The US Centers for Disease Control have concluded that a third dose of COVID-19 vaccine will be needed for protection against disease, but the science says otherwise.
A review of the immune responses to infection will help explain why vaccine boosters are not needed. The graph below shows the relative concentrations of antibody and T cells (Y axis) as a function of time after first viral infection. Antibody levels and numbers of activated T cells initially rise, then decline after the primary viral infection is cleared. Reinfections at later times (years later) are marked by a rapid immune response because of the reanimation of memory cells. The host is infected, but virus is cleared rapidly and severe disease is prevented.
The same principles illustrated in this graph apply to the immune response after vaccination. After the first and second vaccine doses, antibodies and T cells are produced over the course of weeks and months and slowly decline to low but not non-zero levels. If a vaccinated individual is reinfected later, the memory B and T cells proliferate and virus-specific antibodies and T cells are produced. The memory response takes several days and therefore infection is not prevented. However virus reproduction in the immunized host is substantially reduced and severe disease does not occur. In addition, due to reduced viral replication in the face of a memory immune response, transmission is markedly reduced or eliminated. The impairment of transmission is the basis of herd immunity.
The COVID-19 vaccines were tested in phase III trials for their ability to prevent COVID-19 – a disease. They were not tested for their ability to prevent infection. Most human viral vaccines do not prevent infection, but they do prevent disease.
After multiple COVID-19 vaccines received emergency use authorization, studies in several countries were done to determine if immunity prevented infection. When the studies were done shortly after vaccination, antibody and T cell levels were high, and infection was prevented. But as the immune response waned (see figure above), vaccine efficiency against infection declined. This observation was incorrectly interpreted by many to indicate that the vaccines were failing. Largely ignored was the fact that vaccinated individuals were still protected from developing serious COVID-19 disease and death.
Recently public health officials in the US made the following statement:
“The available data make very clear that protection against SARS-CoV-2 infection begins to decrease over time following the initial doses of vaccination, and in association with the dominance of the Delta variant, we are starting to see evidence of reduced protection against mild and moderate disease. Based on our latest assessment, the current protection against severe disease, hospitalization, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout. For that reason, we conclude that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability.”
The decline of protection against infection is no cause for concern; as noted above, such a response occurs for most human viral vaccines. So that alone cannot be used to justify a third vaccine dose.
I am unaware of evidence that ‘we are starting to see evidence of reduced protection against mild and moderate disease’. Furthermore, that ‘current protection against severe disease, hospitalization, and death COULD diminish in the months ahead’ (capitals mine) cannot be used as a reason that a booster will be needed.
This week CDC released the results of two studies which demonstrate that vaccine protection against hospitalization remains strong. In one study, COVID-19 cases and hospitalizations among adults in New York were studied from May to July 2021. The results show that vaccine effectiveness against hospitalization in this state was stable: 91.9% in May to 95.3% in July. Despite increasing numbers of cases caused by the delta variant of SARS-CoV-2, hospitalization of vaccinated individuals did not increase. As would be expected as antibody and T cell levels decline, vaccine effectiveness against infection, determined by diagnostic tests, decreased from 91.7% in May to 79.8% in July.
A second study examined effectiveness of Pfizer-BioNTech and Moderna mRNA vaccines from March to July 2021 against hospitalization for COVID-19 in 18 US states. No decline in vaccine effectiveness against COVID-19 hospitalization was observed over 24 weeks: vaccine effectiveness was 86% 2–12 weeks after vaccination and 84% at 13–24 weeks.
These two studies provide no support for the need of a third vaccine dose in the US. If a third dose were given, the result would be an increase in virus-specific antibodies and T cells which might prevent infection for several months. But as antibody and T cell levels decline, which is inevitable, we would be in the same situation we are in now – infections occur but hospitalization and death is prevented. Would we then enter an endless cycle of giving boosters every 8 months? That is not a smart way to end this pandemic. Rather, measures to ensure that 80% of the population is fully vaccinated must be deployed.
The call for vaccine boosters in the US is another example of how some public health measures deployed during this pandemic are not based on science.
Note added after further thought: Sera from individuals who have been infected and subsequently vaccinated have broad neutralization activity against all known variants of concern. Whether boosting with existing vaccines could achieve similar breadth and potency is unknown but should be determined before giving millions of individuals a third vaccine dose.
CT says
Thanks very much for this, Vincent.
In relation to your comment:
“Would we then enter an endless cycle of giving boosters every 8 months? That is not a smart way to end this pandemic. Rather, measures to ensure that 80% of the population is fully vaccinated must be deployed. ”
wouldn’t it be smart if the government/health bodies or whatever worked with those who are declining the vaccine to produce and make available a vaccine, (eg one that employs older technologies), that is acceptable to the majority of those who are reluctant or refuse to have the mRNA- and DNA- based ones? (I guess that may mean putting commercial interests aside for the greater good?) Wouldn’t that be far more productive than going down the booster route?
Eric Pringle says
Hi Dr. Racaniello,
Thanks for the post. This last comment stood out to me:
“Sera from individuals who have been infected and subsequently vaccinated have broad neutralization activity against all known variants of concern.”
Very interesting stuff. Could you share a citation or two? I’d like to read more on this.
Thanks
Hal says
Vaccination season against the common flu is fast approaching. Are there any known interactions among the two vaccines?
Brian Hanley, PhD says
My objection to the current vaccines is that they are narrowly focused on spike protein. That is the protein with the highest evolutionary selection pressure for novel variants.
At least use two major proteins.
I think the big reason is that if you are doing an academic project, one protein is good enough, and it’s simpler. Add a second protein, and you have around 1.3 – 1.5 times the work to do. Make it 3, and it’s around 1.8 to 2 times. Etc.. And yes, in the small studies done on animals? Sure. That’s enough. It shows it works. But a distinction should be made between that and a real-world vaccine system.
And there’s this faction in vaccinology that doesn’t pay attention to anything but antibodies. (No virus is cleared by antibodies – it is cleared by CD8 T-cells that kill the cells infected by the virus.) And there are multiple labs and careers that have made themselves all about how to focus a vaccine so that you will almost always produce antibodies to one specific part of one specific protein. That’s why you have those papers and pop-sci articles about making antibodies to one epitope of spike protein, implying, or even saying, that all other antibodies are useless — which is just wrong. It’s not just wrong, it’s dangerous to public health.
The process of the immune system developing antibodies is stochastic. This goal of focusing is impossible to generate in all, although you can do a fair amount. But it isn’t a supportable conclusion that doing so is necessarily a good thing. Because the closer you get to that goal, the more certain you are to have a weak vaccine that the virus can escape with a few mutations — or even one mutation. And then what?
Since nobody is testing or tracking CD8 responses and what epitopes those are directed to, we can only assume that if you get your vaccine focused to one epitope mostly, that CD8’s will also be somewhat limited — until proven otherwise.
All of these vaccines are to spike. No vaccine maker has fielded a vaccine with ANYTHING except SARS-CoV-2 spike protein. So even when you get a variety of epitopes (an epitope is a subsection of the protein) that the adaptive immune system responds to, they are still ALL to parts of spike protein. Nobody appears to think about how spike is subject to the most evolutionary pressure. Why? There is no logic to this whatsoever. It’s groupthink.
Part of what we may be seeing is that there are some people that generated their immunity mostly to the section of Delta variant that changed. Immune response is a stochastic thing, and quirks of individual mutations can have interesting results. Even so, 0.6% of deaths are in vaccinated people. But Delta variant according to a recent Israeli paper is making a lot of people over 50 sick enough to require hospitalization.
The vaccine I created early last year had all 4 of the SARS-2 capsule proteins. This is not hard to do, although there are challenges when designing an RNA vaccine that uses the alpha virus RDRP gene to trigger strong interferon production. There are alternative ways to trigger interferon.
Hal says
Thanks. Has anyone studied the CD8 T cells to determine if they retain effectiveness against a variety of spike viruses during the life of an organism? Asking because I think I had the Asiatic Flu while stationed on Okinawa in 1957. Since then I have not had a head cold, only occasional sniffles, and never the sign of a flu.
Is the information in our T cells passed from mother to child?
Your average Russian guy says
To Brian Hanley: citation: “No vaccine maker has fielded a vaccine with ANYTHING except SARS-CoV-2 spike protein.”
But what about CoviVac the vaccine from Chumakov Centre? As far as I understand, it gives the most possible antibodies response than every mRNA or peptide vaccine. I am a believer in it as a booster for this fall season.
To Vincent Racaniello: I am an average guy who believes it`s okay to have a booster this fall. For now in Russia we gonna have two options: modified for Delta variant GamCovidVac (Sputnik) and CoviVac. Which is preferable to get? On the one side is a more precise weapon against current striking strain, and on the other is a more broader and universal vaccine. I don’t made my mind yet.
Sue says
Hello. Thank you for the blog. My question is;
If the covid 19 virus has been implanted in rna, then given to us, shouldn’t this change then be permanent? Why would anyone ever need a booster? It seems to me that this should only need done once. Period.
Thank you,Sue
Harry Pepe says
*Applause*
Mary says
Thank you. This is very helpful and clear.
Hal says
Again, will vaccinations for the common fall flu be recommended for those vaccinated for COVID-19, with or without boosters? And would an old bout with the Asiatic leave any immune response to subsequent exposures to other flus?
Peter Parker says
It puts the needle in it’s arm or it loss it’s job again.
Andrew Lefay says
Thank you for this blog and your videos. I find your articles fascinating but I remind myself often that I am not likely to share even a fraction of the understanding which you and your colleagues have. So please forgive this question. I am offerred a flu jab annually. It is stated that this is due to waning efficacy and mutations. I can see from several blog posts that the COVID 19 vaccines are proving effective for the variants we have encountered but I am struggling to understand how flu vaccines lose their efficacy over time but other vaccines seem to provide permanent protection. Why is this (other than the obvious need to engineer new flu vaccines due to mutations) and how does this apply in the case of COVID 19 vaccines?
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