We reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, we described the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety, and the role of new SARS-CoV-2 variants on vaccine efficacy

Anwer, Javaria, MBBS

Carrico, Ruth M, PhD, DNP

Eladely, Ahmed A

Glynn, Alex, MA

Gotimukul, Ashwini, MBBS

KC, Manish, MBBS

Petrey, Jessica, MSLS

Ramirez, Julio A, MD

English

University of Louisville

University of Louisville Journal of Respiratory InfectionsBRIEF REVIEWAn Update on the Leading COVID-19 VaccinesAhmed Eladely1, MBBCh; Javaria Anwer1, MBBS; Ashwini Gotimukul1, MBBS; Manish KC1, MBBS; Jessica Petrey2, MSLS; Alex Glynn1, MA;Ruth Carrico1, PhD DNP; Julio A. Ramirez1*, MD1Center of Excellence for Research in Infectious Diseases, Division of Infectious Diseases, University of Louisville, Louisville, KY, USA; 2Kornhauser Sciences Library,School of Medicine, University of Louisville, Louisville, KY, USA*j.ramirez@louisville.eduRecommended Citation: Eladely A, Anwer J, Gotimukul A, et al. An update on the leading COVID-19 vaccines. Univ Louisville J Respir Infect 2021; 5(1): Article 2.AbstractWe reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, wedescribed the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety,and the role of new SARS-CoV-2 variants on vaccine efficacy.IntroductionThere are exceptional ongoing efforts to develop effec-tive vaccines against SARS-CoV-2 with the goal to con-trol the current COVID-19 pandemic. According to theWorld Health organization, as of March 1, 2021, thereare 182 vaccines in preclinical development and 74 vac-cines in different phases of clinical development.[1]We performed a literature review with the objective toevaluate the vaccine efficacy, safety and technology ofthe COVID-19 vaccines that have reached phase III ofclinical development.MethodsVaccines that reached phase III of clinical developmentCOVID-19 vaccines that had reached phase III of clini-cal development were identified. These vaccines wereclassified in two groups: the vaccines that completedphase III studies (no longer recruiting participants),and the vaccines in ongoing phase III studies (still re-cruiting participants). These groups were further clas-sified according to the quality of the data currentlyavailable to review the efficacy and safety of each vac-cine. Priority was given to data obtained from studiespublished in peer-reviewed journals, followed by dataobtained from press release documents.Vaccine technologyFor each of the vaccines that reached phase III clinicaltrials, the technology used for the development of thevaccine was identified. These technologies fall into twocategories: protein-based vaccines, used to inject par-ticipants with SARS-CoV-2 proteins; and gene-basedvaccines, used to inject participants with SARS-CoV-2genetic material.Vaccine phase III clinical trial dataThe data from phase III clinical trials were summarizedfor vaccines with data available from peer-reviewedpublications and vaccines with only press-releaseddata. The vaccines were ordered according to the num-ber of COVID-19 cases used to calculate their efficacy,prioritizing studies with a greater number of COVID-19 cases. We also evaluated the generalizability of theirrespective study data, as determined by the number ofstudy subjects and the number of countries participat-ing in the trial.Vaccine safety dataData concerning the safety of the vaccines were ob-tained from peer-reviewed publications as well as pressrelease documents.Vaccine efficacy and SARS-CoV-2 variantsA review of peer-reviewed publications was performedto evaluate vaccine efficacy in relation to emergentULJRI | https://ir.library.louisville.edu/jri/vol5/iss1/2 1ULJRI An Update on the Leading COVID-19 VaccinesFigure 1. Vaccines that reached phase III of clinical development.Figure 2. Phase III vaccines categorized by technology.ULJRI | https://ir.library.louisville.edu/jri/vol5/iss1/2 2ULJRI An Update on the Leading COVID-19 VaccinesSARS-CoV-2 variants.ResultsVaccines that reached phase III of clinical developmentWe identified 10 vaccines that reached phase III of clini-cal development. The classification of these 10 vaccinesvaccines according to phase III clinical trial status—completed or ongoing—and availability of clinical trialdata are depicted in Figure 1.Vaccine TechnologyThe technology used in the development of these 10vaccines is depicted in Figure 2. Four vaccines used aprotein-based technology, and six vaccines used gene-based technology.Vaccine phase III clinical trial dataFour vaccines have completed phase III clinical trialswith data available in peer-reviewed journals. Our re-view of the data from these clinical trials in relationto vaccine efficacy, number of trial participants, num-ber of cases of COVID-19, and location of trial sites isdescribed in Table 1.[2–7] We identified three vaccineswith phase III clinical trial data from press release doc-uments. The review of the available data for these vac-cines is described in Table 2.[8–12]Vaccine safety dataSome recipients of the vaccines under discussion havereported mild to moderate adverse events. Local ad-verse events include pain at injection site, erythema,pruritus and lymphadenopathy. Systemic adverseevents include fatigue, headache, fever, chills, nau-sea and vomiting. The Pfizer vaccine was associ-ated with four cases of severe adverse events, includ-ing shoulder injury related to vaccine administration,right axillary lymphadenopathy, paroxysmal ventric-ular arrhythmia, and right leg paresthesia.[3] Initially,three cases of transverse myelitis (TM) and one case ofmultiple sclerosis (MS) were associated with Oxford-AstraZeneca vaccine, in response to which, the studywas placed on temporary hold for careful independentreview of each case.[4] It was determined that only 1case of TM in the vaccine group was a vaccine-relatedadverse event, while the remaining 2 cases of TM—onein the vaccine group, the other in placebo group—wereunrelated to the vaccine.[4] Further independent inves-tigation revealed that the patient in the vaccine groupwho developed MS 10 days after receiving the first dosehad pre-existing, underlying, unrecognized MS; thus,this case was also found to be unrelated to the vac-cine.[4]Pfizer/BioNTech reported six deaths during theirstudy, two from the vaccine group and four from theplacebo group. However, the investigators concludedthat these deaths were not related to the vaccine or tothe placebo.[3] Gamaleya investigators reported threedeaths during the study, but none of these was reportedto be associated with the vaccine.[7] Johnson & Johnsonalso reported three deaths that were not related to thestudy.[8] Oxford-AstraZeneca reported five deaths, onein the vaccine group and four in the placebo group.[4]The death in the vaccine group was deemed unrelatedto the vaccine or to COVID-19, while in the placebogroup, there was one death due to severe COVID-19leading to hospitalization 21 days after the first placebodose. The remaining three deaths in the placebo groupwere unrelated to COVID-19 or to the vaccine.[4]Vaccine efficacy and SARS-CoV-2 variantsData on the potential efficacy of four vaccines againstnew SARS-CoV-2 variants, as well as the origins of thevariants and the locations of their mutations, are de-scribed in Table 3.[8–10, 13–17] There are currently noavailable data on the impact of the new COVID-19 vari-ants on the severity of the disease, but the UK vari-ant (B.1.1.7) and Brazil variant (P.1) have been foundto be more transmissible than the original SARS-CoV-2 virus.[13] In a recent study, the Pfizer/BioNTechvaccine demonstrated poor efficacy against the SouthAfrica variant (B.1.351).[18]DiscussionHere, we reviewed the available data on the 10 vac-cines that have—as of March 1, 2021—reached phaseIII of the clinical development process. Data from peer-reviewed publications are available for only four vac-cines. The existing evidence concerning vaccine effi-cacy and safety is encouraging, but we still do not havedata on vaccine effectiveness and possible long-termcomplications. As more vaccines come into the mar-ket, it will be important to define which vaccines willbe the most effective in preventing COVID-19, as wellas achieving herd immunity.The existing data on vaccine efficacy against the emerg-ing SARS-CoV-2 variants are very limited. Only fourvaccines (Pfizer/BioNTech, Novavax, Johnson & John-son, and Bharat Biotech) have demonstrated efficacyagainst these variants; in the cases of Pfizer/BioNTechand Novavax, these effects have only been documentedin vitro. No data are available on the efficacy of anyvaccine against the California variant (CAL.20C). Fu-ture research should appraise COVID-19 vaccines onthe basis of variant coverage. With an increasinglybroad range of vaccines available, the potential risksand benefits of combining different vaccines also re-quire study.ULJRI | https://ir.library.louisville.edu/jri/vol5/iss1/2 3ULJRI An Update on the Leading COVID-19 VaccinesTable 1. Vaccines with peer-reviewed data.Vaccine Type Participants COVID-19Cases Efficacy (95% CI) Phase III Trial SiteNo. of doses(days apart)Enrolled Vaccine PlaceboMod-NIH RNA 30,420 15,210 15,210 196 94.1 (89.3–96.8) USA 2 (28)Pfi-BNT RNA 43,448 21,720 21,728 170 94.6 (89.9–97.3) USA, Germany, Turkey, SouthAfrica, Brazil, Argentina2 (21)Oxf-Ast Viral vector 23,848 12,082 11,766 131 70.4 (54.8–80.6) UK, South Africa, Brazil 2 (28)Gamaleya Viral vector 21,977 16,501 5,476 78 91.6 (85.6–95.2) Russia 2 (21)MOD-NIH: mRNA-1273, developed by Moderna and the National Institutes of Health.[2]Pfi-BNT: BNT162b2, developed by Pfizer and BioNTech.[3]Oxf-Ast: Covishield/ChAdOx1 nCoV-19 (AZD1222), developed by Oxford University and AstraZeneca.[4, 5]Gamaleya: Sputnik V/Gam-COVID-Vac, developed by the Gamaleya Research Institute.[6, 7]Table 2. Vaccines with press release data.Vaccine Type Participants COVID-19Cases Efficacy (95% CI) Phase III Trial Site No. of dosesEnrolled Vaccine PlaceboJ & J Viral vector 44,325 19,866 NA 469 66% (NA) USA, Argentina,Brazil, Chile,Colombia, Mexico,Peru, South Africa1Nov-HHS Recombinant spikeprotein nanoparticle15,000 NA NA 62 (6:56)† 89.3% (75.2–95.4) UK24,400∗ NA NA 44 (15:29)† 60% (19.9–80.1) South Africa16,000 NA NA NA NA USA, MexicoBB-NIV Whole-virion inactivated 25,800 NA NA NA NA India 2J & J: Ad26.COV2-S, developed by Johnson & Johnson.[8, 9]Nov-HHS: NVX-CoV2373, developed by Novavax and the Department of Health and Human Services.[10–11]BB-NIV: Covaxin/BBV152, developed by Bharat Biotech and the National Institute of Virology.[12]∗Phase 2b. †Total (vaccine:placebo)Table 3. SARS-CoV-2 variants.Name Origin Location of Mutations First Reported First Reported (US) Vaccine EffectivenessB.1.1.7 [13] UK Mutation in RBD* of spikeprotein at position 501:amino acid asparagine (N)replaced with tyrosine (Y).†P618H replacement on thespike proteins.Deletion at positions 69 and70 of spike protein.UK, September 2020 December 2020 Pfizer/BioNTech (in vitrostudies) [14]Novavax (NVX-CoV2373)89.3% efficacy [10]Covaxin/BBV152 BharatBiotech (in vitro studies) [15]B.1.351 [13] South Africa Eight lineage-defining muta-tions in the spike proteinSpike protein, includingK417N, E484K, N501YSouth Africa, October 2020 January 2021 Pfizer/BioNTech (in vitrostudies) [14]Janssen (Phase III trial, 95%S.A. population) [8, 9]Novavax (NVX-CoV2373)60% efficacy [10]Moderna (mRNA-1273) [17]P.1 [13] Brazil 17 unique mutations, includ-ing 3 in RBD of spike proteinJapan, January 2021 January 2021 Janssen [8, 9]Novavax (NVX-CoV2373)[10]CAL.20C [16] USA (Southern CA) Cluster 20C consists of 5mutations: ORF1a: I4205V,ORF1b: D1183Y, S: S13I;W152C; L452R (S13I andW152C in the N-terminal do-main, and L452R in RBD)Los Angeles (CA), July 2020 July 2020 Unknown∗Receptor binding domain †The shorthand for this mutation is N501YULJRI | https://ir.library.louisville.edu/jri/vol5/iss1/2 4ULJRI An Update on the Leading COVID-19 VaccinesReceived: March 3, 2021Accepted: March 3, 2021Published: March 3, 2021Copyright: © 2021 The author(s). This original article isbrought to you for free and open access by ThinkIR: The Uni-versity of Louisville’s Institutional Repository. For more infor-mation, please contact thinkir@louisville.edu. This article isdistributed under the terms of the Creative Commons Attribu-tion 4.0 International License (CC BY 4.0), which permits un-restricted use, distribution, and reproduction in any medium,provided the original author and source are credited.Funding Source: The author(s) received no specific fundingfor this study.Conflict of Interest: All authors declared no conflict of inter-est in relation to the main objective of this work.References1. Draft landscape and tracker of COVID-19 candidate vac-cines. 2021. Available at: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. Ac-cessed 15 February 2021.2. Baden LR, El Sahly HM, Essink B, et al. Efficacy andsafety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl JMed 2020; 384:403–416. doi: 10.1056/NEJMoa2035389.PMID: 33378609.3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and effi-cacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl JMed 2020; 383:2603–2615. doi: 10.1056/NEJMoa2034577.PMID: 33301246.4. Voysey M, Clemens SAC, Madhi SA, et al. Safety and ef-ficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) againstSARS-CoV-2: An interim analysis of four randomised con-trolled trials in Brazil, South Africa, and the UK. Lancet 2021;397:99–111.5. Voysey M, Costa Clemens SA, Madhi SA, et al. Singledose administration, and the influence of the timing of thebooster dose on immunogenicity and efficacy of ChAdOx1nCoV-19 (AZD1222) vaccine. SSRN [Preprint]. 2021 doi:10.2139/ssrn.3777268.6. Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safetyand efficacy of an rAd26 and rAd5 vector-based heterolo-gous prime-boost COVID-19 vaccine: an interim analysis of arandomised controlled phase 3 trial in Russia. Lancet 2021;397:671–681. doi: 10.1016/S0140-6736(21)00234-8. PMID:33545094.7. Jones I, Roy P. Sputnik V COVID-19 vaccine candidateappears safe and effective. Lancet 2021; 397:642–643. doi:10.1016/S0140-6736(21)00191-4. PMID: 33545098.8. Johnson & Johnson Announces Single-Shot JanssenCOVID-19 Vaccine Candidate Met Primary Endpoints inInterim Analysis of its Phase 3 ENSEMBLE Trial. 2021.Available at: https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic. Ac-cessed 15 February 2021.9. Janssen Investigational COVID-19 Vaccine: InterimAnalysis of Phase 3 Clinical Data Released. Availableat: https://www.nih.gov/news-events/news-releases/janssen-investigational-covid-19-vaccine-interim-analysis-phase-3-clinical-data-released. Accessed 15 February 2021.10. Novavax COVID-19 Vaccine Demonstrates 89.3% Ef-ficacy in UK Phase 3 Trial. 2021. Available at: https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3.Accessed 14 March 2021.11. Novavax Announces Start of Rolling Review by Mul-tiple Regulatory Authorities for COVID-19 Vaccine Autho-rization. 2021. Available at: https://ir.novavax.com/news-releases/news-release-details/novavax-announces-start-rolling-review-multiple-regulatory. Accessed 14 March 2021.12. COVAXIN®- India’s First Indigenous Covid-19 Vaccine.2021. Available at: https://www.bharatbiotech.com/covaxin.html. Accessed 15 February 2021.13. Science Brief: Emerging SARS-CoV-2 Variants.2021. Available at: https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html. Accessed 15 February 2021.14. Pfizer and BioNTech Publish Results of Study ShowingCOVID-19 Vaccine Elicits Antibodies that Neutralize Pseu-dovirus Bearing the SARS-CoV-2 U.K. Strain Spike Proteinin Cell Culture. 2021. Available at: https://www.pfizer.com/.Accessed 15 February 2021.15. Sapkal GN, Yadav PD, Ella R, et al. Neutraliza-tion of UK-variant VUI-202012/01 with COVAXIN vacci-nated human serum. bioRxiv [Preprint]. 2021 doi:10.1101/2021.01.26.426986.16. Zhang W, Davis BD, Chen SS, Sincuir Martinez JM,Plummer JT, Vail E. Emergence of a novel SARS-CoV-2 vari-ant in southern California. JAMA 2021. Online ahead of print.doi: 10.1001/jama.2021.1612.17. Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccineinduces neutralizing antibodies against spike mutants fromglobal SARS-CoV-2 variants. bioRxiv [Preprint]. 2021 doi:10.1101/2021.01.25.427948. PMID: 33501442.18. Liu Y, Liu J, Xia H, et al. Neutralizing activity ofBNT162b2-elicited serum—preliminary report. N Engl J Med2021. Online ahead of print. doi: 10.1056/NEJMc2102017.ULJRI | https://ir.library.louisville.edu/jri/vol5/iss1/2 5

An Update on the Leading COVID-19 Vaccines

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An Update on the Leading COVID-19 Vaccines

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