The Moderna and Pfizer mRNA vaccines, which are likely to be available within the next 1-3 months, have been successfully tested in non-human primates and humans. In the non-human primates, the vaccine appears to stimulate the formation of antibodies that inhibit viral replication and prevent symptomatic Covid-19 disease in animals exposed to the virus. Human clinical trials also appear successful with a ten fold smaller incidence of symptomatic Covid-19 infections in vaccine recipients as compared to a placebo group. At this time, no severe adverse events have been reported in vaccine recipients.
There is good reason to believe that the vaccine will confer immunity for at least several months, and possibly years, for almost all recipients including those over age 70.
There is no evidence that I am aware of at this time that the vaccine poses any long term danger to its recipients.
Most of what follows is based on data from the Moderna vaccine and its trials. I think it’s most likely that this vaccine will be more widely available than the Pfizer vaccine given that it can be stored at temperatures achievable by many freezers, whereas the Pfizer vaccine is currently said to require temperatures far colder.
I’ll also say at the outset, I am not an expert in infectious disease or in vaccines. I have done my best to understand and organize publicly available information. My references are listed at the bottom of the page. Please contact me if you have any questions or corrections.
How does it work?
The Moderna and Pfizer vaccines are mRNA vaccines. This vaccine technology is not a brand new idea, but it’s my understanding that this will be the first time it is used in humans for an infectious disease.
The vaccine is a solution composed of messenger RNA (mRNA) inside of lipid nanoparticles and then diluted in sterile saline solution (i.e. salt water). The vaccine is injected into the muscle, and the lipid nanoparticles are taken up by muscle cells. Once in the cell, the mRNA is translated into a protein.
You can see an animation of mRNA translation in this Youtube video.
The vaccine mRNA contains the genetic code for a slightly modified version of the SARS-Cov-2 spike protein (the protein that’s responsible for binding to the ACE2 receptor on our cells in order to gain entry and cause infection). In essence, the vaccine causes our own cells to manufacture a viral protein, which can then be recognized by our immune system. Immune cells then create new antibodies (which are also proteins), that recognize the viral protein. When an individual with antibodies encounters the actual virus, the antibodies bind to the virus and tag it for destruction by immune cells. This is the primary means by which the Moderna mRNA vaccine will generate immunity — by generating antibodies*. It also appears that there may be some T-cell mediated immunity from vaccination as well.
This particular vaccine requires two injections (3 or 4 weeks apart from one another) to ensure that a sufficient quantity of neutralizing antibodies are produced. Though it’s possible that some individuals will have sufficient immunity from a single dose, you won’t know it, and thus it’s likely that two doses will be recommended for all recipients.
Is it safe and how do we know?
The Moderna vaccine has been in development since January, and has been given to a diverse population of over 30,000 participants in clinical trials since March 16, with no severe adverse events documented thus far.
The manufacture of the first clinical batch was completed on Feb 7, 2020. The first participant in the first phase of clinical testing was dosed on March 16, 2020. On May 29, the second phase of clinical testing resulted in the recruitment of 300 people age 18-55, and another 300 over age 55. Phase three is a randomized placebo-controlled study of 30,000 participants over age 18, enrollment of which was completed on October 22, 2020. More than 7,000 of the participants are over age 65; 5,000 are under age 65 but have significant comorbid conditions (e.g. diabetes, obesity, cardiac disease); 11,000 participants are from "communities of color," with 6,000 who "identify as Hispanic or LatinX,"; and over 3,000 who "identify as Black or African American."*
One safety concern is the interaction of the vaccine with the immune system. Explicitly, some are concerned that antibodies produced as a result of vaccination could cause a subsequent Covid-19 infection to actually be more severe. One way this could happen is through a syndrome called "vaccine associated enhanced respiratory disease" (VAERD).
VAERD occurs when a vaccine recipient makes antibodies that bind to a viral protein, but that do not fully neutralize the virus. In this case, the virus, now bound to this antibody, could "hyper-activate" the immune system, so to speak. This "hyper-activation" could cause a more severe response to viral infection than would have occurred without vaccination.
According to researchers, this risk has been mitigated by ensuring the antibodies produced by vaccine recipients are "potently neutralizing," and that Th2-biased CD4 T-cell responses are avoided.*
Is it effective and how do we know?
It appears that the vaccine is highly effective at preventing Covid-19 infection.
At a dose of 100 mcg, after 8 weeks, non-human primates were exposed directly to virus by the intranasal and the intratracheal route. This means that animals were given doses of virus into their noses and lungs. Seven days later, there was no measurable viral RNA or viral antigen within the respiratory tract of the vaccinated animals. The animals were then sacrificed. Researchers examined their lungs for signs of infection and inflammation – none was found. This means that vaccinated animals were able to clear the virus from their noses and lungs rapidly after exposure and that the virus did not leave any evidence of damage in its wake.
In addition to this animal experiment, human clinical trial data shows that neutralizing antibodies are produced in amounts equal to or greater than that produced by natural infection. This response was seen across age groups, including recipients over age 70 (the vaccine has not been tested in people under age 18).
Furthermore, in ongoing clinical trials, roughly one tenth of vaccinated humans have developed symptomatic Covid-19 infection in comparison to the placebo group.
Will it prevent transmission?
It will probably attenuate transmission significantly. It appears that viral replication in the nasopharynx is diminished in vaccinated non-human primates, suggesting that the vaccine may be very helpful in limiting transmission for at least three reasons: i) decreased viral replication, ii) decreased duration of viral carriage, iii) decreased number of infected individuals in a vaccinated population at a given time.
What are the "side effects," from vaccination?
Based on phase 2 data, it appears as though many recipients will have at least one "mild," or "moderate" symptom from vaccination. The reported symptoms will be familiar to almost everyone: headache, myalgia (i.e. body or muscle aches), arthralgia (i.e. joint aches), injection site pain, and fatigue. Very few recipients had fever or chills.*
I have seen anecdotes that the reaction to the second dose of vaccine in particular may be more significant than most people are accustomed to feeling with familiar vaccines such as the flu vaccine.
Will the vaccine be useful in those previously infected with Covid-19?
I haven’t seen any data or expert commentary to support this one way or the other. However, quantity of neutralizing antibody seems to be significantly higher in vaccine recipients compared to post-Covid patients who donated convalescent plasma. There has also been evidence of waning immunity months after infection. Thus, it follows that vaccination might be beneficial even for those previously infected.
Furthermore, researchers surmise that vaccination will confer improved immunity as compared to natural infection for several additional (and highly technical) reasons that you can read about here.
What is the onset and duration of immunity?
Based on animal and human data, a vaccine recipient will likely develop immunity by 6 or 7 weeks after the first of two injections* is administered. The duration of immunity (i.e. the period of time that a vaccine recipient will be immune after vaccination) is currently unknown, but based on antibody data from natural infection, it’s reasonable to assume that vaccine generated immunity will last at least three months, but probably much longer (perhaps a year or two according to some experts). There are several reasons to believe that vaccine generated immunity will be more potent than immunity from natural infection.
Will I be taking it?
I will most likely take the vaccine, but not until at least two months after the vaccine has been rolled out.
I am adopting this strategy based on the interview of Paul Offit, MD, who appeared on Peter Attia’s Podcast several weeks ago. As an infectious disease and vaccine expert, and member of the FDA advisory board for the Covid-19 vaccine, Paul pointed out that for serious vaccine side effects that have occurred with other vaccines – Polio, Flu, Measles, and Yellow Fever vaccines – the severe adverse effects were discovered within two months of vaccine availability, but not before.
I highly recommend listening to Peter Attia’s podcast episode featuring Paul Offit, MD. In the interview, he provides fascinating historical context and detailed information about Covid-19 vaccination.
If I were at higher risk for severe Covid-19 (i.e. over age 65 and/or suffered from comorbid conditions such as diabetes, hypertension, obesity, etc), then I may be more likely to take the vaccine as soon as humanly possible.
“#137 – Paul Offit, M.D.: An Expert Perspective on COVID-19 Vaccines.” 2020. Peter Attia. November 16. https://peterattiamd.com/pauloffit/.
“A SARS-CoV-2 MRNA Vaccine — Preliminary Report.” 2020. New England Journal of Medicine 383 (12). Massachusetts Medical Society: 1190–92. doi:10.1056/NEJMc2026616.
Anderson, Evan J., Nadine G. Rouphael, Alicia T. Widge, Lisa A. Jackson, Paul C. Roberts, Mamodikoe Makhene, James D. Chappell, et al. 2020. “Safety and Immunogenicity of SARS-CoV-2 MRNA-1273 Vaccine in Older Adults.” New England Journal of Medicine 0 (0). Massachusetts Medical Society: null. doi:10.1056/NEJMoa2028436.
Corbett, Kizzmekia S., Barbara Flynn, Kathryn E. Foulds, Joseph R. Francica, Seyhan Boyoglu-Barnum, Anne P. Werner, Britta Flach, et al. 2020. “Evaluation of the MRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.” New England Journal of Medicine 383 (16). Massachusetts Medical Society: 1544–55. doi:10.1056/NEJMoa2024671.
Jackson, Lisa A., Evan J. Anderson, Nadine G. Rouphael, Paul C. Roberts, Mamodikoe Makhene, Rhea N. Coler, Michele P. McCullough, et al. 2020. “An MRNA Vaccine against SARS-CoV-2 — Preliminary Report.” New England Journal of Medicine 383 (20). Massachusetts Medical Society: 1920–31. doi:10.1056/NEJMoa2022483.
“Moderna.” 2020. In Wikipedia. https://en.wikipedia.org/w/index.php?title=Moderna&oldid=991237125.
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