Is ‘original antigenic sin’ complicating indian vaccination drive against Covid-19?

Abstract

India is in the grip of a devastating second wave of Covid-19. Many experts believe new variants of concern (VOC) are behind this unprecedented surge. Some media reports are hinting toward higher risk of Covid infection following Covid vaccinations. ‘Original antigenic sin,’ in which a prior exposure to an antigen leads to an ineffective response to a related antigen, may offer one immunological explanation for this unusual association. There is an urgent need of undertaking a detailed study to prove/disprove this association.

KEYWORDS:

• Covid-19
• original antigenic sin
• vaccines

India is in the grip of a devastating second wave of Covid-19. Many experts believe new variants of concern are behind this unprecedented surge.

Recently, ‘Lancet Covid-19 Commission India Task Force’ made a public statement that several cases of infections have been reported after taking Covid vaccinations across the country.¹ The statement states, ’The susceptibility to infections appears to be particularly high immediately after vaccination (either due to lower immunity or due to unsafe behaviour), and an advocacy campaign on the need to remain vigilant will help mitigate this risk.’ Some other reports in media have also pointed toward this unexpected association and ‘reduction in immunity’ following vaccination.

The speculation of vaccines paradoxically increasing the risk of infections possibly originated first following the 2009 influenza A (H1N1pdm09) pandemic when four Canadian studies suggested that receipt of seasonal influenza vaccine increased the risk of laboratory-confirmed 2009 pandemic influenza A virus infection.² One proposed mechanism behind this phenomenon is ‘original antigenic sin’ (OAS) which was first used to describe how first exposure to the influenza virus shapes the outcome of subsequent exposures to antigenically related strains.³ When an individual is infected by an ‘evolved’ strain slightly different from the ‘original’ strain against which the person has been vaccinated, the immune system produces antibodies against the ‘original’ strain through preformed high-affinity memory B cells that inhibit activation of naïve B cells resulting in a weak immune response against the new ‘dominant’ strain. Hence, the risk of infection by a new strain paradoxically increased in vaccinated individuals as compared to unvaccinated individuals.

The mutation in the SARS-CoV-2 virus may have led to this phenomenon. Most of the current Covid vaccines are based on the wild strain D614G which was the dominant strain at that time. However, during the end of 2020, many variants with mutations in the ‘spike’ protein of the virus have emerged. In India, a few key variants (UK B117, Indian B1617 and its three sub-lineages) are believed to be circulating all over the country and may have replaced their predecessor, D614G.⁴ Thus, the vaccine has the capability of mounting a robust immune response against the original epitopes contained in the D614G virus due to pre-formed committed B-cells. These B-cells outnumber the naïve B cells and prevent them to elicit a strong antibody response, specific to the epitopes contained in the new variant. This results in an inadequate immune response since the immune system fails to adapt and instead relies on its earlier memory to mount a response.

‘Covishield,’ produced by M/s Serum Institute of India (under license from AstraZeneca), and ‘Covaxin,’ developed by M/s Bharat Biotech in association with the Indian Council of Medical Research, are the two vaccines being employed by the Indian government for mass vaccination against Covid-19 disease in India. The ‘Covishield’ is a viral vector vaccine having Chimpanzee’s Adenovirus as a vector in which genes encoding for ‘spike’ protein of the SARS-CoV-2 virus are inserted. On the other hand, the Covaxin is developed on the inactivated vaccine platform in which not only ‘spike’ protein, but other antigens are also presented to the immune system to elicit an immune response. The chances of inadequate response due to OAS are higher with the ‘Spike only’ vaccines. During the development of the Covid vaccines, some experts have raised concern over ‘Spike only’ vaccine approaches and feared OAS may affect vaccine-induced protection against emerging variants.⁵ Some have also argued the need of incorporating epitopes from other SARS-CoV-2 antigens like nucleocapsid protein for extra benefits.⁶

The Lancet India Covid-19 Task Force report¹ does not mention whether vaccinated individuals had only SARS-CoV-2 infections or full-blown symptomatic disease. Furthermore, no such information is also provided by the government health agencies. Based on available data, it is difficult to comment whether breakthrough infections observed after primary vaccination and presumed OAS resulted in full-blown disease or whether such infections are attenuated and generally not serious. We should not dismiss this phenomenon only related to the ‘unsafe behaviour’ of vaccinated individuals. There is an urgent need for a detailed study on the frequency and severity of the SARS-CoV-2 infections and the disease among the vaccinated and unvaccinated cohorts. We should also segregate the findings based on individual vaccine use.

Disclosure of potential conflicts of interest

I hereby declare that there exist no commercial or financial relationships that could, in any way, lead to a potential conflict of interest.