BREAKING! Different Spike Proteins Of SARS-CoV-2 Variants And Whether By Infection or Vaccination Results In Diverse Immune Profiles

COVID-19 Immunity: Finally, the study findings of a new research by scientists from Imperial College London and Queen Mary University of London confirms what Thailand Medical News has been stating from day one. COVID-19 is not a homogenous disease rather every different SARS-CoV-2 variant or lineage and how the different SARS-CoV-2 spike proteins were introduced in the human host either by natural infection or via vaccine and how many times these spike proteins were introduced and in what combinations all will result in a diverse patterns of immune imprinting resulting in different human host immune profiles and also diverse patterns of pathogenesis and subsequent clinical conditions.

 
The impact of initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOC) is unknown.
 
The COVID-19 Immunity research team by studying a longitudinal healthcare worker cohort, found that after three antigen exposures (infection+two vaccine doses), S1 antibody, memory B cells and heterologous neutralization of B.1.351, P.1 and B.1.617.2 plateaued, while B.1.1.7 neutralization and spike T cell responses increased.
 
Serology using Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over 5-months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.
 
The study findings were published in the peer reviewed journal: Science https://www.science.org/doi/10.1126/science.abm0811
 
The new study shows that the first SARS-CoV-2 spike protein a person encounters, be it by vaccination or infection, shapes their subsequent immune response against current and future variants. That is, it imparts different properties that have an impact on the immune system's ability to protect against variants, and also affects the rate of decay of protection.
 
Already it is known that antibody levels wane over time following infection or vaccination, but the new study shows that an individual's protective immune responses are also affected by which strain or combination of strains they have been exposed to.
 
Almost 2 years into the pandemic, it is now being found that different individuals across the world have very different patterns of immunity to the SARS-CoV-2 virus, based on their exposure.
 
Around the world, individuals have been exposed to different SARS-CoV-2 variants and sub-variants such as the original Wuhan strain and/or Alpha, Beta, Gamma, Delta variants and now Omicron. In addition, people may be unvaccinated or have had one to three vaccine doses (which are programmed using the spike of the original strain).
 
Importantly it m ust be noted that every SARS-CoV-2 variant has different mutations in the spike protein, and the study team found that these shapes the subsequent antibody and T cell responses (the immune repertoire).
 
Dr Rosemary Boyton, a Professor from Imperial's Department of Infectious Disease told Thailand Medical News, "Our first encounter with spike antigen either through infection or vaccination shapes our subsequent pattern of immunity through immune imprinting. Exposure to different spike proteins can result in reduced or enhanced responses to variants further down the line. This has important implications for future proofing vaccine design and dosing strategies."
 
The study team looked at "immune imprinting"' in healthcare workers after two doses of Pfizer vaccine to understand their immune response to infection by variants of concern. It involved a detailed, longitudinal follow-up of the Barts COVIDsortium healthcare worker cohort of 731 individuals, who have been followed since March 2020.
 
The study team compared protective immunity between people infected in the first wave with the original strain, or in the second wave with the Alpha variant.
 
Interestingly in second wave infected people, three encounters with different spike proteins (i.e., with sequences following Alpha infection and two vaccine doses) resulted in lower protective (neutralizing) antibody responses against the original strain and the Beta variant, yet higher responses against Delta when compared to encounters with three of the same spike sequences (i.e., all with the original, first-wave sequence through infection and two vaccine doses).
 
The research also showed that neutralizing antibody responses against variants decay differentially over time after these mixed spike encounters.
 
It was noted that there were a number of cases of Delta breakthrough infection in two dose vaccinated individuals in the study.
 
Levels of spike antibodies measured three weeks after the second vaccine dose were high, yet the actual levels of protective neutralizing antibody responses against Delta had fallen to zero five months after their second dose.
 
Importantly however, a third dose of the original spike from a booster vaccine uplifts the antibody response.
 
Dr Boyton added, "These study findings highlight the importance of third dose booster vaccination to reduce viral transmission.”
 
The study team stresses that despite breakthrough infections being seen, immune responses to vaccination are still effective in preventing severe disease and death from COVID-19 in the face of Alpha, Beta, Gamma and Delta variants.
 
From the study findings, the research team says that vaccine design and dosing strategies need to be future proofed to take maximum advantage of immune imprinting.
 
Importantly this will involve enhancing the breadth of protection rather than tweaking the vaccines with the latest variant spike sequences.
 
Dr Danny Altmann, a Professor from Imperial's Department of Immunology and Inflammation further added, "We've recently had some very large studies making the point that vaccine immunity wanes quite rapidly. This leaves us vulnerable to Delta breakthroughs, and protection can generally be rescued by a third dose. This study now offers considerable new detail about who is susceptible and when. You can be someone who made a great response to the vaccine and still fall prey to Delta breakthrough if you haven't had a booster."

He further added, "The really surprising news was finding that people infected with the Alpha variant had such different patterns and waning of immunity to other variants. Immune imprinting means we're now all walking around programmed slightly differently for our future protection.The challenge is how to broaden the population's immunity in the right way as we need to ensure the widest coverage possible. Currently, with the Omicron variant emerging, it's vital that people get their booster vaccines. But in the future, we should consider how we can create vaccines that broaden our immune response even more to protect against other new variants of concern."
 
Dr Áine McKnight, a Professor from Queen Mary University of London warned, "Modeling the future course of the pandemic is becoming increasingly complicated."
 
"Our study highlights the importance of understanding the immune responses to the different SARS-CoV-2 variants in the context of existing vaccines, in order to make informed decisions about future vaccine design, strategy and timescales," said Dr Catherine Reynolds, co-researcher from Imperial College London.
 
Professor Dr Joseph Gibbons, from Queen Mary University of London said, "The emergence of new variants with the potential to evade immunity has shown that we must future-proof the next-generation of vaccines. We studied immunity over time in people infected with different variants and found that vaccine responses are highly variable depending on the infecting strain. These findings can be used to ensure vaccine design is optimal. This work highlights the importance of continually monitoring the effectiveness of vaccines against new variants such as Omicron."
 
The COVIDsortium is a collaborative partnership between researchers at Imperial College London, Queen Mary University of London, Bart's and the London School of Medicine and Dentistry, University College London, Barts NHS Trust, Royal Free London NHS Trust and UK Health Security Agency, Porton Down.
 
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