Immunization Update 2021

Abstract

The Advisory Committee on Immunization Practices (ACIP) typically meets three times each year (February, June, and October) to review vaccine-related scientific data and vote on recommendations. In addition, vaccine-specific work groups meet throughout the year to review evidence and develop policy options for ACIP's consideration. The main focus of ACIP since June 2020 has been to review and make recommendations related to the coronavirus disease 2019 (COVID-19) vaccines that have been developed to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Pharmacists have a responsibility to follow immunization guidelines and incorporate best practices into their procedures when administering vaccines. Staying up to date can be challenging as information related to COVID-19 vaccines changes frequently. This article provides an overview of COVID-19 vaccine information as well as an update on vaccine and immunization practices unrelated to COVID-19 made by ACIP during 2020 and 2021. On December 11, 2020, FDA issued an emergency use authorization (EUA) for the Pfizer–BioNTech vaccine as the first COVID-19 vaccine available.1FDA FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 vaccine.www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19Date accessed: June 19, 2021Google Scholar The Pfizer–BioNTech vaccine is messenger RNA (mRNA) that codes for the SARS-CoV-2 surface spike protein encapsulated in a lipid nanoparticle.2Creech CB Walker SC Samuels RJ SARS-CoV-2 vaccines.JAMA. 2021; 325: 1318-1320Crossref PubMed Scopus (141) Google Scholar The lipid nanoparticle protects the mRNA from degradation until it can reach the inside of the cells.2Creech CB Walker SC Samuels RJ SARS-CoV-2 vaccines.JAMA. 2021; 325: 1318-1320Crossref PubMed Scopus (141) Google Scholar When the vaccine enters cells, the mRNA provides the cells with instructions to make copies of the surface spike protein that is unique to the SARS-CoV-2 virus. The body recognizes the spike protein as an antigen and produces antibodies against the protein, eliciting an immune response. When the body has a subsequent exposure to the spike protein, memory cells will recognize the antigen and produce an immune response. The efficacy and safety of the Pfizer–BioNTech vaccine was evaluated in a multinational, placebo-controlled, observer-blinded trial.3Polack FP Thomas SJ Kitchin N et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (4775) Google Scholar The study enrolled 43,448 participants 16 years or older to receive 2 doses, 21 days apart, of placebo (n = 21,728) or a 30-mcg dose of BNT162b2 (n = 21,720). Inclusion criteria comprised healthy participants or those who had stable chronic medical conditions (i.e., infection with HIV, hepatitis B virus, and hepatitis C virus). Exclusion criteria were extensive but key measures included history of COVID-19 infection, immunosuppressive therapy, or diagnosis with an immunocompromising condition. Efficacy was determined by onset of COVID-19 at least 7 days after the second dose. Of 170 confirmed cases of COVID-19, a total of 162 occurred in the placebo group versus 8 in the vaccine group. Vaccine efficacy was calculated at 95% (95% CI 90.3–97.6). A secondary endpoint was incidence of severe COVID-19, with 9 cases observed in the placebo group and 1 in the vaccine group. Safety data show the vaccine was well tolerated. The most commonly reported local reaction was mild to moderate pain at the injection site which usually resolved within 1 to 2 days. The most commonly reported systemic reactions were fatigue and headache. Overall, systemic reactions were reported more often by younger participants (16–55 years) compared to older participants (55 years and older) and more often after the second dose compared to the first dose.3Polack FP Thomas SJ Kitchin N et al.Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.N Engl J Med. 2020; 383: 2603-2615Crossref PubMed Scopus (4775) Google Scholar The efficacy, safety, and immunogenicity of the Pfizer–BioNTech vaccine in adolescents aged 12 to 15 years was evaluated in a multinational, placebo-controlled, observer-blinded trial.4Frenck RW Klein NP Kitchin N et al.Safety, immunogenicity, and efficacy of the BNT162b2 COVID-19 vaccine in adolescents.N Engl J Med. 2021 May 27; (NEJMoa2107456.)Crossref PubMed Scopus (230) Google Scholar The study enrolled 2,260 adolescent participants to receive 2 doses, 21 days apart, of placebo (n = 1,129) or a 30-mcg dose of BNT162b2 (n = 1,131). Immunogenicity was evaluated using noninferiority of the immune response to the vaccine in 12- to 15-year-old participants compared to the immune response in 16- to 25-year-old participants. Inclusion criteria encompassed healthy participants or those who had stable chronic medical conditions (i.e., infection with HIV, hepatitis B virus, and hepatitis C virus). Exclusion criteria included history of COVID-19 diagnosis or SARS-CoV-2 infection, diagnosis with an immunocompromising condition, or immunosuppressive therapy. Sixteen confirmed cases of COVID-19 occurred in the placebo group versus 0 in the vaccine group. Vaccine efficacy was calculated at 100% (95% CI 75.3–100). For the immunogenicity outcome, noninferiority criterion was met as the geometric mean titer in 12- to 15-year-old participants relative to 16- to 25-year-old participants was 1.76 (95% CI 1.47–2.10). This titer represented a greater immune response in the 12- to 15-year-old cohort. Safety data show the vaccine was well tolerated. The most commonly reported location reaction was mild to moderate injection site pain (79%–85%). The most common systemic reactions were fatigue (60%–66%) and headache (55%–65%).4Frenck RW Klein NP Kitchin N et al.Safety, immunogenicity, and efficacy of the BNT162b2 COVID-19 vaccine in adolescents.N Engl J Med. 2021 May 27; (NEJMoa2107456.)Crossref PubMed Scopus (230) Google Scholar On May 10, 2021, FDA updated the Pfizer–BioNTech EUA to include use of the vaccine in adolescents aged 12 to 15 years.5FDA Coronavirus (COVID-19) update: FDA authorizes Pfizer-BioNTech COVID-19 vaccine for emergency use in adolescents in another important action in fight against pandemic.www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-useDate accessed: June 19, 2021Google Scholar On December 18, 2020, FDA issued an EUA for the Moderna vaccine as the second COVID-19 vaccine.6FDA FDA takes additional action in fight against COVID-19 by issuing emergency use authorization for second COVID-19 vaccine.www.fda.gov/news-events/press-announcements/fda-takes-additional-action-fight-against-covid-19-issuing-emergency-use-authorization-second-covidDate accessed: June 19, 2021Google Scholar Similar to the Pfizer–BioNTech vaccine, the Moderna vaccine is mRNA encapsulated in a lipid nanoparticle.2Creech CB Walker SC Samuels RJ SARS-CoV-2 vaccines.JAMA. 2021; 325: 1318-1320Crossref PubMed Scopus (141) Google Scholar The efficacy and safety of the Moderna vaccine was evaluated in a randomized, observer-blinded, placebo-controlled trial.7Baden LR Sahly HM Essink B et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021 Feb 4; 384: 403-416Crossref PubMed Scopus (3083) Google Scholar The study enrolled 30,420 participants 18 years or older to receive 2 doses, 28 days apart, of placebo (n = 15,210) or a 100-mcg dose of mRNA-1273 (n = 15,210). Inclusion criteria comprised participants with no history of SARS-CoV-2 infection, high risk for severe COVID-19, or both. In addition, adults with stable chronic medical conditions were included (i.e., lung disease, heart disease, severe obesity, diabetes, liver disease, or HIV infection).7Baden LR Sahly HM Essink B et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021 Feb 4; 384: 403-416Crossref PubMed Scopus (3083) Google Scholar, 8Moderna clinical study protocol. A phase 3, randomized, stratified, observer-blind, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine in adults aged 18 years and older. ModernaTX, Inc..modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdfDate accessed: June 19, 2021Google Scholar Exclusion criteria included close contact with anyone who tested positive for COVID-19 in the previous month, who were pregnant or breastfeeding, or who participated in another clinical trial in the previous month.8Moderna clinical study protocol. A phase 3, randomized, stratified, observer-blind, placebo-controlled study to evaluate the efficacy, safety, and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine in adults aged 18 years and older. ModernaTX, Inc..modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdfDate accessed: June 19, 2021Google Scholar Efficacy was determined by onset of COVID-19 at least 14 days after the second dose.7Baden LR Sahly HM Essink B et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021 Feb 4; 384: 403-416Crossref PubMed Scopus (3083) Google Scholar Of 196 confirmed cases of COVID-19, a total of 185 occurred in the placebo group versus 11 in the vaccine group. Vaccine efficacy was calculated at 94.1% (95% CI 89.3–96.8; P <0.001). A secondary endpoint was incidence of severe COVID-19, with 30 cases observed in the placebo group and 0 in the vaccine group. Safety data show the vaccine was well tolerated. The most commonly reported local reaction was pain at the injection site which usually resolved within 2 to 3 days. Overall, both local and systemic reactions were reported more often by younger participants (18 years to <65 years) compared to older participants (≥65 years and older) and more often after the second dose compared to the first dose.7Baden LR Sahly HM Essink B et al.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.N Engl J Med. 2021 Feb 4; 384: 403-416Crossref PubMed Scopus (3083) Google Scholar Moderna announced primary efficacy analysis for the mRNA-1273 vaccine in adolescents aged 12 years to less than 18 years in May 2021.9Moderna announces teenCOVE study of its COVID-19 vaccine in adolescents meets primary endpoint and plans to submit data to regulators in early June.investors.modernatx.com/news-releases/news-release-details/moderna-announces-teencove-study-its-covid-19-vaccineDate accessed: June 19, 2021Google Scholar The study enrolled 3,732 participants to receive 2 doses, 28 days apart, of placebo or a 100-mcg dose of mRNA-1273 in a 2:1 ratio. Four confirmed cases of COVID-19 occurred in the placebo group versus 0 in the vaccine group. Vaccine efficacy was calculated at 100%. Vaccine efficacy using a secondary CDC definition for COVID-19 was calculated at 93% starting 14 days after the first dose of vaccine. Immunogenicity data were used to bridge the immune response in adolescents to those of adults. Although no data were published in the press release, the company stated that noninferior immunogenicity in adolescents compared to adults was met. Safety data show the vaccine was well tolerated. The most commonly reported local reaction was injection site pain. The most commonly reported systemic reactions were headache, fatigue, myalgia, and chills.9Moderna announces teenCOVE study of its COVID-19 vaccine in adolescents meets primary endpoint and plans to submit data to regulators in early June.investors.modernatx.com/news-releases/news-release-details/moderna-announces-teencove-study-its-covid-19-vaccineDate accessed: June 19, 2021Google Scholar On June 10, 2021, Moderna filed for an EUA with FDA for their COVID-19 vaccine in adolescents aged 12 years to less than 18 years.10Moderna files for emergency use authorization for its COVID-19 vaccine in adolescents in the United States.investors.modernatx.com/news-releases/news-release-details/moderna-files-emergency-use-authorization-its-covid-19-vaccineDate accessed: June 19, 2021Google Scholar Following initial widespread use of the Pfizer–BioNTech and Moderna COVID-19 vaccines, cases of anaphylaxis after administration of the vaccines began to be reported. Utilizing the Vaccine Adverse Event Reporting System (VAERS), CDC evaluated submitted reports. For the Pfizer–BioNTech vaccine from December 14 to 23, 2020, the initial reporting of anaphylaxis was 21 cases with 1,893,360 first doses of the vaccine (11.1 cases per million doses).11Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine—United States, December 14-23, 2020.MMWR. 2021; 70: 46-51Crossref PubMed Scopus (0) Google Scholar Seventy-one percent of the cases occurred within 15 minutes of vaccination.11Allergic reactions including anaphylaxis after receipt of the first dose of Pfizer-BioNTech COVID-19 vaccine—United States, December 14-23, 2020.MMWR. 2021; 70: 46-51Crossref PubMed Scopus (0) Google Scholar For the Moderna vaccine from December 21, 2020, to January 10, 2021, the initial reporting of anaphylaxis was 10 cases with 4,041,396 first doses of the vaccine (2.5 cases per million doses).12Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020-January 10, 2021.MMWR. 2021; 70: 125-129Crossref PubMed Google Scholar Nine of the 10 cases occurred within 15 minutes of vaccination.12Allergic reactions including anaphylaxis after receipt of the first dose of Moderna COVID-19 vaccine—United States, December 21, 2020-January 10, 2021.MMWR. 2021; 70: 125-129Crossref PubMed Google Scholar Since these initial estimates, millions more doses of both vaccines have been administered. CDC continues to monitor VAERS data for safety signals. An updated report published in JAMA in March 2021 found incidence rates of 4.7 cases/million doses of the Pfizer–BioNTech vaccine and 2.5 cases/million doses of the Moderna vaccine.13Shimabukuro TT Cole M Su JR Reports of anaphylaxis after receipt of mRNA COVID-19 vaccines in the US-December 14, 2020-January 18, 2021.JAMA. 2021 Mar 16; 325: 1101-1102Crossref PubMed Scopus (164) Google Scholar On February 27, 2021, FDA issued an EUA for the Janssen/Johnson & Johnson vaccine as the third COVID-19 vaccine and the first one-dose vaccine.14FDA FDA issues emergency use authorization for third COVID-19 vaccine.www.fda.gov/news-events/press-announcements/fda-issues-emergency-use-authorization-third-covid-19-vaccineDate accessed: June 19, 2021Google Scholar The Janssen/Johnson & Johnson vaccine is a nonreplicating human adenovirus vector vaccine. Adenoviruses are a group of viruses that cause the common cold. This adenovirus was selected because Janssen/Johnson & Johnson used this vector in an Ebola virus vaccine that was recently approved by the European Commission.15National Institutes of Health Fourth large-scale COVID-19 vaccine trial begins in the United States.www.nih.gov/news-events/news-releases/fourth-large-scale-covid-19-vaccine-trial-begins-united-statesDate accessed: June 19, 2021Google Scholar Within the adenovirus, researchers have inserted the gene which codes for the SARS-CoV-2 surface spike protein.16Sadoff J Gray G Vandebosch A et al.Safety and efficacy of single-dose Ad26.CVO2.S vaccine against COVID-19.N Engl J Med. 2021 Jun 10; 384: 2187-2201Crossref PubMed Scopus (665) Google Scholar When the vaccine enters cells, the adenovirus provides the cells with instructions to make copies of the surface spike protein of the SARS-CoV-2 virus. The body recognizes the spike protein as an antigen and produces antibodies against the protein, eliciting an immune response. When the body has a subsequent exposure to the spike protein, memory cells will recognize the antigen and produce an immune response. The efficacy and safety of the Janssen/Johnson & Johnson vaccine was evaluated in an international, randomized, double-blind, placebo-controlled trial.16Sadoff J Gray G Vandebosch A et al.Safety and efficacy of single-dose Ad26.CVO2.S vaccine against COVID-19.N Engl J Med. 2021 Jun 10; 384: 2187-2201Crossref PubMed Scopus (665) Google Scholar The per-protocol analysis included 39,321 participants 18 years and older to receive one dose of placebo (n = 19,691) or a 5 x 1010Moderna files for emergency use authorization for its COVID-19 vaccine in adolescents in the United States.investors.modernatx.com/news-releases/news-release-details/moderna-files-emergency-use-authorization-its-covid-19-vaccineDate accessed: June 19, 2021Google Scholar viral particles dose of Ad26.COV2.S (n = 19,630). Inclusion criteria comprised healthy participants and those with stable chronic medical conditions. In addition, women of childbearing potential required use of appropriate contraception. Exclusion criteria were extensive and included, but were not limited to, severe acute illness, allergic reaction to vaccines or excipients, abnormal immune system function due to medical conditions or medications, receipt of blood products, pregnancy, recent hospitalization, and malignancy. Efficacy was determined by onset of moderate to severe critical COVID-19 at least 14 days after administration of the vaccine. Of the 464 confirmed cases of COVID-19, a total of 348 occurred in the placebo group versus 116 in the vaccine group. Vaccine efficacy was calculated at 66.9% (95% CI 59.0–73.4). Vaccine efficacy at 28 days after vaccine administration was 66.1% (95% CI 55.9–74.8) with 193 cases of COVID-19 in the placebo group and 66 in the vaccine group. The vaccine was well tolerated. In the vaccine group, injection site pain was the most common local reaction (48.6%); the most common systemic reactions were headache (38.9%), fatigue (38.2%), myalgia (33.2%), and nausea (14.2%).16Sadoff J Gray G Vandebosch A et al.Safety and efficacy of single-dose Ad26.CVO2.S vaccine against COVID-19.N Engl J Med. 2021 Jun 10; 384: 2187-2201Crossref PubMed Scopus (665) Google Scholar On April 13, 2021, CDC and FDA jointly recommended a pause in the use of the Janssen/Johnson & Johnson COVID-19 vaccine due to reports of cerebral venous sinus thrombosis (CVST) in combination with thrombocytopenia.17FDA Joint CDC and FDA statement on Johnson & Johnson COVID-19 vaccine.www.fda.gov/news-events/press-announcements/joint-cdc-and-fda-statement-johnson-johnson-covid-19-vaccineDate accessed: June 19, 2021Google Scholar At this point, VAERS data reported 6 cases of CVST with thrombocytopenia among the approximately 7 million doses of vaccine administered.18See I Su JR Lale A et al.US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021.JAMA. 2021 Apr 30; e217517 Google Scholar During the 10-day pause in vaccine administration, an additional 6 cases of thrombosis with thrombocytopenia (TTS) were identified.18See I Su JR Lale A et al.US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021.JAMA. 2021 Apr 30; e217517 Google Scholar ACIP performed a population- and individual-level risk versus benefit analysis related to the incidence of TTS. Population-level modeling data showed resuming use of the Janssen/Johnson & Johnson vaccine among persons 18 years and older could prevent 3,926 to 9,394 COVID-19 related hospitalizations; 928 to 2,236 ICU admissions; and 586 to 1,435 deaths. 19MacNeil JR Su JR Broder RK et al.Updated recommendations rom ACIP for use of Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—U.S. April 2021.MMWR Early Release. April 27, 2021; : 70Google Scholar This was in contrast to 26 expected cases of TTS. On April 23, 2021, after a 10-day pause, ACIP voted in favor of reaffirming their recommendation for the use of the Janssen/Johnson & Johnson COVID-19 vaccine. As a result, FDA has added a warning to the Janssen/Johnson & Johnson COVID-19 vaccine EUA and fact sheets about the incidence of TTS.19MacNeil JR Su JR Broder RK et al.Updated recommendations rom ACIP for use of Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—U.S. April 2021.MMWR Early Release. April 27, 2021; : 70Google Scholar The incidence of TTS has continued to be monitored. As of May 7, 2021, 28 cases of TTS have been reported and confirmed through VAERS after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.20Shimabukuro T Update: Thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Advisory Committee on Immunization Practices Presentation.www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdfDate accessed: June 19, 2021Google Scholar Patient demographics include median age 40 years (range 18–59 years); time from vaccination to symptom onset 9 days (range 3–15 days); and sex (female = 22; male = 6). Incidence of TTS seems to be the highest for females aged 30 to 49 years. In females aged 30 to 39 years, 8 TTS cases were reported within 642,745 vaccine doses for a reporting rate of 12.4 per million doses. In females aged 40 to 49 years, 7 TTS cases were reported within 743,256 vaccine doses for a reporting rate of 9.4 per million doses.20Shimabukuro T Update: Thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Advisory Committee on Immunization Practices Presentation.www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdfDate accessed: June 19, 2021Google Scholar Vaccine providers and the public need to be educated about the risk for TTS and the benefit of vaccination. Women 18 to 49 years can be made aware of the availability of other COVID-19 vaccines. Viruses constantly undergo mutation with new variants expected to occur. Multiple variants of the SARS-CoV-2 virus have been identified in the United States and globally throughout the pandemic. See Table 1 for a list of the variants found in the United States.Table 1U.S. SARS-CoV-2 variantsSource: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/10-COVID-Scobie-508.pdfVariantLocation of first detectionNumber of spike protein mutationsReduced antibody efficacyReduced neutralization by vaccine seraAttributesB.1.526New York3-7YesYesB.1.526.1New York6-8PotentialPotentialB.1.525UK/Nigeria8PotentialPotentialP.2Brazil3-4PotentialYesB.1.617India3PotentialYesB.1.617.1India7-8PotentialPotentialB.1.617.2 (Delta)India9-10PotentialPotentialB.1.617.3India7PotentialPotentialB.1.1.7 (Alpha)UK10-13MinimalMinimal50% increased transmissionB.1.351 (Beta)South Africa10YesYes50% increased transmissionP.1 (Gamma)Japan/Brazil11YesYesB.1.427 (Epsilon)California4ModestYes20% increased transmissionB.1.429 (Epsilon)California4ModestYes20% increased transmission Open table in a new tab The concern with variants is that limited data are available related to vaccine efficacy. A letter to the editor of The New England Journal of Medicine describes a study in Qatar where Pfizer–BioNTech vaccine effectiveness was calculated to be 89.5% (95% CI 85.9–92.3) for the B.1.1.7 variant and 75% (95% CI 70.5–78.9) for the B.1.351 variant.21University of Oxford About the Oxford COVID-19 vaccine.www.research.ox.ac.uk/article/2020-07-19-the-oxford-covid-19-vaccineDate accessed: June 19, 2021Google Scholar ChAdOx1 is a nonreplicating chimpanzee adenovirus vector vaccine. This adenovirus was selected because it is known to generate a strong immune response from one dose when used for other vaccines.22Abu-Raddad LJ Chemaitelly H Butt AA Effectiveness of the BNT162b2 COVID-19 vaccine against the B.1.1.7 and B.1.351 variants.N Engl J Med. 2021 May 5; (NEJMc2104974.)Crossref PubMed Scopus (356) Google Scholar The efficacy and safety of the AstraZeneca/University of Oxford vaccine was evaluated in an international, blinded, randomized, controlled trial.23Voysey M Clemens SA Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021 Jan 9; 397: 99-111Abstract Full Text Full Text PDF PubMed Scopus (1878) Google Scholar This interim analysis included 11,636 participants of the 23,848 total participants enrolled in 2 of 4 clinical trials. Participants 18 years and older received 2 doses, 28 days apart, of 5 x 1010Moderna files for emergency use authorization for its COVID-19 vaccine in adolescents in the United States.investors.modernatx.com/news-releases/news-release-details/moderna-files-emergency-use-authorization-its-covid-19-vaccineDate accessed: June 19, 2021Google Scholar viral particles per dose of ChAdOx1 or control (meningococcal ACWY conjugate vaccine or placebo). A subset of patients in the United Kingdom trial received a half dose followed by a full dose 28 days apart. Efficacy was determined by onset of COVID-19 at least 14 days after the second dose. Of the 131 confirmed cases of COVID-19, a total of 101 occurred in the control/placebo group and 30 occurred in the vaccine group. Vaccine efficacy for the 2-dose regimen was calculated at 62.1% (95% CI 41.0–75.7). Vaccine efficacy for the half-dose followed by full-dose regimen was calculated at 90% (95% CI 67.4–97.0). Combined vaccine efficacy for both dosing regimens was calculated at 70.4% (95.8% CI 54.8–80.6) An additional endpoint of no cases of severe COVID-19 was reported.23Voysey M Clemens SA Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021 Jan 9; 397: 99-111Abstract Full Text Full Text PDF PubMed Scopus (1878) Google Scholar Although a variety of adverse events were reported in the trials, review of the safety data did not find a pattern linking these events to the vaccine. Overall, both doses of the vaccine were well tolerated. On December 30, 2020, the vaccine received emergency approval in the United Kingdom but AstraZeneca has not submitted a request to FDA for an EUA in the United States.24AstraZeneca AstraZeneca's COVID-19 vaccine authorized for emergency supply in UK.www.astrazeneca.com/media-centre/press-releases/2020/astrazenecas-covid-19-vaccine-authorised-in-uk.htmlDate accessed: June 19, 2021Google Scholar NVX-CoV2373 is a recombinant SARS-CoV-2 spike protein nanoparticle vaccine which contains the Matrix-M adjuvant.2Creech CB Walker SC Samuels RJ SARS-CoV-2 vaccines.JAMA. 2021; 325: 1318-1320Crossref PubMed Scopus (141) Google Scholar A cell-based system is used to produce copies of the SARS-CoV-2 spike protein subunit which are bound together into a nanoparticle. When the vaccine enters cells, the nanoparticle releases the protein subunits. The body recognizes the spike protein as an antigen and produces antibodies against the protein, eliciting an immune response. When the body has a subsequent exposure to the spike protein, memory cells will recognize the antigen and produce an immune response. The efficacy, immunogenicity, and safety of the Novavax vaccine was evaluated in a phase 3, randomized, observer-blinded, placebo-controlled trial.25Clinicaltrials.govGoogle ScholarNovavax clinical study protocol. A study to evaluate the efficacy, immune response, and safety of a COVID-19 vaccine in adults ≥ 18 years with a pediatric expansion in adolescents (12-17 years) at risk for SARS-CoV-2.clinicaltrials.gov/ct2/show/NCT04611802?term=NCT04611802&draw=2&rank=1Date accessed: June 19, 2021Google Scholar The study enrolled 29,960 participants 18 years or older to receive 2 doses, 21 days apart, of placebo or a 5-mcg dose of NVX-CoV2373 in a 1:2 ratio. Inclusion criteria encompassed participants considered at increased risk for exposure to and infection with SARS-CoV-2, women of childbearing potential abstaining from heterosexual intercourse or use of contraception, and those deemed medically stable by investigators. Exclusion criteria included unstable acute or chronic illness, participation in another investigational study, history of SARS-CoV-2 infection or COVID-19, immunosuppression via disease or drug therapy, active cancer, pregnancy or breastfeeding, and receipt of blood or blood products.25Clinicaltrials.govGoogle ScholarNovavax clinical study protocol. A study to evaluate the efficacy, immune response, and safety of a COVID-19 vaccine in adults ≥ 18 years with a pediatric expansion in adolescents (12-17 years) at risk for SARS-CoV-2.clinicaltrials.gov/ct2/show/NCT04611802?term=NCT04611802&draw=2&rank=1Date accessed: June 19, 2021Google Scholar Efficacy was determined by onset of symptomatic COVID-19 after 7 or more days post second dose.26NIH US clinical trial results show Novavax vaccine is safe and prevents COVID-19.www.nih.gov/news-events/news-releases/us-clinical-trial-results-show-novavax-vaccine-safe-prevents-covid-19Date accessed: June 19, 2021Google Scholar Of the 77 confirmed cases of COVID-19, a total of 63 occurred in the placebo group and 14 occurred in the vaccine group. Vaccine efficacy in preventing symptomatic COVID-19 was calculated at 90.4% (95% CI 82.9–94.6).26NIH US clinical trial results show Novavax vaccine is safe and prevents COVID-19.www.nih.gov/news-events/news-releases/us-clinical-trial-results-show-novavax-vaccine-safe-prevents-covid-19Date accessed: June 19, 2021Google Scholar, 27Novavax Novavax COVID-19 vaccine demonstrates 90% overall efficacy and 100% protection against moderate and severe disease in PREVENT-19 phase 3 trial.ir.novavax.com/news-releases/news-release-details/novav