an experimental technique that had been found somewhat effective in providing antibodies. V2 evolved the deletion “mutation during that treatment and may have become more resistant to the antibodies. The patient ultimately died from the infection,” The Guardian continued. “We think that’s a mechanism for the virus to start escaping,” said Cambridge microbiologist Ravi Gupta.
The new V2 variety spotted in England is 70% more contagious than the previous variety. Another, also more infectious variety, has been identified in South Africa. V2 has proven itself a saltational virus: one capable of rapid, intelligent adaptation.
mRNA vaccines, like those from BioNTech/Pfizer and Moderna, may become ineffectual sooner because they only present the immune system with the V2 spike protein, not the whole virus, as traditional vaccines – like those made in China – do. What is called “vaccine escape” may be easier against mRNA spike-only vaccines because the immune system was not given the opportunity to do its own recognition analysis. Instead, mRNA vaccine developers substituted their guesswork as to what the immune system should think significant.
At $50 to $60 US for a course of 2 shots, Moderna’s vaccine is more expensive than the other front-runners. AstraZeneca and Oxford University are aiming to sell their vaccine at $4 a dose.
While studying dengue fever, American virologist Soctt Halstead noticed in 1977 that antibodies themselves made for greater sickness upon a 2nd exposure to the disease. The effect was called antibody-dependent enhancement (ADE). ADE “is a genuine concern,” says British virologist Kevin Gilligan. “Because if the gun is jumped, and a vaccine is widely distributed that is disease enhancing, that would be worse than actually not doing any vaccination at all.” Unexpected glitches like ADE are the kind of problems vaccine developers look for in phase 3 testing of vaccines: the final testing phase that has been skipped or abbreviated in the rush for a covid-19 vaccine.
The likelihood is that a V2 vaccine will be marginally effective, cause health complications in some small percentage of the people getting it, and lose what efficacy it had within a year. A cure for this cold is not going to be had in the rush that characterizes this vaccination crusade.
Another salient point is that a viable V2 vaccine will be thwarted in fat people. Obesity compromises the immune system. Therefore, a V2 vaccine won’t help those most at risk of severe covid.
“Virus biology and vaccines technology could be the limiting factors, but politics and economics are far more likely to be the barrier to immunization,” explains American public health researcher Jonathan Quick. The final hurdle is getting the vaccine to all those who need it. This is a challenge beyond sheer logistics, as plutocratic mechanics are inherent in all political institutions. Mass vaccination is a costly proposition. During the 2009 H1N1 flu pandemic, vaccine supplies were snapped up by rich nations, leaving poorer ones short.
Unsurprisingly, a small group of wealthy countries has bought more than half of the expected supply of the most promising vaccines. Nearly 2/3rds of the world’s population will not have a vaccine until at least 2022.
In an alliance led by the World Health Organization, 156 countries have joined a global scheme intended to ensure fair distribution of vaccines against covid-19. China has joined, and will offer its vaccines. The curmudgeonly US has not.
Ishi Nobu, “Covid-19 Pandemic: Daily World Report,” which has the latest covid vaccine news.
Ishi Nobu, “Covid-19“.
Ishi Nobu, “Coronaviruses & CoV2“.
Ishi Nobu, “NASA’s Challenger,” The Echoes of the Mind (2019).