A BRIEF TOUR OF VACCINES AGAINST COVID 19 - CSQP FCCM D(ABMM) RAYMOND TELLIER MD MSC FRCPC ASSOCIATE PROFESSOR MCGILL UNIVERSITY - OHCOW
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A brief tour of vaccines against
Covid 19
Raymond Tellier MD MSc FRCPC
CSQP FCCM D(ABMM)
Associate Professor McGill University
Coronaviridae Torovirinae Coronavirinae Alphacoronavirus Betacoronavirus Gammacoronavirus Deltacoronavirus
Human Coronaviruses • Long-established Coronaviruses causing the common cold: - OC43 -HKU1 -NL63 -229E • Emerging Coronaviruses SARS-CoV (SARS-COV-1) MERS-CoV SARS-CoV-2 ( causal agent of COVID-19)
Cui J et al Nature Reviews Microbiology 2019; 17: 181-192
MERS-CoV, CDC accessed Nov 4 2013
SARS-CoV-1, Courtesy Dr M Petric BCCDC
SARS-CoV-2 NIAID Feb 17 2020
Cui J et al Nature Reviews Microbiology 2019; 17: 181-192
Massive vaccine development • As of January 2021: > 172 vaccines at various stages of development; 63 in Human clinical trials ( Kyriakidis et al npj Vaccines 2021 (28)) • Technologies involved included mRNA vaccines, vector based vaccines, DNA vaccines, inactivated viruses vaccines, live attenuated vaccines, cloned proteins /vlp
Vaccines authorized in Canada • Pfizer/BioNTech (BNT162b); mRNA vaccine • Moderna/ US NIAID (mRNA-1723): mRNA vaccine • Aztra Zeneca/Oxford University/ Covishield (AZD1222: adenovirus vector • Johnson& Johnson/Janssen (Ad26COV2.S): adenovirus vector
mRNA vaccines efficacy
Clinical trials
• Pfizer: 95% efficacy in preventing illness
(Polack FP et al NEJM 2020; 383: 2603-2615)
• Moderna: 94.1% efficacy in preventing illness
(Baden LR et al NEJM 2021; 384: 403-416)mRNA vaccines in the field (1) • Adjusted vaccine effectiveness against infection (RT- PCR) of BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) combined was 91% (95% CI 76%-97%) after full vaccination and 81% (95% CI 64%-90%) after one dose. • Compared to infections in unvaccinated persons, persons with breakthrough infections had 40.2% (95% CI 16.3%-57.3%) lower viral RNA load,reduced illness severity, including fewer days with symptoms (mean days 10.3 vs. 16.7). • (Thompson MG et al NEJM DOI: 10.1056/NEJMoa2107058)
(from day of 1st dose)
Side effects Chambers C “Comparing vaccines: efficacy, safety and side effects https://healthydebate.ca/2021/03/topic/comparing-vaccines/
Anaphylactic reactions to mRNA
vaccines
• Anaphylaxis is a life-threatening allergic reaction
that can occur after vaccination, with onset typically
within minutes to hours.
• The initial estimated reporting rates for anaphylaxis
in the US were 11.1 cases per million doses
administered of the Pfizer-BioNTech vaccine
(December 14-23, 2020) and 2.5 cases per million
doses administered of the Moderna vaccine
(December 21, 2020-January 10, 2021) (Shimabukuro TT et
al Jama 2021; 325(11): 1101-1102)
• Influenza vaccine 1.35 per million; Tdap: 0.53 per
million (Risma KA J Allergy Clin immunol 2021; Jun 147(6): 2075 2082)Myocarditis and Pfizer vaccine • As of June 23, approx. 1000 cases of myocarditis following Pfizer vaccination have been reported, out of 177 million recipients of the vaccine • Mostly among adolescents and young adults; more often several days after 2nd dose • Link with vaccine unclear • All recovered without sequelae • Myocarditis can be seen in patients suffering from Covid illness; some say up to 7% of Covid deaths involve myocarditis (Siripanthong B et al Heart Rytm 2020; 17(9) 1463-1471)
Astra Zeneca vaccine efficacy
Clinical trials
• 67% efficacy in protecting against infection
after 1 dose; 70% 14 d after 2 doses
• 100% protection against severe disease
• (Creech CB et al JAMA 325; 13: 1318-1320,
2021)AstraZeneca efficacy in the field • In the UK a single dose of either the Pfizer or the AstraZeneca offered equal 80% protection against severe disease • Pfizer and AstraZeneca “offer similar levels of protection in adults aged 70 and older” • ( Lopez Bernal J et al BMJ 2021;373:n1088 | doi: 10.1136/bmj.n1088
Side effects Chambers C “Comparing vaccines: efficacy, safety and side effects https://healthydebate.ca/2021/03/topic/comparing-vaccines/
AstraZeneca Severe allergic reactions/anaphylaxis • 41 cases of severe allergic reactions in 5 millions vaccinees in the UK (European Medicine Agency March 2021) • 23 anaphylaxis cases per million doses (Medicines & Healthcare products Regulatory Agency, UK)
Astra Zeneca
Rare but severe and unusual blood
clots
• Rare instances of unusual blood clots with low
levels of platelets ( thrombocytopenic
thrombosis); apparently immune mediated
platelet aggregates, similar to heparin induced
thrombosis
• Also seen with Johnson & Johnson vaccine
• In Canada incidence about 1:250 000 doses
• Presentation can be severe and life threatening
(eg cerebral venous thrombosis)Heterologous Prime and Boost • 1st dose with AstraZeneca, second with Pfizer • UK study: safe but higher incidence of mild bto moderate side effects; immunological data pending • Spain study safe, and second dose provided significant increase of immune response against SARS-CoV-2
Sars-CoV-2 variants of concerns • Alpha (B.1.117) initially identified in the UK • Beta ( B.1.351) initially identified in S. Africa • Gamma ( P1) initially identified in Brazil • Delta ( B.1.617.2) initially identified in India
Peck KM, Lauring A J Virol 2018 92; 14: e1031-17
SARS-CoV2: rate of mutation • 50% of the rate of Influenza A virus • 25% of the rate of HIV
Variant B1.1.7 (UK) https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563
An illustration of the variant found in the United Kingdom. To infect a cell, the virus's spike protein (red) has to bind to a receptor on the cell's surface (blue). Mutations help the virus bind more tightly. Science Source https://www.sciencesource.com/
Wikipedia
Variant B1.1.7 and mortality (1) • Initial evaluation: no differences • Further evaluation : increased incidence of severe illness but several limitations in the studies • Based on these analyses, there is a realistic possibility that infection with VOC B.1.1.7 is associated with an increased risk of death compared to infection with non-VOC viruses. (NERVTAG 21/1/21)
Variant B1.1.7 and mortality (2) • “Based on these analyses, it is likely that infection with VOC B.1.1.7 is associated with an increased risk of hospitalisation and death compared to infection with non-VOC viruses.” (NERVTAG 21/2/11) • “It should be noted that the absolute risk of death per infection remains low.” (NERVTAG 21/2/11)
Variant B.1.351 ( variant Sud-Africain)
Sabino EC et al Lancet Feb 6, 2021; 397: 452-454
Wall EC et al The Lancet June 28, 2021
Abu-Radad LJ et al doi:10.1056/NEJMc2104974
Delta Variant
(B.1.617.2)
• Initially identified in India
• Approx. 15 mutations in the Spike alone
compared to reference strain, including L452R
and P681R
• Increased transmissibility (50% more than
alpha)
• Reduction in neutralization by post
vaccination seraDavis C et al doi: https://doi.org/10.1101/2021.06.23.21259327
Davis C et al doi: https://doi.org/10.1101/2021.06.23.21259327
Vaccine efficacy against Delta in the
field
• Pfizer: Vaccine efficacy of 88% against
symptomatic disease
• AstraZenecac: Vaccine efficay of 67% against
symptomatic disease
• (Davis C et al doi: https://doi.org/10.1101/2021.06.23.21259327)Vaccine efficacy against severe illness caused by Delta variant
Alpha Delta
Stowe J et al Public Health England submitted 2021Summary • Current state of the literature shows that the vaccines licensed in Canada are very safe, trigger an immune response against the SARS-CoV-2 that provides excellent protection against illness, protects against infection and leads to a much reduced viral load and infectivity in breakthrough infection • The vaccine are also effective against the current variants of concerns • Duration of immunity is still uncertain
CBC news and Public Health Agency of Canada July 18, 2021
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