Increased COVID infections in vaccinated caused by Original Antigenic Sin?

The latest Public Health England reports are showing that in some age groups the rates of COVID infection are higher in vaccinated patients than unvaccinated. The report states, "In individuals aged 40 to 79, the rate of a positive COVID-19 test is higher in vaccinated individuals compared to unvaccinated."

The results of this report has been highlighted recently by the ITV News reporter, Robert Peston who despite being double-vaccinated became ill with COVID. He wanted to know how common his experience was, and he was shocked by what he found. He says, “I am surprised these statistics have received so little attention and have occasioned so little debate.”

Reasons why COVID vaccines may not work

There are a number of reasons as to why mRNA vaccination could potentially cause an increased risk of COVID infection, some of the main causes include:

1. The well reported drop in white cell count (neutrophyls) immediately following vaccination.

2. Immune focus on a single antigen (spike protein) and associated variant selection.

3. Antibody dependent enhancement; anti-SARS-CoV-2 antibodies could actually exacerbate COVID-19 through antibody-dependent enhancement (ADE). ADE is a reminder that not all antibody responses are helpful and some can be harmful.

4. According to the Journal of Immunology Original Antigenic Sin, or OAS.

Original antigenic sinWhat is original antigenic sin?

The body's immune system can normally recognise foreign infectious material from the types of structures displayed. These structures that can cause an immune response - such as the production of antibodies are known as antigens.

The virus 'variants' vary because they have slightly different or modified antigenic structures around their surfaces. Evolution will normally select for those viruses with antigenic structures that evade or are not recognised by the immune system.

The first (original) exposure of the immune system to an antigen (or the 'pioneer' strain) is critical for how immunity will subsequently develop, and the composition of the antibody repertoire (i.e. the quality of your defence mechanisms). The more surface antigens that the immune system responds to, the more 'memory' the immune system will have for dealing with subsequent infections. 

Natural immunity v. mRNA vaccines

This biological phenomenon could be problematic for a vaccine with only a single (spike protein) antigen.

If memory B cells (the cells responsible for producing antibodies) respond to an infection with a related, but antigenically distant pathogen, the memory response can not only be ineffective but possibly diminish the effectiveness of naive B cells capable of producing neutralising antibodies. It is understood that this potential downside of immune memory must be considered when attempting to design vaccines incase a vaccine formulation induces an immunological setback that prevents protective immunity to a new strain of virus.

So, if OAS plays such an important function in preventing subsequent infections, the nature of the first (original) antigenic stimulus (or vaccine) is potentially a fundamental factor for preventing subsequent infections. the vaccine may produce an initial immune response, but OAS then suppresses subsequent responses to variants.

The 2019 Journal of Immunology paper concludes stating:

Recently, there has been a major expansion in research and funding dedicated to the development of better and more broadly protective influenza virus vaccines. This, in turn, has catalyzed substantial renewed interest in defining the mechanisms governing OAS and the influence that pre-existing immunity exerts on subsequent vaccine responses. Although many specific instances wherein OAS-like responses have been observed, both experimentally and during natural influenza virus epidemics, have been studied in great detail, a holistic and predictive model of the situations in which OAS responses occur is far from being realized. To accomplish this goal, considerable effort will need to be directed to understanding the complex interactions between Abs, cell types, and Ags that ultimately determine response outcomes.

Special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. Full medical glossary
One of a group of special proteins in the blood that are produced in response to a specific antigen and play a key role in immunity and allergy. Full medical glossary
A substance that prompts the immune system to fight infection with antibodies. Full medical glossary
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A sudden outbreak of infection that affects a large proportion of a population. Full medical glossary
A viral infection affecting the respiratory system. Full medical glossary
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The organs specialised to fight infection. Full medical glossary
Relating to the structure and function of the immune system, the organs in the body that are specialised to fight infection. Full medical glossary
Invasion by organisms that may be harmful, for example bacteria or parasites. Full medical glossary
A viral infection affecting the respiratory system. Full medical glossary
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The means of producing immunity by stimulating the formation of antibodies. Full medical glossary
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