First, we lay the groundwork for the concept of a three-dose Covid-19 vaccine. Many of the vaccines that are part of our routine immunization program in the United States are three-dose or more. Hepatitis B, rotavirus and HPV vaccines are delivered in three doses, usually with the first two doses together and the third with a few months.
Other vaccines, such as diphtheria, tetanus, and polio, are four or more doses. Despite the new delivery system for CovR vaccines with mRNA, it is now clear that their potency decreases over time, as with most conventional vaccines. Therefore, the fact that our understanding of vaccine-induced Covid immunity has led me to the conclusion that we need a third dose should come as no surprise.
What remains to be fully understood is whether three doses will suffice. Science is not static and our determination of what it takes to protect ourselves from SARS-CoV-2 will change as our understanding of the virus evolves. But if we look at what we know today about the virus and our natural, vaccine-induced immunity, we probably need additional shots.
I wouldn’t be surprised to see annual or semi-annual features of Covid-19, at least over the next few years. The reason for this is not due to the failure of vaccines, but to the nature of the virus.
Coronaviruses, like influenza viruses, are masters at eluding the immune system. Its ecological niche is found in long-lived animals with competent immune systems. These animals have usually been infected many times by the virus’s own predecessors. Think about the annual waves of flu infections and you will have a pretty clear picture of what we could depend on with SARS-CoV-2.
Contrary to many people’s beliefs, vaccines do not form an impenetrable shield. Rather, vaccines trigger memory that allows the immune system to respond quickly and infect infections into the outbreak before the virus has a chance to spread to the body.
What we don’t know exactly, but we suspect, is that you need a certain level of neutralizing antibodies to stop replication and that the time frame to stop that replication is likely to be short. This is based on our understanding of the nature of the virus and immune suppression.
To finish turning it into a fast coating: SARS-CoV-2 can deactivate our body’s ability to generate an innate immune response, which means that, for its protection, vaccine-induced neutralizing antibodies must of being meaningful and powerful.
SARS-CoV-2 acts on multiple levels to counteract innate immunity. As a result, a few hours after infection, most of the proteins produced by the cell are viral, allowing more viral particles to circulate between the surrounding cells. In addition, SARS-CoV-2 suppresses signals that can activate an immune response. In this way, alarms are prevented from sounding inside our bodies, which generates more time to reproduce the virus at high concentrations.
High levels of anti-SARS-CoV-2 neutralizing antibodies can elude these immune suppression mechanisms by binding to the virus and preventing it from binding to other healthy cells. There is no magic number in terms of the levels of neutralizing antibodies needed for immune protection. But immunity studies, both from a previous infection and stimulated by a vaccine, suggest that the more antibodies you have, the better.
If the virus has tools to help it stealthily disarm our immune system, what better way to suffocate it than with a wave of antibodies that leaves no room for surprises?
This brings us back to the idea of a booster vaccine. Israel is the case study. It was the first country to vaccinate most of its citizens against Covid-19. By the end of March, more than half of the population had received two doses of highly effective mRNA vaccines. In June, all national restrictions, including internal masking, were removed, and by early July things seemed to have finally returned to normal. Then, with the arrival of new highly infectious variants like Delta, the tide changed.
A July 31 study found that protection against Covid had faded in proportion to the time elapsed since vaccination. According to the study’s authors, “people who were vaccinated in January 2021 had a 2.26-fold higher risk of advanced infection compared to people who were vaccinated in April 2021.” What this study told us is that vaccine-induced neutralizing antibody levels were significant, and when antibodies decrease, infections increase.
The flicker of hope was that, despite the increase in infections, vaccines would still work against variants to prevent serious disease. That hope faded a bit when the Israeli Ministry of Health found in August that nearly 60% of those hospitalized with Covid were vaccinated. Today just over 60% of the entire Israeli population is vaccinated.
It should be noted that it is natural that as a country’s vaccination level increases, a higher percentage of its Covid-19 infections occur in vaccinated people. What is still unknown are factors such as the severity of these advanced infections and the overall health of those infected.
Vaccination was even better than not getting vaccinated when it came to the likelihood of serious illness and death, but it was not quite enough to prevent hospitalizations. Israel has already begun deploying a third dose of Covid-19 vaccine. Early data show a dramatic improvement in defense: after 14 to 20 days, the risk of infection was reduced by 70-84%. What this Israeli follow-up study tells us, combined with the first, is that impellers are not just an option. A third required dose of the Covid-19 vaccine should be considered.
The need for three doses is becoming clearer. New data released by Moderna shows that a third dose of its vaccine significantly improves antibody levels for all variants, including 32-fold beta versions, 43.6-fold Gamma, and 42-fold Delta.
What is not so clear is where SARS-CoV-2 will take us from here. We know that the virus will change and that new variants will inevitably emerge regularly, and may be more infectious than those that have already taken root.
In addition to the three doses of current vaccines, we may need to prepare for the possibility of annual or semi-annual Covid vaccines in the coming years and the possibility of other means of protection: the wearing of masks, testing and quarantine and the development of prophylactic treatments and drugs, perhaps they should be used for many, many months. In the end, the main determinant of our ability to control Covid-19 is human behavior, not the behavior of the virus itself.
