CME INDIA Presentation by Admin.

Two paper published on February 25, 2021 in Lancet recommends antibody testing before 2nd dose to decide whether you need it or not.

How Vaccination programmes can maximise early impact

  • We know that Rapid vaccine-induced population immunity is a key global strategy to control COVID-19.
  • So, Vaccination programmes must maximise early impact.
  • This becomes extremely important with accelerated spread of new variants.
  • Most vaccine platforms use a two-dose prime-boost approach to generate an immune response against the virus S1 spike protein.
  • The titres of Virus spike protein correlate with functional virus neutralisation and increase with boosting.

What is the message of article Published Online February 25, 2021 in The Lancet?

( S0140-6736(21)00502-X)

  • Immunological responses to single-dose BNT162b2 using a combination of serology, live virus neutralisation, and T-cell enzyme linked immunospot (ELISpot) assays was investigated.
  • 72 HCWs in UK who were vaccinated between Dec 23 and Dec 31, 2020.
  • They provided blood samples at the time of receiving their first dose of BNT162b2 vaccine and 21-25 days after vaccination.
  • As BNT162b2 mRNA encodes the spike glycoprotein of SARS-CoV-2, investigators assessed immune responses to spike protein post-vaccination.
  • Anti-S titres were significantly higher in individuals with previous natural infection than in infection-naive individuals. Anti-S titre is reported to correlate with in-vitro virus neutralisation.
  • Interestingly investigators also assessed post-vaccination T-cell responses using the T-SPOT Discovery SARS-CoV-2 (Oxford Immunotec, Oxford, UK), which includes a panel of five SARS-CoV-2 peptide pools.
  •  Post-vaccination, participants with evidence of previous SARS-CoV-2 infection at baseline mounted very strong T-cell responses to spike peptides.
  • In the infection-naive group, post-vaccination T-cell responses to spike peptides were significantly weaker than in individuals with previous infection.
  • Message is loud and clear that individuals with previous SARS-CoV-2 infection generate strong humoral and cellular responses to one dose of BNT162b2 vaccine, with evidence of high titres of in-vitro live virus neutralisation.
  •  Most individuals who are infection-naive generate both weak T-cell responses and low titres of neutralising antibodies.
  • Thus, the serological evidence of previous disease at baseline mount robust antibody and T-cell responses after a single dose of vaccine is paving an exciting path to formulate public health policy.
  • Equally important is to understand that infection-naive individuals mount very little demonstrable response to single-dose vaccination. It might not provide sufficient immunity to protect from clinical disease or viral shedding.
  • These persons need second vaccine without fail.

Serological response inversely correlates with age

  • In keeping with published reports of other vaccines, serological response to BNT162b2 inversely correlates with age.
  • A good % do not develop antibody after first dose especially with increasing age.
  • Dr A K Singh comments: Don’t be upset if you haven’t developed antibodies after first dose – take it at 28 days! Other may delay especially with AZ vaccine.

Second Dose Dilemma
Table: Pfizer data

Previous infection could be analogous to immune priming.

  • The concept of the first prime vaccine dose acting as boost is well understood so a second dose might not be needed.
  • One recent UK study did a nested case-control analysis of 51 participants of COVIDsortium.
  •  These underwent weekly PCR and quantitative serology testing from the day of the first UK lockdown on March 23, 2020, and for 16 weeks onwards.

Second dose dilemma
Courtesy, The Lancet: Published online February 25, 2021 Manisty, Ashley D Otter, Thomas A Treibelet al)

  • Study concluded that among previously uninfected, seronegative individuals, anti-S titres after one vaccine dose were comparable to peak anti-S titres in individuals with a previous natural infection who had not yet been vaccinated.
  • Among those with a previous SARS-CoV-2 infection, vaccination increased anti-S titres more than 140-fold from peak prevaccine levels.
  • These findings point to avoid reactogenicity after unnecessary boost risks.
  • Such reactogenicity could be avoidable and can stop unwelcome increase in vaccine hesitancy.
  • These findings do provide a rationale for serology-based vaccine dosing to maximise coverage and impact.

T Cell are happy but how you Know

  • Oxford Immunotec Updates Their T-SPOT® Discovery SARS-CoV-2 Kit and Include a New Panel to Detect T Cells Reactive to Endemic Coronaviruses
  • These kits have been used successfully in the UK study which has been quote above.
  • This additional panel containing epitopes of high genetic homology to endemic human coronaviruses (HCoV) facilitate research into the role HCoV play in the immune response to SARS-CoV-2 infection.

(Differential T cell reactivity to seasonal coronaviruses and SARS-CoV-2 in community and health care workers. medRxiv. Published online January 15, 2021:


By Dr A K Singh Endo, Kolkata

  • UK and EMA has approved AZ-Oxford vaccine at 3-month (12-weeks) interval because of best efficacy when compared to 4, 6 and 8-weeks.
  • However, we are increasingly learning that ideally these intervals should be based on antibody response following first vaccination and therefore ideal time interval can be questionable at the moment.
  • Those who didn’t produce enough antibody may be best fit at 4-weeks while others may delay up to 12-weeks depending on falling antibodies.
  • We are in the mid of an undergoing trial in India. Preliminary data suggest nearly 20% is not developing satisfactory antibody though between 21-28th day of first dose.
  • And, clearly those who had Covid in past must delay their 2nd dose as far as practicable. Those who had Covid are having exceptionally high antibodies after first dose. I have looked in to data of nearly 100 past Covid participants out of 350 odd participants (all doctors) and 100% have exaggerated response perhaps not requiring 2nd dose at 28-day interval. Two paper published in Lancet yesterday recommended delaying 2nd dose in post Covid people.

CME INDIA Tail Piece

  • SIREN study of vaccination in health care workers. A single dose of Pfizer vaccine effective at preventing infection by 70% after 21 days. Second dose increased efficacy to 86%!
  • Conclusion: SIREN study demonstrates that the BNT162b2 vaccine effectively prevents both symptomatic and asymptomatic infection in working age adults; this cohort was vaccinated when the (
  • Dr Uman Dhruv, Ahmedabad: Thanks for sharing. The finding that it has prevented asymptomatic infection is extremely crucial.
  • This means a physician in covid ward doesn’t have to isolate from family members after two weeks after two doses. Compare that against last year when we used to change clothes so many times just so we can eat with our family on the same table!
  • The US Food and Drug Administration (FDA) granted emergency use authorization (EUA) to the Ad26.COV2.S vaccine from Janssen/Johnson & Johnson (J&J) for people 18 and older after reviewing its safety and efficacy data.
  • J&J vaccine offers one-dose convenience and storage at conventional refrigeration temperatures.
  • We have yet a third vaccine that is highly effective at preventing COVID, and even more effective at preventing severe COVID
  • This vaccine has also been shown to be effective against the B.1.351 strain that was first described in South Africa
  • One recent concern centers on people aged 60 years and older. Documents the FDA released earlier this week suggest a lower efficacy, 42%, for the J&J immunization among people in this age group with certain relevant comorbidities. In contrast, without underlying conditions like heart disease or diabetes, efficacy in this cohort was 72%.

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