Photo: Alena Shekhovtcova / Pexels
Recently, The Lancet An Indian task force of COVID-19 Commission issued a public statement saying that several cases of COVID-19 have been reported among people vaccinated across the country. The statement, shared by numerous newspapers, says: “The susceptibility to infections appears to be particularly high immediately after vaccination (either due to lower immunity or due to unsafe behavior), and an advertising campaign on the need to stay alert will help mitigate this risk.”
Some of my peers working in the larger COVID-19 hospitals in metropolitan cities have also observed something similar – that those who received vaccines and tested positive for COVID-19 within two weeks both outnumber those who have not been vaccinated and administer more severe course of the disease. However, the Indian Ministry of Health has not yet released such data.
Could these fears be true? And is the risk of increased frequency of infection or high severity of the disease associated with a particular vaccine? Let’s find out.
Original antigenic sin
There is an adequate immunological explanation that exists for this phenomenon. The speculation that vaccines could paradoxically increase the risk of infections may have originated after the 2009 influenza A (H1N1pdm09) pandemic, when four Canadian studies indicated that receiving the seasonal flu vaccine increased the risk of laboratory-confirmed infections. This led to five additional studies, each of which ensured these initial findings.
One proposed mechanism for this phenomenon is called original antigenic sin. It was first used to describe how one’s first exposure to the flu virus forms the result of subsequent exposures to antigen-related strains. (The antigen is the part of the object that elicits the immune response – like the spike protein of the new coronavirus.) This specific immune phenomenon explains the failure of the immune system to generate an immune response against related antigens.
When an individual is infected by a developed strain with a new dominant antigen, slightly different from the original strain against which the person was vaccinated, the immune system produces antibodies against the original strain. This occurs with high-affinity memory B cells that prevent activation of naive B cells, resulting in a weak immune response against the newer strain. So the risk of infection paradoxically increased in vaccinated individuals compared to unvaccinated individuals.
This phenomenon could work when different variants of the virus SARS-CoV-2 plays. As you may know, most existing COVID-19 vaccines are based on the wild-type strain that circulated around the world last year. However, by the end of 2020, many variants with mutations in the spike protein have emerged. These new variants have replaced their predecessors in most countries. Also in India it is feared that one or two key variants (B.1.1.7 and B.1.617) are circulating across the country.
So a vaccine can cause a strong immune response against the original epitopes contained in the ‘original’ strain due to preformed B cells. (“The antibody recognizes a particular part of the virus, called an epitope, and forms a link with it using a part called a paratope” – source.) These preformed compromised B cells outperform naive B cells and prevent them from mounting a strong response specific to the epitopes. contained in the new mutant.
As a result, the immune system becomes unable to mount a faster, stronger secondary response. The implication is that when the epitope varies slightly, then the immune system depends on the memories of the previous infection (with the wild-type variant) rather than mounting another primary or secondary response to the new epitopes present in the new variant (B.1.617 or B.1.1.7).
As a result, the immune response may be inappropriate against the new variant – because the immune system relies on memory instead of launching into a new response.
The Covishield vaccine is based on nucleic acid technology and works against a single SARS-CoV-2 antigen, the spike protein. Covaxin is based on the inactivated vaccine platform – where not only the stinging protein but other antigens are presented to the immune system to elicit an immune response. The chances of an inadequate response due to an original antigen are higher with the mere vaccines.
However, there are some other mechanisms, such as antibody enhancement (ADE), by which even inactivated vaccines such as Covaxin can improve the severity of disease.
During the development of COVID-19 vaccines, experts expressed concerns about the only approach for medium to long-term control of the pandemic. In one editorial in May 2020, Gregory Poland, of the Mayo Vaccine Research Group in New York City, raised similar questions. He wrote:
… issues of broad immunogenicity exist. Considering that this is an RNA virus, I believe it is important that more than one viral antigen be included in the vaccine. While the meaning remains hitherto unknown, researchers have already identified at least one mutation in the [receptor binding domain] of the spike gene. Additional mutations could lead to problems of original antigen sin with resulting disease improvement after exposure or to vaccines that simply have no effect in the future. Vaccines ‘S only’ are at risk for these problems, while vaccines, which include other relevant virus antigens SARS-CoV-2, considerably decrease this risk.
My colleague and I raised similar fears in a detailed review of the development and risks associated with the vaccines, published last year.
What should we do?
Some signals already show this unusual association at work. As discussed above, many clinicians and a reputed body of independent experts have raised the possibility of higher infection rates among vaccinated individuals. We should not dismiss this phenomenon as related only to “unsafe behavior”. Instead we should try to find out if our vaccines are effective.
Researchers should estimate the frequency and severity of disease among vaccinated and unvaccinated cohorts. we also separate the results based on individual vaccine use.
India is currently under the control of an unprecedented increase in COVID-19 cases. The things we do to protect ourselves must not unintentionally aggravate the disease. We must be prepared to wait for the unexpected – including focusing some of our efforts on developing multidrug vaccines.
Dr. Vipin Vashishtha, MD, FIAP, is a consultant pediatrician at the Mangla Hospital and Research Center, Bijnor.