Covid-19 Vaccines: Are Boosters Inevitable?
Covid-19 (SARS-CoV-2) vaccines are the great hope for a world made miserable by the pandemic. Vaccines will allow business, travel, and life to get back to normal. Children can go to school and playgrounds without fear, and you can hug friends and family.
But for how long? Will the protection be lifelong after the two doses most vaccines need, or will a booster be required? How likely is it that regular shots will be needed, like with the influenza vaccine?
Factors Determining Further Doses:
- Duration of immunity in normal persons
- Immunity achieved and its duration in special populations
- Covid-19 variants and their immune escape.
Duration of Immunity
Immunity isn’t always immortal. With time, antibody levels fall and vaccinated people become susceptible to the disease again. With the whooping cough vaccine, for example, immunity wanes and boosters are needed.
The Johnson and Johnson vaccine needs a single dose, as does the Sputnik Light vaccine. All the other Covid-19 vaccines need two doses, separated by varying intervals of three weeks to a few months. This primary vaccination by all vaccines given emergency use authorization (EUA) provides good protection to vaccinees.
Sputnik-V has been in use since September 2020; the other vaccines were approved from December 2020 onwards. We have only a few months of experience with the Covid-19 vaccines. We have evidence that two doses of mRNA vaccines generate antibody levels as high as after severe Covid-19. However, one study found these antibodies to reduce by 90% after 90 days. Several more studies are ongoing, and we await the results.
Thus, it is too early to know how long the immunity generated by any vaccine lasts. Most studies track the levels of antibodies and their fall over time to assess the duration of protection. However, we know that this is not the only measure of immunity. Cellular immunity plays a significant role, but is difficult to measure.
How do we Judge Immunity, Anyway?
After more than a year of the Covid-19 pandemic and half a year of using the vaccines, we do not know how to measure protection.
Almost all the vaccines work by generating antibodies to the spike protein of SARS-CoV-2 (Covid-19). The exceptions are the whole-cell vaccines, which probably induce antibodies against more than one antigen.
We measure antibodies, but we do not know what antibody levels protect against Covid-19 infection, severe disease, and death.
Besides, antibodies are not the only defense. Cellular immunity, based on T-cells, also contributes to protection. However, cellular immunity is more challenging to measure than antibody levels; it is usually done in research laboratories.
The real-world measure of vaccine efficacy is disease averted and lives saved. While we look into identifying laboratory measures of immunity, we assess vaccine efficacy by comparing vaccinated and unvaccinated people getting the disease.
Vaccine Efficacy in Special Populations
Certain people are at high risk of getting Covid-19 or of dying from it. People in residential care facilities, elderly citizens, health care workers, and others with occupational exposure are at particularly high risk. They may need a higher level of antibodies or other protective factors.
Another high-risk population is those with poor immune function:
- People with cancer
- People on chemotherapy
- Transplant recipients
- Other patients on other immunosuppressive therapy
- Persons with HIV and other immunosuppressive diseases.
These people may not develop adequate immunity after two doses of the vaccines. Additional doses (or boosters) may provide them better protection.
The Joint Committee on Vaccination and Immunization (JCVI, England) is drawing up plans to administer booster doses to fully vaccinated persons. The following people will be offered this booster in Stage 1:
- Immunosuppressed adults over age 16 years
- Residents of care homes for older adults
- All people over age 70 years
- Adults who are considered vulnerable
- Health, social, and other frontline workers.
Stage 2 will cover other persons considered to be at high risk.
Much of the vaccine efficacy data was generated in 2020, before many variants were in circulation. The efficacy data thus relates to the original Covid-19 (Wuhan) strain.
Today, the situation all over the world is very different. Variants appear in various countries and spread globally. In the UK, for example, the original Covid-19 strain was replaced by the Alpha strain in early 2021. In May 2021, 91% of cases in the UK were caused by the Delta strain.
Errors in the multiplication process by the virus produces variants. Some errors make the virus more transmissible, some enable it to cause more severe disease, and yet others allow it to escape neutralization by antibodies.
Variants also have some differences in structure, including the structure of the spike protein. When antibodies are unable to recognize this changed virus, protection is lost. This applies to antibodies acquired by getting and surviving Covid-19 disease, or by vaccination.
Variants and Vaccine Efficacy
Some of the variants have reduced susceptibility to vaccine-induced immunity. A UK study found that the Pfizer/BioNTech RNA vaccine and the AstraZeneca vaccines provided only 33% protection with one dose against the Delta variant, a significant reduction. Two doses of these vaccines provided better protection (60% with AstraZeneca; 88% with Pfizer/BioNTech). However, these numbers are less than those against the original strain of Covid-19.
The Beta variant also evades vaccine-generated immunity. A study of Novovax’s recombinant nanoparticle vaccine, NVX-CoV2373, found efficacy of only 51%, compared to over 90% against the original strain.
Health care systems worldwide have to continuously track the emergence and spread of variants and assess the protection of the vaccines against them.
As more variants appear, spread, and cause severe disease in previously vaccinated persons, we will need newer vaccines able to protect against such Covid-19 variants. In time, we may reach a situation similar to influenza: a new vaccine formulated and administered every year.
Decisions About Covid-19 Vaccines Boosters
These decisions are challenging at this time because we have insufficient knowledge about the currently used vaccines. In particular, we need data about:
- Effectiveness of vaccines beyond six months and one year
- Immunity and protection benefits of a third dose or booster in normal people and special populations
- Immunogenicity and reactogenicity of using the same versus different vaccines for the booster doses
- Susceptibility of Covid-19 variants to vaccine-induced immunity
- Most of all, the correlates of protection. How to assess whether an individual is protected against Covid-19
- The emergence and spread of Covid-19 variants
How Will We Know?
By watching vaccinated people to see how many get Covid-19, and how severe the disease is in these people.
Measuring antibodies in the laboratory is an easier way, but not definitive. It is entirely possible that people with low antibody levels are well-protected by cellular immunity. There is some evidence that the structural changes that protect the Covid-19 variants from antibodies do not protect from cellular immunity.
After a year or two years, we may see that many vaccinated people are getting Covid-19, but almost all have mild disease. Boosters would then be considered unnecessary.
On the other hand, if it is observed that a large proportion of vaccinated people are getting severe Covid-19, boosters would be advised.
Are Boosters Likely?
Reinfections and breakthroughs are both occurring, though not commonly.
Reinfections are a second episode of Covid-19 in people with a laboratory-documented earlier infection. With most diseases, natural infection generates effective, durable immunity. Reinfections seem to show that immunity against this virus does not last long, at least in some people.
Breakthroughs are the disease occurring in people that are fully vaccinated. It is difficult to say if the vaccine did not generate adequate immunity in these people, or if it waned quickly.
Covid-19 is a type of Coronavirus. Several other coronaviruses are in circulation and affect people repeatedly, causing cold, cough, and fever. We can expect Covid-19 to behave similarly.
Boosters are likely to be needed, but we can’t predict the frequency and type now. We haven’t enough data. Some answers should be available by the end of 2021, when the vaccines complete a year of use.
Which Vaccine for the Booster(s)?
Traditionally, we use the vaccine used for primary vaccination as booster doses, too. However, with Covid-19, vaccine science is evolving even as we have started using the vaccines.
By the time the need for a booster becomes apparent, we will also know which vaccines give the best protection. We already know that using different Covid-19 vaccines is safe for the recipients and generates a robust immune response.
Thus, the choice for booster vaccine will depend on:
- Proven efficacy and durability of protection
- Efficacy against variants in circulation
- Release of reformulated versions of vaccines covering circulating and emerging variants.
Vaccines are probably the best way to keep ourselves safe in the Covid-19 (SARS-CoV-2) pandemic. Governments around the world are vaccinating their people as quickly as possible. Certainly, people who take the vaccine are at lower risk for Covid-19, especially severe and fatal disease.
Vaccines are estimated to have prevented millions of infections and deaths already. Unfortunately, their protection may be reduced by waning immunity, the immune escape of virus variants, and other factors. Booster doses of the vaccines may be the way forward to keep ourselves safe and return the world to normalcy.
Borobia et al. Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial
Ibarrondo et al. Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses
JCVI interim advice: potential COVID-19 booster vaccine programme winter 2021 to 2022
Schramm et al. Poor humoral and T-cell response to two-dose SARS-CoV-2 messenger RNA vaccine BNT162b2 in cardiothoracic transplant recipients