Vaccines 101

Warning: This blog is sciencey


As the US races past 0.1% of the population dying of COVID-19, help is on the horizon in the form of shots in arms. With two vaccines being widely distributed in the US and more on the way, one can be hopeful we will conquer this virus soon and get back to our normal lives. This article will focus on vaccines available or soon-to-be available in the US. Additional and/or different vaccines are available in other countries.


SARS-CoV-2, the virus causing COVID-19, is an RNA virus. Such viruses are known to mutate frequently. Vaccines against SARS-CoV-2 are aimed at raising an immune response against the virus’s spike protein, with some eliciting a response against other parts of the virus, too. The spike protein, made of 1273 amino acids, is distributed around the viral surface and attaches the virus to receptors on human cells, allowing the virus to enter. The general thinking is that since binding of the spike protein to specific human cell receptors is crucial to the virus’s infectivity, it is unlikely to remain infective if the spike protein mutates significantly, especially in the region that actually attaches to the human receptor.


If you’ve been trying to keep up with vaccine development in the news, you have probably heard about the different kinds of vaccines. Many are in the pipeline in various countries. Below is an overview of the main types of vaccine platforms, or types:


Nucleic acid vaccines (These are very new and had not been distributed to humans prior to the current RNA vaccines in use.)


Messenger RNA vaccines: Both the Pfizer BioNTech and Moderna vaccines use messenger RNA (mRNA) manufactured in the laboratory, then suspended in a lipid coating. The latter protects the mRNA from degradation as it makes its way into the vaccine recipient’s cells. Once inside the cell, the mRNA directs the cellular machinery to make the protein the mRNA instructs it to make—the viral spike protein. Well, almost the spike protein. Due to instability of the viral spike protein in suspension, the vaccine mRNA codes for a protein almost identical to the SARS-CoV-2 spike protein, but substitutes two amino acids to enhance stability. The vaccines produced by the two companies appear to use the same mRNA, although the lipid coatings are different. As the body produces many copies of the modified spike protein from the vaccine mRNA, an immune response is mounted.


DNA vaccines: These are limited as they need special modes of delivery so the DNA can reach the cell’s nucleus where it can direct the production of protein molecules. DNA vaccines tend to be less potent. A vaccine against COVID-19 using this technology is being studied by Inovio Pharmaceuticals together with the International Vaccine Institute in South Korea.


Viral Vector vaccines (These are fairly new.)

These vaccines use harmless viruses (vectors) in which a component of a pathogenic virus has been added to raise an immune response against the pathogenic virus. COVID-19 vaccines of this sort use harmless viruses carrying the COVID-19 spike protein. The Oxford-AstraZeneca vaccine, which may be approved for use in the US soon (and is currently being administered in the UK, India, Mexico, and several other countries), and the Johnson and Johnson vaccine (in trials now) are viral vector vaccines. Chinese and Russian vaccines also use this type of platform.


Acellular vaccines (These are fairly new)

This type of vaccine is made from a component of the pathogenic virus. The Novavax vaccine uses the spike protein of the SARS-CoV-2 virus having the same changes introduced in the mRNA vaccines, but with additional alterations to render it more stable.


Traditional:

Inactivated virus: These vaccines are made of chemically inactivated, non-replicating pathogenic viruses. (These are being developed in India, China, and Kazakhstan).


Live attenuated virus: Genetically weakened forms of a pathogenic virus are used. These vaccines can be given intranasally to induce a mucosal immune response. Several for COVID-19 are in preclinical development.


Virus-like particles: Viral protein(s) such as the spike protein, are incorporated into virus-like particles.

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Now a word about clinical trials. These are highly regulated procedures whereby the safety and efficacy of vaccines and medications are tested. Clinical trials progress through phase I, phase II, and phase III. This happens after preclinical evaluation, which includes animal testing. Completing each phase typically takes several years, but the timeline was significantly shortened for the development of the COVID-19 vaccines. Below are brief descriptions of what the different phases are in terms of vaccines.


Phase l: A small number of healthy volunteers (usually <100) is given a low dose. If that dose is found to be safe, other subjects are tested with increasing doses as safety allows. Minimal data regarding efficacy is collected. This would likely include information on the production of neutralizing antibodies and T-lymphocyte response, thought to be important in protecting against COVID-19.


Phase ll: This usually involves several hundred people. More safety information, and data regarding the immune response are collected.


Phase lll: This involves a large number of people who receive the vaccine or a placebo. Safety information is collected, and the vaccine efficacy is calculated. In case you’re wondering how vaccine efficacy is calculated:


Efficacy =

[(attack rate in unvaccinated - attack rate in vaccinated)/(attack rate in unvaccinated)]x 100


Example:

100 people in the unvaccinated (control) group and 100 people in the vaccinated group are followed.

25 unvaccinated people get the disease, while 2 vaccinated people get the disease.

Efficacy = [(25-2)/25] x100= 92%

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The data on the new vaccines is all preliminary due to the limited number of people studied, and lack of long-term follow-up. Conclusions will be adjusted over time as warranted.


Vaccines are recommended for people who have recovered from COVID-19. Due to lack of data, COVID-19 vaccination within two weeks of another vaccine is not recommended.


What we know (by the time you read this, some information may be out of date):

The Pfizer/BioNTech vaccine:

Two doses, given 21 days apart.

Age 16 and older are eligible.

95% effective 7 days after 2nd dose.

Patients older than 65 have a slightly lower antibody response.

Side effects are less in people over 55 years of age.

2 weeks after the first dose, the rate of infection in vaccinated people starts to decrease relative to those who received a placebo (52% efficacy).

For those who do contract the disease, there appears to be reduced risk for a severe outcome.

The Moderna vaccine:

Two doses, given 28 days apart.

Age 18 and older are eligible.

94% effective 14 days after 2nd dose

For adults 65 and older, the vaccine is 86% effective.

Side effects are less in people older than 65 and in those with previous COVID-19 infections.

Vaccine efficacy from a single dose is 80%, with a mean follow-up of only 4 weeks. Data suggests there is a reduction in asymptomatic infections between dose 1 and 2.

For those who do contract the disease, there appears to be reduced risk for a severe outcome.

Oxford/AstraZeneca vaccine:

70% efficacy 14 days after 2nd dose

Strangely, a subgroup receiving a lower 1st dose had 90% efficacy, but this may not be statistically significant.

There was one possible significant side effect.

Janssen (Johnson and Johnson):

This will probably be given as a single dose, although the effect of a 2nd dose is being studied.

Age 18 and older are being studied.

Recently released data indicates the vaccine is 85% effective in preventing severe disease 28 days after a single vaccination, and 100% after 49 days.

Side effects are lower in people older than 65.

Novavax:

Clinical trial in UK: almost 90% efficacy.

Clinical trial in South Africa: just under 50% efficacy.

Almost all the positive cases were caused by the new South African variant.

Many trial participants infected with the new South African variant had previously tested positive for COVID-19.


What we don’t know:

These vaccines haven’t been tested on children. However, clinical trials are underway on older children and, if found to be safe, will be performed on younger children.


These vaccines haven’t been tested on pregnant women. Studies are being planned, starting with women in the second and third trimesters.


Can you get COVID-19 twice? Probably, but only rarely (this may not hold for the South African variant).


How long are you immune after infection or immunization?


Is a booster needed? If so, what would be the best timing for that?


We don’t have hard numbers on the chances of serious illness or death following one or two vaccinations.


How many vaccinated people are asymptomatic carriers (contagious) after one or two doses? This will affect the impact of vaccination on community transmission. Until we know, it appears prudent to enforce mask-wearing, even among those who have been vaccinated.


What is the long-term efficacy of only 1 dose of vaccines now requiring two doses? (Most people in studies received a 2nd dose.)


Will vaccines be effective against new variants? The South African variant is currently the most worrisome. It has multiple mutations, some of which change the shape of the virus surface and thereby weaken the effectiveness of vaccines. A recent study by Pfizer indicates the South African variants has only a small impact on the effectiveness of the antibodies produced by their vaccine. I don’t know the details of the study, or what the “small impact” was. Experts believe that if the efficacy of an mRNA vaccine is significantly reduced by a viral mutation, they will be able to quickly manufacture a slightly tweaked booster to increase potency.

The Novavax vaccine efficacy is significantly decreased in the South African variant. Preliminary studies regarding the Johnson and Johnson vaccine indicate it is very effective in preventing severe disease from the South African variant. This may not hold up as more data is collected.

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The pandemic has given us a peek at the complexity of vaccine production and distribution.


Many in the public were amazed that vaccines against COVID-19 were produced so rapidly. This is not completely without precedent. After all, a vaccine against the Zika virus was produced in approximately 7 months by Inovio Pharmaceuticals. There was much less hoopla about that, as by the time the vaccine was made, the Zika virus no longer posed a major threat. The usual exhaustive clinical trials required before marketing a vaccine weren’t done with the Zika vaccine, and still haven’t been completed. There is so little disease caused by the Zika virus now, phase III clinical trials aren’t possible unless volunteers are purposefully infected.


Let’s not forget that the rapid development of the current vaccines is due to the hard work of dedicated scientists. Only after years of basic science research laying foundations for more patient-oriented research, were the pieces in place to rapidly produce much-needed vaccines. This includes the ability to sequence the nucleic acids that form the core of viruses, and the ability to produce specific proteins and nucleic acid segments at will (check out some of this technology in my recently published novel, Unnatural).


It is important to note that Chinese scientists had completely sequenced COVID-19 RNA early in 2000, and shared the information with the world. That gave vaccine manufacturers a leg up in producing vaccines using the various platforms available. Vaccines targeting the spike proteins of related viruses (SARS-CoV-1 and MERS) had already been developed, further facilitating development of vaccines for COVID-19. (Human trials for these earlier vaccines were halted when the diseases they protected against decreased significantly.)


COVID-19 vaccine production was expedited by increased collaboration between governments, regulatory authorities, and the scientific community around world. Governments (including the US, the UK, Canada, Belgium, Switzerland, Norway, Germany, and the Netherlands), charities, and Big Parma invested billions of dollars into research and simultaneous (rather than sequential) industrial “scaling up” to mass produce vaccines before they were developed.


The two COVID-19 vaccines currently being distributed in the US were approved for emergency use, eliminating the long wait the FDA usually requires before allowing a vaccine to be widely delivered. Not only was the follow-up time shortened significantly, but the time it took to get a sufficient number of positive cases in the control group after the vaccine was given was much less than expected due to the soaring infection rate.


I hope you can get your vaccine soon if you haven’t already. You probably won’t have a choice, but whichever vaccine you are offered in the US, I’m confident it will be safe. I’m not so sure about the Russian or Chinese vaccines.


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