Shay , MD 1 On October 29, 2021, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccine to expand its use to children aged 5–11 years, administered as 2 doses (10 μ g, 0.2mL each) 3 weeks apart ( 1 ). As of December 19, 2021, only the Pfizer-BioNTech COVID-19 vaccine is authorized for administration to children aged 5–17 years ( 2 , 3 ). In preauthorization clinical trials, Pfizer-BioNTech COVID-19 vaccine was administered to 3,109 children aged 5–11 years; most adverse events were mild to moderate, and no serious adverse events related to vaccination were reported ( 4 ). To further characterize safety of the vaccine in children aged 5–11 years, CDC reviewed adverse events after receipt of Pfizer-BioNTech COVID-19 vaccine reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system co-managed by CDC and FDA, and adverse events and health impact assessments reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination,* during November 3–December 19, 2021. Myocarditis is a rare and serious adverse event that has been associated with mRNA-based COVID-19 vaccines; reporting rates for vaccine-associated myocarditis appears highest among males aged 12–29 years ( 8 ). To date, myocarditis among children aged 5–11 years appears rare; 11 verified VAERS reports have been received after administration of approximately eight million vaccine doses, and, in an active vaccine safety surveillance system, no chart-confirmed reports of myocarditis were observed during the 1–21 days or 1–42 days after 333,000 vaccine doses were administered to children of the same age (6 ) These cases appear consistent with other reports of myocarditis after mRNA COVID-19 vaccination regarding time to symptom onset and a mild clinical course (9 ). Two deaths after Pfizer-BioNTech COVID-19 vaccine were reported for children with multiple chronic medical conditions; on initial review, no data were found that would suggest a causal association between death and vaccination.

As noted by a recent piece in The New England Journal of Medicine , “we look to vaccines to give us back our world”. On May 10, 2021, the US Food and Drug Administration expanded its emergency use authorisation for the Pfizer-BioNtech mRNA COVID-19 vaccine (BNT162b2) in adolescents aged 12–15 years.2 Centers for Disease Control and Prevention Acceptability of adolescent COVID-19 vaccination among adolescents and parents of adolescents—United States, April 15–23, 2021. Google Scholar A survey, done in the USA between April 15 and April 23, 2021, by the Centers for Disease Control and Prevention (CDC), found that only 55·5% of 1022 parents and guardians of unvaccinated adolescents aged 12–17 years would “definitely” or “probably” allow their child to receive a COVID-19 vaccine, and only 51·7% of 985 adolescents aged 13–17 years would “definitely” or “probably” receive a COVID-19 vaccine.2 Centers for Disease Control and Prevention Acceptability of adolescent COVID-19 vaccination among adolescents and parents of adolescents—United States, April 15–23, 2021.

A pandemic vaccine adjuvant will be available to enhance development [2] . CEPI has also launched a call for organisations with large manufacturing capabilities for vaccine candidates, to advance an effective vaccine and transfer the vaccine platform to a global network of large-scale manufacturing [2] . There are currently 21 COVID-19 vaccines candidates in clinical trials, including four funded by CEPI (including the mRNA (the first to enter clinical trials, co-developed with the National Institute of Allergy and Infectious Diseases (NIAID), USA), DNA, ChAdOx1-S and protein subunit vaccine) as shown in Table 1 [4] , [5] . Table 2 shows the candidates in preclinical development [4] , [5] . Table 1 . COVID-19 Vaccine Candidates in Clinical Development (21 as of June 29, 2020). Vaccine Candidate Platform Phase of Clinical Development Developer ChAdOx1-S expressing S protein Non Replicating Viral Vector Phase 3 University of Oxford, AstraZeneca Adenovirus Type 5 Vector expressing S protein Non Replicating Viral Vector Phase 2 CanSino Biological Inc., Beijing Institute of Biotechnology Lipid nanoparticle (LNP) encapsulated mRNA encoding S protein RNA Phase 2 Moderna, NIAID Inactivated Inactivated Phase 1/2 Beijing Institute of Biological Products, Sinopharm Inactivated Inactivated Phase 1/2 Wuhan Institute of Biological Products, Sinopharm Inactivated with alum Inactivated Phase 1/2 Sinovac Full length recombinant SARS CoV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M Protein Subunit Phase 1/2 Novavax 3 LNP-mRNAs RNA Phase 1/2 BioNTech, Fosun Pharma, Pfizer Inactivated Inactivated Phase 1/2 Institute of Medical Biology, Chinese Academy of Medical Sciences Adeno-based Non Replicating Viral Vector Phase 1 Gamaleya Research Institute DNA plasmid encoding S protein delivered by electroporation DNA Phase 1 Inovio Pharmaceuticals DNA Vaccine (GX-19) DNA Phase 1 Genexine Consortium LNP-nCoVsaRNA Self-amplifying RNA Phase 1 Imperial College London mRNA RNA Phase 1 Curevac mRNA RNA Phase 1 People's Liberation Army (PLA) Academy of Military Sciences, Walvax Biotech S-Trimer subunit vaccine adjuvanted Protein Subunit Phase 1 Clover Biopharmaceuticals, GSK, Dynavax Adjuvanted recombinant protein (RBD Dimer) Protein Subunit Phase 1 Anhui Zhifei Longcom Biopharmaceutical, Institute of Microbiology, Chinese Academy of Sciences Autologous Dendritic Cells with SARS-CoV-2 antigens, administered with granulocyte–macrophage colony-stimulating factor (GM-CSF) Dendritic cell vaccine Phase 1 Aivita Biomedical Dendritic cells (DC) modified with lentivirus vector, expressing synthetic minigene based on domains of selected viral proteins, administered with antigen specific cytotoxic T lymphocytes (CTLs) Modified DC Phase 1 Shenzhen Geno-Immune Medical Institute Artificial antigen-presenting cells (aAPCs) modified with lentiviral vector, expressing synthetic minigene based on domains of selected proteins Modified APCs Phase 1 Shenzhen Geno-Immune Medical Institute bac-TRL Spike, orally delivered Live Bifidobacterium longum to deliver plasmids of synthetic DNA encoding SARS-CoV-2 spike protein Phase 1 Symvivo Source- ClinicalTrials.gov, London School of Hygiene and Tropical Medicine [4] , WHO [5] . Table 2 . COVID-19 Vaccine Candidates in Pre-Clinical Development (estimated to be 182 as of June 29, 2020). Vaccine Platform Examples of Types of Vaccines Estimated Number of Vaccine Candidates Live-attenuated vaccines • Codon deoptimized • Measles Virus (S, N targets) 3 Inactivated • Inactivated • Inactivate whole virus • Inactivated + CpG 1018 6 Non-replicating viral vectors • Modified Vaccinia Ankara (MVA) encoded Virus Like Particles (VLP) • MVA expressing structural proteins • MVA-S • MVA-S encoded • Adenovirus-based NasoVAX expressing SARS2-CoV spike protein • Adenovirus 26 (Ad26) (alone or with MVA boost) • Adeno-associated virus vector (AAVCOVID) • Adeno-associated virus • Ad5 S (GREVAXplatform) • Oral Ad5 S • Adenovirus-based + HLA-matched peptides • Replication defective Simian Adenovirus (GRAd) encoding SARS-CoV-2 S • Influenza A H1N1 vector • Parainfluenza virus 5 (PIV5)-based vaccine expressing the spike protein • Recombinant deactivated rabies virus containing S1 • [E1-, E2b-, E3-] hAd5- COVID19- Spike/Nucleocapsid • Inactivated Flu-based SARS-CoV2 vaccine + Adjuvant • Dendritic cell-based • Oral vaccine in tablet formulation 21 Replicating viral vectors • Measles • Measles (S, N targets) • Horsepox vector expressing S protein • YF17D • Live viral vectored vaccine based on attenuated influenza virus backbone (intranasal) • Recombinant vaccine based on Influenza A virus, for the prevention of COVID19 (intranasal) • Attenuated Influenza expressing an antigenic portion of the Spike protein • Influenza vector expressing RBD • M2-deficient single replication (M2SR) influenza vector • Vesicular Stomatitis Virus (VSV) • VSV-S • Replication competent VSV chimeric virus technology (VSVΔG) delivering the SARSCoV-2 Spike (S) glycoprotein • Newcastle disease virus vector (NDVSARS-CoV-2/Spike) • Avian paramyxovirus vector (APMV) 17 Protein Subunit • Protein Subunit • Protein Subunit S,N,M and S1 protein • RBD protein fused with Fc of IgG + Adj • S1 or RBD protein • RBD based • RBD protein fused with Fc of IgG with Adjuvant • Capsid-like Particle • Drosophila S2 insect cell expression system VLPs • Peptide antigens formulated in LNP • Peptides derived from Spike protein • Peptide • S protein • S protein with adjuvant • Microneedle arrays S1 subunit • Spike-based • Spike-based (epitope screening) • Adjuvanted protein subunit (RBD) • Ii-Key peptide • Protein Subunit EPVCoV-19 • gp-96 backbone • Molecular clamp stabilized Spike protein • Subunit • Subunit protein, plant produced • Subunit protein, baculovirus produced • Recombinant protein, nanoparticles (based on S-protein and other epitopes) • COVID-19 XWG-03 truncated S (spike) proteins • Adjuvanted microsphere peptide • Synthetic Long Peptide Vaccine candidate for S and M proteins • Oral E. coli-based protein expression system of S and N proteins • Nanoparticle • Recombinant spike protein with Advaxadjuvant • VLP-recombinant protein with adjuvant • Plant-based subunit (RBD-Fc + Adjuvant) • Structurally modified spherical particles of the tobacco mosaic virus (TMV) • Recombinant S1-Fc fusion protein • Recombinant protein • Recombinant S protein in IC-BEVS • Orally delivered, heat stable subunit • S-2P protein + CpG 1018 • Outer Membrane Vesicle (OMV)-subunit • OMV-based vaccine • Outer Membrane Vesicle(OMV)-peptide 59 Virus-like Particle (VLP) • S protein integrated in HIV VLPs • VLP with Adjuvant • VLP, lentivirus and baculovirus vehicles • VLP, based on RBD displayed on VLPs • Enveloped VLP • Plant-derived VLP • ADDomerTM multiepitope display • VLPs peptides/whole virus 10 DNA • DNA with electroporation • DNA plasmid vaccine • DNA plasmid vaccine S,S1,S2,RBD and N • DNA • Plasmid DNA, Needle Free Delivery • bacTRL-Spike 12 RNA • LNP-encapsulated mRNA • LNP-encapsulated mRNA cocktail encoding VLP • LNP-encapsulated mRNA encoding RBD • Liposome encapsulated mRNA • Replicating Defective SARS-CoV-2 derived RNAs • mRNA • mRNA in an intranasal delivery system 21 Other/ Unknown 43 Source- London School of Hygiene and Tropical Medicine [4] , WHO [5] . The US Government’s Biomedical Advanced Research and Development Authority (BARDA) is funding the development and manufacturing of the ChAdOx1-S vaccine, the Phase 2 and 3 trials for the mRNA vaccine and the developed of recombinant vesicular stomatitis virus (rVSV), Adenovirus 26 (Ad26) and RNA vaccine candidates (in preclinical development). The US Department of Defense and other country governments are also funding vaccine development and manufacturing. CEPI has funded the Brighton Collaboration Safety Platform for Emergency vACcines (SPEAC) project to harmonize the safety of its candidate vaccines, including COVID 19 [8] . The Brighton Collaboration has developed standard templates for benefit risk assessment of vaccine technologies for the main COVID 19 platforms (nucleic acid, protein, viral vector, inactivated viral, and live attenuated viral vaccines) [8] , [9] . The World Health Organization Global Advisory Committee on Vaccine Safety (GACVS) has recommended that any review of the safety of new vaccines be based on these templates as they offer a structured approach to evaluating safety [10] . Adverse Events of Special Interest (AESIs) (serious or non-serious) are events of significant medical and scientific concern specific to the sponsor’s program or product.

All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12–17-year-old children between June 15th , 2021 and January 1st , 2022, were reported. Interpretation Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12–17-year-old children.

Safety of vaccines administered during pregnancy needs to be evaluated for both the mother and her newborn, and is an important consideration for the mothers’ willingness to receive a vaccine during pregnancy [1 ]. There is a significant bulk of evidence to support the safety of immunization with tetanus toxoids, the longest standing vaccine recommended during pregnancy [1 ]. There is also an increasing body of evidence to support the safety of pertussis and influenza immunization during pregnancy [1 ]. Generally, new vaccines are not designed for use during pregnancy; pregnant women are not included in the initial vaccine research; and studies about the efficacy, safety, and tolerability of vaccines in pregnant women are carried out only when there is already substantial evidence that the vaccines could be potentially useful for the mother–child dyad or at least for one of them [8 ]. What has been documented during the current coronavirus disease 2019 (COVID-19) pandemic is representative in this regard. Because of this, it is suggested that these vaccines are given to young, healthy adults only after older people and the population of any age at risk, because of more frequent exposure to the virus or suffering from a chronic severe disease, have already been immunized [21 ,22 ,23 ]. To strongly recommend early vaccination of pregnant women regardless of whether or not they have an underlying diseases, evidence should be available that pregnant women infected by SARS-CoV-2 are at increased risk of developing a more severe disease and/or that pregnancy can be characterized by a higher incidence of complications and/or that the fetus and/or the neonate can have a number of relevant clinical problems. 2.1.

More than 60 million doses of vaccination have been administered to children aged 12–17 years in China [27 ]. Table 1 Seven COVID-19 vaccines approved by WHO for emergency use [17 ,18 ,19 ,20 ,21 ,22 ,23 ,24 ] Full size table The immune system of children, especially infants, is in the process of continuous development and improvement, and the relevant application data of COVID-19 vaccines are limited at present, which needs to be confirmed by more clinical trials. Children who have been previously diagnosed with COVID-19 In principle, one dose of the COVID-19 vaccine can be administered after 6 months of infection [28 ]. Use of intravenous immunoglobulins The use of intravenous immunoglobulins may affect the efficacy of some live attenuated vaccines, but has no effect on inactivated SARS-CoV-2 vaccines [32 ]. Adverse reactions and treatment after COVID-19 vaccination in children [8 , 13 , 14 , 33 ,34 ,35 ,– 36 ] Common adverse reactions and treatment Most of the adverse reactions of the COVID-19 vaccination are mild to moderate and resolved within 24 h after vaccination.

However, the initial messenger RNA (mRNA) vaccine clinical trials excluded several vulnerable groups, including young children and lactating individuals.1 The US Food and Drug Administration deferred the decision to authorize COVID-19 mRNA vaccines for infants younger than 6 months until more data are available because of the potential priming of the children’s immune responses that may alter their immunity.2 The Centers for Disease Control and Prevention recommends offering the COVID-19 mRNA vaccines to breastfeeding individuals,3 although the possible passage of vaccine mRNAs in breast milk resulting in infants’ exposure at younger than 6 months was not investigated. The vaccine detection limit was 1 pg/mL of EBM (eMethods in the Supplement ). Of 11 lactating individuals enrolled, trace amounts of BNT162b2 and mRNA-1273 COVID-19 mRNA vaccines were detected in 7 samples from 5 different participants at various times up to 45 hours postvaccination (Table 2 ). The mean (SD) yield of EVs isolated from EBM was 9.110 (5.010 ) particles/mL, and the mean (SD) particle size was 110.0 (3.0) nm.

Email: ozgurkasapcopur@hotmail.com Search for more papers by this author First published: 03 January 2022 Citations: 3 Abstract Objective Considering the concerns regarding the coronavirus disease-2019 (COVID-19) vaccine safety among pediatric patients with inflammatory rheumatic diseases (IRD) due to a lack of data, an urgent need for studies evaluating safety profiles of vaccines emerged. Methods Among participants vaccinated by CoronaVac inactive SARS-CoV-2 or BNT162b2 messenger RNA (mRNA) COVID-19 (Pfizer-BioNTech) vaccine, healthy children under 18 and patients under 21 with an at least 1-year follow-up period in our department for a childhood-onset rheumatic disease were included into this cross-sectional study.

When SARS-CoV-2 entered the United States early in 2020, children accounted for fewer than 3% of cases; today, they account for more than 25%. More than 6 million US children have been infected with SARS-CoV-2, including 2 million between the ages of 5 and 11. And because the dose of Pfizer’s mRNA is one-third that given to older adolescents, myocarditis in the younger age group will likely be even rarer.

The primary objectives were to determine the safety and reactogenicity of two injections of the selected dose of mRNA-1273 vaccine, administered 28 days apart, and to infer efficacy on the basis of the noninferiority of serum antibody levels and serologic response as compared with those among young adults (18 to 25 years of age) from the randomly selected immunogenicity subgroup of the phase 3 COVE trial.1 Key secondary objectives were to determine the incidences of confirmed Covid-19 and SARS-CoV-2 infection (regardless of symptoms) after administration of the mRNA-1273 vaccine or placebo (Table S1). Safety Evaluations of reactogenicity included assessment of solicited local and systemic adverse reactions that occurred within 7 days after each injection, as recorded in electronic diaries by the parents or guardians of the participants. In part 2 of the trial, for the secondary efficacy objective of determining the incidences of Covid-19 and SARS-CoV-2 infection, regardless of symptoms, we evaluated all randomly assigned participants who did not have serologic or virologic evidence of SARS-CoV-2 infection at baseline and who received at least one planned injection, excluding those who received an incorrect injection (the modified-intention-to-treat-1 population, hereafter called the mITT1 population) and those who received both injections of trial vaccine according to the schedule, without a major protocol deviation (the per-protocol population). Incidence rates, which were calculated as the number of cases divided by the number of person-years (defined as the total years from the first day of the analysis to the date of the event, to the last date of trial participation, to censoring time, or to the efficacy data-cutoff date, whichever was earliest) accrued during the blinded phase before unblinding, and 95% confidence intervals were calculated with the exact method (Poisson distribution). Results Trial Population Between March and August 2021, a total of 751 participants who were 6 to 11 years of age were enrolled in part 1 of the trial and 4016 participants were enrolled in part 2.