CME INDIA Presentation by Admin.

“Do not miss it, have it to Enjoy” – Editor CME INDIA

Immunological memory is a mechanism to protect us against reinfection. For all vaccine success, antibodies produced by B cells are most vital defense mechanism. Just like infection, vaccination is key to achieving protective immunity. Now when we are in the early part of vaccination, lots of quarries are in our minds.

Many physicians feel that vaccines have been developed with hurried pace and no proper safety data exists. Any untoward incident, if occurs, makes us suspicious. Although, such incidents are most probably unrelated to vaccines, it drives public to panic mode. I myself got vaccinated on 01/02/2021 (Editor).

CME INDIA Discussion

Dr Awadhesh K Singh DM Endo., Kolkata:

What is the % rate of protection after the first dose of AZ vaccine?

Dr N K Singh:

• For the Oxford-AstraZeneca vaccine, things are a bit different. As per paper published the vaccine offers protection of 64.1% after at least one standard dose. This compares to 70.4% if you’ve had two full doses, or – oddly – 90% in people who have had one half dose followed by one full dose.
• Meanwhile, based on these unpublished data the Vaccine Committee has estimated that, from three weeks until 9-12 weeks after the first injection, the vaccine prevents around 70% of cases of serious disease.

Dr Awadhesh K Singh, DM, Endo., Kolkata:

Some fewer known facts about Covishield you took:

1. Even one dose of AZ-Oxford aka Covishield has shown to produce neutralising antibody in 91-100% of healthy adults on day 28 – published in Lancet on Aug 15, 2020.

2. Covishield was innovated to be a single dose vaccine initially COV001UK but finally tested after 2 doses in SBRCT – COV 001UK/002UK/003Brazil/005South Africa. In fact, SA arm has 3 dose schedule – being studied!

3. Even in phase 3 trial Covishield offered 64% (95%CI 51-74%) protection overall 21 days after first dose.

4. The protection at day 21 of first dose was as high as 71% in Brazilian cohort (54-82%) to as low as 55% UK cohort (30-71%).

5. The single dose of J&J vaccine is based on the same concept of viral vector innovated by AZ-Oxford vaccine.

Morale: Don’t miss even a single dose of Covishield when offered. 2nd dose will only boost the response further produced by the first dose!

Dr Arvinda J, Bengaluru and Dr Prabhat Agarwal, Agra:

Is 2nd Dose of vaccination best after 28 days or 3 months?

Dr Shashank Joshi, DM Endo, Mumbai:

The big question is wait for 90 days or do the 28 days; UK deferred for better Immunogenicity.

Dr Awadhesh Kr Singh:

UK messed it – because they used it on the basis of Pfizer and Moderna data as Heavily criticised in BMJ. In Phase 1/2 AZ-Oxford vaccine maximum neutralising antibody was observed at day 28, although in phase 3 trial they went from 4-12 weeks… suggests only an additional 6-7% improvement in efficacy after the 2nd dose.

CME INDIA Learning Points

Take Vaccine, make a stronger foot print

• Change your status with vaccination, challenge your immune system, let it be triggered.
• This can leave a footprint which will keep you protected.

How long memory confers immunity

• After the 1st dose of vaccine first (or primary) response, immune system ‘‘learns’’ how to neutralize the invading organism.
• This knowledge is retained as immunological memory.
• It provides ongoing protection from the pathogen.
• This immunity can exist as a shield. It will block infection at the outset, can be reactive, can trigger rapid action by re-exposure to a pathogen that has avoided or overwhelmed the shield.
• It is worth to remember that protective components of the immune memory can diminish to a point of non-functionality in course of time.

The unique Immune system

• Lymphocytes are the key cells of the immune system.
• Infection triggers a lymphocyte response, it induces a small number of pre-existing B and T cells to proliferate, creating a small army of cells specific for, and thus able to combat, the infectious agent.
• B and T cells are triggered to respond by recognizing a part of the pathogen through their antigen receptors with a certain strength.
• Each B cell and T cell expresses on their surface an antigen receptor.
• It is different to all others such that all possible invaders have their own, pre-existing, matching B and T cells ready to respond if and when required.
• Some pathogen-specific B cells are induced to differentiate and secrete their antigen receptors into the blood in form of antibodies (Abs).
• Antibodies circulate through the body, binding to the pathogen that triggered the response wherever it occurs.
• When the pathogen has been subdued and the response is effectively over most pathogen-specific B and T cells die.
• But a small number of these recent combatants—B cells, T cells, and Antibodies secreting plasma cells (PCs)—persist as specialized, long-lived immune memory cells.

Hope for ‘‘best of the best’’

• Our immune system uses ‘‘best of the best’’ to protect from re-infection by SARS-CoV 2.
• We develop pathogen-specific Antibodies which would act as a shield against reinfection.
• If the number of antibodies in circulation drops, or if the pathogen varies from the initial infection, the shield may not be protective.
• Then a re-run of the response would be required.
• Getting a memory of the initial pathogen is a crucial part of immunity.
• Immune memory should have both specificity and the capacity to adapt to potential diversification of its targets.

What happens in your body after Vaccination?

• We develop ability to secrete high-affinity antibodies.
• Just after infection or vaccination, activated pathogen-specific CD4+ T cells and B cells interact.
• The T cells direct the B cells to proliferate, to switch the class of their antigen receptor (surface-bound Ab), to establish a germinal centre.
• A fraction of these B cells differentiates into the initial form of Ab-secreting cells called plasma blasts.
• Plasmoblasts appear within days of the infection and secrete antibodies into the blood—and thus throughout the body.
• The B cells promote the differentiation of the T cells into specialized T follicular helper (Tfh) cells that there after direct the behavior of the B cells in the immune response.
• Memory shaped by infection and vaccination.

Burning Questions

• Does infection or vaccination lead to the production of immune memory that will neutralize future infection?
• How long does protection last?
• Is it capable of recognizing variants of SARSCoV-2?

The ray of Hope

• At present, we lack the systematic population studies required to determine the full extent of protection provided by previous infection or vaccination.
• Confirmed reports of re-infection are very rare.
• Antibodies induced by either infection or vaccine candidates do develop neutralizing specificities.
• There is every reason to be optimistic of immunity to SARS-CoV-2 developing from infection and from vaccination.
• The Memory B Cells has been found in recovered patients up to 6 months post infection.
• “Another encouraging aspect is that coronaviruses ‘‘proofread’’ their relatively large genome to maintain integrity, thereby limiting diversification, which is in contrast to most other RNA viruses that continuously evolve by mutating their genome.” (1)

Story is Happy Ending

• A hallmark of immune responses to pathogens is to create a memory of the response, which is the persistence of small numbers of pathogen-specific B and T cells and the Plasma cells.
• These secrete pathogen-specific Antibodies.
• Immune memory may block future infections without symptoms developing either by continued production of neutralizing Antibodies from long-lived Plasma cells.
• In due course if antibodies amount diminishes, recalling of memory B and T cells happens which rapidly produce new Plasma cells and restoring of high-affinity, neutralizing Antibodies in circulation occurs.
• Protection from infection is generated through vaccination in the same way.
• Counteracting any ongoing variability of the pathogen is possible by specific vaccine. Although we do not know much about it.
• Believe it. The immune system has evolved to address these issues.
• The prospects of widespread immunity to SARS-CoV-2, by vaccination, appear to be very strong.

CME INDIA Tail Piece

Single-Shot Janssen COVID-19 Vaccine is coming

• It Met Primary Endpoints in Interim Analysis of its Phase 3 ENSEMBLE Trial.
• Vaccine Candidate 72% Effective in the US and 66% Effective Overall at Preventing Moderate to Severe COVID-19, 28 Days after Vaccination.
• 85% Effective Overall in Preventing Severe Disease and Demonstrated Complete Protection Against COVID-19 related Hospitalization and Death as of Day 28.
• The Janssen COVID-19 vaccine candidate demonstrated complete protection against COVID-related hospitalization and death, 28 days post-vaccination.
• There was a clear effect of the vaccine on COVID-19 cases requiring medical intervention (hospitalization, ICU admission, mechanical ventilation, extracorporeal membrane oxygenation (ECMO), with no reported cases among participants who had received the Janssen COVID-19 vaccine, 28 days post-vaccination.
• “These Topline results with a single-shot COVID-19 vaccine candidate represent a promising moment. The potential to significantly reduce the burden of severe disease, by providing an effective and well-tolerated vaccine with just one immunization, is a critical component of the global public health response,” – Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer, Johnson & Johnson.
• A one-shot vaccine is considered by the World Health Organization to be the best option in pandemic settings, enhancing access, distribution and compliance.
• Single-shot compatible with standard vaccine distribution channels provides important tool in pandemic setting.

Source:

1. Quast and Tarlinton, B cell memory: understanding COVID-19, Immunity (2021), https://doi.org/10.1016/ j.immuni.2021.01.014(Story is based on this article)
2. https://www.jnj.com/johnson-johnson-announces-single-shot-janssen-covid-19-vaccine-candidate-met-primary-endpoints-in-interim-analysis-of-its-phase-3-ensemble-trial

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