Covid 19 vaccines: state of art

Technological advances that merged to develop a COVID-19 vaccine.

Rino Rappuoli et al. PNAS 2021;118:3:e2020368118

©2021 by National Academy of Sciences

Covid-19 Vaccines: a state of art

Titolo Presentazione

Rino Rappuoli et al. PNAS 2021;118:3:e2020368118

Overview of the stages of vaccine clinical development.

Testing of potential vaccine candidates begins in animals in preclinical trials. Once data supporting the safety are established, the first in human studies begin (phase 1) Most pediatric vaccine clinical trials begin in phase 2. Phase 3 studies provide data supporting the safety in large numbers of individuals and typically demonstrate whether the vaccine works in preventing disease (efficacy). Effectiveness and safety in the general population is evaluated in postlicensure phase 4 studies..

Twelve candidate vaccines currently in Phase III trial. COVID-19 Vaccines based on Spike protein DNA carried by adenoviruses.

state

Twelve candidate vaccines currently in Phase III trial. COVID-19 Vaccines based on Spike protein DNA carried by adenoviruses.

Technical summary of the current coronavirus disease 2019 vaccines

COVID-19 vaccines in development and their timeline to clinical testing in humans.

Timing and Distribution of Myocarditis after Receipt of the BNT162b2 Vaccine.

Myocarditis and Other Cardiovascular Complications of the mRNA-Based

Electrocardiogram (ECG) and cardiac magnetic resonance imaging (CMR) findings corresponding to a case of adverse events. ECG shows diffuse ST elevations. B. 4 chamber cine. C. T1 imaging demonstrates regional elevation in the lateral wall (between the arrows). D. T2 mapping shows elevated T2 values in the lateral wall (between the arrows). E. Late gadolinium enhancement imaging shows subepicardial enhancement (between the arrows) in the same areas of T1 and T2 elevations.

PredictedbenefitsofreductioninCOVID-19–relatedhospitalizationsand deathandrisksofmyocarditisafterseconddoseofmRNACOVID-19 vaccinationbyagegroup.

PotentialriskofmyocarditiswithCOVID-19mRNAvaccinationinthe120 daysaftervaccinationandpredictedpreventionofCOVID-19cases,COVID19–relatedhospitalizations,intensivecareunitadmissions,anddeaths accordingtoagegroupsandsex.

The generation of an immune response to a vaccine.

Overview of the humoral immune response to SARS-CoV-2

p

pa of thevaccination schedule,thereare asyet no vaccineeffectivenessdatafor mRNA-1273from theUK.PublicHealth

England reported on theearly impact and effectivenessof COVID-19vaccination

compared with thevaccination coveragein thegeneral population from which thecases arederived).Usingvaccination coverage asthecontrol can producemorereliable information on vaccineeffectiveness,

non-pharmaceutical

interventions

Factors influencing vaccine effectiveness

Unsurprisingly,both antibody resp and vaccineeffectiveness24 arelow after asingledoseof either BNT16 mRNA-1273than after twodoses. levelsfollowingBNT162b2vaccin wanewithin 12weeksfollowingon

Demographic factors

High levelsof circulating virus

Closeproximityof people living together

Host factors

Old age

Previousinfection

Immunecompromise

Genetic polymorphisms

Underlying health conditions

High levelsof vaccineuptake

High levelsof herd immunity

Vaccine accessfactors

Which vaccineused

Number of doses

Timing between doses

Heterologousprime–boost

national vaccinebodies

Limited accessto vaccines

Thereis,however,protection from vaccinedose, with vaccineeffectiv after asingledoseof BNT162b2o and after asingledoseof AZD122

Viral variant factors

Antigenic mismatch with vaccine

Increased transmissibility

Immune factors

High antibodytitres

Qualityof antibody (neutralization)

Tcells

Fig.1|Factorsinfluencingvaccineeffectiveness.Multiplefactorscanincreaseordecreasevaccine effectiveness(VE)at boththeindividual level andthepopulationlevel.

Covid-19 Vaccines: a state of art.

Oneadvantageof delayingvaccina that antibodyresponsesto theseco might begreater;theantibody res BNT162b2isgreater in individual 80yearsor older when thevaccina isincreased from 3to 12weeks25.U thelength of thedoseinterval com toadecision by national vaccinec asto whether it isbetter to get alo level of immuneprotection in agr number of peopleor moreprotecti fewer people.Thisrisk–benefit pr changeover time,especially once coveragehasbeen achieved in the moreat risk groups,but also in res totheemergenceof new viral vari (TABLE 2).In June2021, individuals 40yearsor older in theUK werein toscheduletheir second vaccinati 8weeksrather than 12weeksasca

Delta(B.1.617.2) variant increased important factor that must beincl any risk–benefit calculationsisthe seriousadverseeffectsassociated w vaccines(BOX1).

626–636 (2021) 20

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Covid-19 Vaccines: a state of art.

Covid-19 Vaccines: a state of art.

Association between ANTI-SARS-COV-2 Antibodies and Ag-specific-cells

The presence of specific SARS-CoV-2 B &T cell is associated with the development of antibodies and neutralizing activity (PRNT). This methd was used to evaluate immunogenicity of the vaccine

Early development

nAb

of the

response correlates with viral control and survival.

Efficacy of Pfizer Vaccine in Healthy HC workers

Efficacy of Pfizer Vaccine in Healthy HC workers

Primary Immunodeficiencies

Characteristics of patients with primary immunodeficiencies

CONVERS STUDY

Differences in vaccine responses among different cohorts of vulnerable groups (Inborn Errors of Immunity

SARS CoV2-Cellular Immune responses in children and young adults with IEI

SARS-CoV2 Specific T cell response

• Il 70% dei pazienti con titolo anticorpale assente (IgG < 0.8 U/mL) è in terapia con regimi terapeutici che includono

• L’analisi dell’immunofenotipo linfocitario nei pazienti TX con distinta risposta umorale non mostra differenze statisticamente significative (P value CD3+ 0.5129; p value CD4+ 0,4761; p value CD19+ 0,6567).

SARS-CoV2 Specific T cell response

Cell subsets analysis

B cell phenotype analysis showed similar frequencies of total CD19+ B cells, however the analysis of maturational B cell subsets showed a lower frequency of memory B cell (CD19+CD27+CD21+) in NR compared to NR (p=0.008) (Fig. 4A). This data was also confirmed by a lower frequency of IgD-CD27+ switched memory B cell (p=0.002).

DOI:10.1002/pd.5985

A reasonedapproachtowardsadministeringCOVID‐19

vaccinestopregnant women

Angsumita Pramanick1,2 | AbhiramKanneganti1 | JingLinJeslynWong1,2 | SarahWeilingLi1,2 | Pooja Sharma Dimri1 | Aniza Puteri Mahyuddin2 | SaileshKumar3,4 | Sebastian Enrique Illanes5 | Jerry Kok YenChan6,7 | LinLinSu1,2 | Arijit Biswas1,2 | Paul Anantharajah Tambyah8 | Ruby Yun‐JuHuang9 | CitraNurfarah Zaini Mattar1,2 | MaheshChoolani1,2

1Department of Obstetricsand Gynaecology, National University Hospital Singapore, Singapore

2Department of Obstetricsand Gynaecology, YongLoo Lin School of Medicine,National University of Singapore,Singapore

3Mater Research Institute‐University of Queensland,South Brisbane,Queensland, Australia

4Faculty of Medicine,TheUniversity of Queensland,Herston,Queensland, Australia

5Department of Obstetrics& Gynaecology, Faculty of Medicine,Universidad delosAndes, Santiago,Chile

6Department of Reproductive Medicine,KK Women'sand Children'sHospital,Singapore

7Academic Clinical Program in Obstetricsand Gynaecology,Duke‐NUSMedical School, Singapore

8InfectiousDiseasesTranslational Research Programme,Department of Medicine,Yong Loo Lin School of Medicine, National University of Singapore,Singapore

9School of Medicine, Collegeof Medicine, National Taiwan University, Taipei,Taiwan

Correspondence

Mahesh Choolani, Department of Obstetrics and Gynaecology, NUHSTower Block,Level 12,1EKent Ridge Road, Singapore 119228. Email: obgmac@nus.edu.sg

Abstract

There are over 50 SARS‐CoV‐2 candidate vaccines undergoing Phase II and III clinical trials. Several vaccines have been approved by regulatory authorities and rolledout for useindifferent countries.Duetoconcernsof potential teratogenicity or adverse effect on maternal physiology, pregnancy hasbeen aspecific exclusion criterion for most vaccinetrialswithonlytwotrialsnot excludingpregnant women. Thus, other than limited animal studies, gradually emerging development and reproductivetoxicity data,andobservational datafromvaccineregistries,thereisa paucityofreliableinformationtoguiderecommendationsfor thesafevaccinationof pregnant women. Pregnancy is a risk factor for severe COVID‐19, especially in women with comorbidities, resulting in increased rates of preterm birth and maternal morbidity.Wediscussthemajor SARS‐CoV‐2 vaccines,their mechanisms of action,efficacy,safety profileandpossiblebenefitstothematernal‐fetal dyadto create a rational approach towards maternal vaccination while anticipating and mitigatingvaccine‐relatedcomplications.Pregnant womenwithhighexposurerisks or co‐morbiditiespredisposing to severe COVID‐19 infection should beprioritised for vaccination. Those with risk factors for adverse effects should be counselled accordingly.It isessential to support patient autonomy by shared decision‐making involving arisk‐benefit discussion with the pregnant woman.

Key points

What isalready known about thistopic?

✏COVID‐19 infection in pregnancy leadsto an increase in adverse maternal outcomes.

✏Owing to paucity of data regarding SARS‐CoV‐2 vaccine use in pregnancy there isuncertainty regarding safety of useand subsequent pregnancy outcomes.

Angsumita Pramanick and Abhiram Kanneganti are co‐first authors.

Thisisan open accessarticle under thetermsof theCreative CommonsAttribution‐NonCommercial‐NoDerivsLicense, which permitsuseand distribution in any medium, provided the original work isproperly cited, the use isnon‐commercial and no modifications or adaptations are made.

© 2021 The Authors. Prenatal Diagnosis published by John Wiley & SonsLtd.