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Immunogenicity and Safety of the COVID-19 Vaccines Compared With Control in Healthy Adults: A Qualitative and Systematic Review

Published:October 14, 2021DOI:https://doi.org/10.1016/j.jval.2021.09.003

      Highlights

      • COVID-19 vaccines are currently used on the basis of immunogenicity and safety profiles data. This study provides a comprehensive and up-to-date qualitative review of the COVID-19 vaccine data in the literature.
      • Adverse events and immunogenicity profiles in COVID-19 vaccines were similar between younger (18-59 years old) and older (60 years and older) adults.

      Abstract

      Objectives

      Emergence of severe acute respiratory syndrome coronavirus 2 infections and the resultant disease, COVID-19 led the world into 238 million cases and 4.8 million deaths over the first 22 months of the pandemic. While numerous vaccines have been developed to combat this pandemic, limited literature is available regarding the comparison of these vaccines. This study aims to systematically review and evaluate the immunogenicity and safety of COVID-19 vaccines compared with control arms in the healthy adult population.

      Methods

      A literature search was conducted in PubMed, MEDLINE, Embase, and Cochrane up to July 4, 2021. Randomized controlled trials assessing the immunogenicity of any dose of COVID-19 vaccine in adults by anti–severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies geometric mean titers (GMTs) and neutralizing antibodies GMT response at 28 days postimmunization compared with the control groups in the healthy adults were considered for inclusion. Groups at day 28 with the highest GMT were further examined for their adverse events.

      Results

      Of the 341 citations retrieved, 19 were included. This covered a total of 16 vaccines involving 8342 subjects aged between 30.8 and 69.7 years, comprising 52.13% females. All studies reported GMT at or close to 28 days postvaccination compared with placebo and comparator, and 13 of 19 studies reported seroconversion rates. While 15 of 16 vaccines reported adverse events that ranged from mild to severe, 1 of 16 (AD26.COV2.S) noted 1 case of a vaccine-related serious adverse event—high fever 6 hours after vaccination. Local reactions (such as redness, pain, and swelling) and systematic reactions (such as fatigue, fever, and headache) were commonly noted. Safety between vaccines was similar; however, higher rates of severe adverse events were noted in Ad5-vectored COVID-19, AD26.COV2.S, ChAdOx nCoV-19, and mRNA-1273. No all-cause mortality was documented in any vaccines.

      Conclusions

      All 16 vaccines elicited an immune response substantially higher than the control groups while maintaining tolerable safety profiles.

      Keywords

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      References

        • Dong E.
        • Du H.
        • Gardner L.
        An interactive web-based dashboard to track COVID-19 in real time [published correction appears in Lancet Infect Dis. 2020;20(9):e215].
        Lancet Infect Dis. 2020; 20: 533-534
      1. WHO Director-General’s opening remarks at the media briefing on COVID-19 – 11 March 2020. World Health Organization.
        • Comas-Herrera A.
        • Zalakaín J.
        • Lemmon E.
        • et al.
        Mortality associated with COVID-19 outbreaks in care homes mortality associated with COVID-19 in care homes: international evidence. International Long-Term Care Policy Network.
        • Bonanad C.
        • García-Blas S.
        • Tarazona-Santabalbina F.
        • et al.
        The effect of age on mortality in patients with COVID-19: A meta-analysis with 611,583 Subjects.
        J Am Med Dir Assoc. 2020; 21: 915-918
        • Gold M.S.
        • Sehayek D.
        • Gabrielli S.
        • Zhang X.
        • McCusker C.
        • Ben-Shoshan M.
        COVID-19 and comorbidities: a systematic review and meta-analysis.
        Postgrad Med. 2020; 132: 749-755
        • Alimohamadi Y.
        • Sepandi M.
        • Taghdir M.
        • Hosamirudsari H.
        Determine the most common clinical symptoms in COVID-19 patients: a systematic review and meta-analysis.
        J Prev Med Hyg. 2020; 61: E304-E312
        • Wang Z.
        • Deng H.
        • Ou C.
        • et al.
        Clinical symptoms, comorbidities and complications in severe and non-severe patients with COVID-19: a systematic review and meta-analysis without cases duplication.
        Med (Baltimore). 2020; 99e23327
        • Kronbichler A.
        • Kresse D.
        • Yoon S.
        • Lee K.H.
        • Effenberger M.
        • Shin J.I.
        Asymptomatic patients as a source of COVID-19 infections: a systematic review and meta-analysis.
        Int J Infect Dis. 2020; 98: 180-186
      2. Qian M, Jiang J. COVID-19 and social distancing [published online May 25, 2020]. J Public Health (Bangkok). https://doi.org/10.1007/s10389-020-01321-z.

        • Wang Q.
        • Yu C.
        The role of masks and respirator protection against SARS-CoV-2.
        Infect Control Hosp Epidemiol. 2020; 41: 746-747
        • Hossein-khannazer N.
        • Shokoohian B.
        • Shpichka A.
        • Aghdaei H.A.
        • Timashev P.
        • Vosough M.
        An update to novel therapeutic approaches for treatment of COVID-19.
        J Mol Med (Berl). 2021; 99: 303-310
        • Craven J.
        COVID-19 vaccine tracker. Regulatory Affairs Professional Society.
        • Polack F.P.
        • Thomas S.J.
        • Kitchin N.
        • et al.
        Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.
        N Engl J Med. 2020; 383: 2603-2615
        • Baden L.R.
        • El Sahly H.M.
        • Essink B.
        • et al.
        Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.
        N Engl J Med. 2021; 384: 403-416
      3. Yuan P, Ai P, Liu Y, et al. Safety, tolerability, and immunogenicity of COVID-19 vaccines: a systematic review and meta-analysis. Preprint. Posted online November 4, 2020. medRxiv 2020.11.03.20224998. https://doi.org/10.1101/2020.11.03.20224998.

        • Pormohammad A.
        • Zarei M.
        • Ghorbani S.
        • et al.
        Efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis of randomized clinical trials.
        Vaccines (Basel). 2021; 9: 467
        • Xing K.
        • Tu X.Y.
        • Liu M.
        • et al.
        Efficacy and safety of COVID-19 vaccines: a systematic review.
        Zhongguo Dang Dai Er Ke Za Zhi. 2021; 23: 221-228
        • Hodgson S.H.
        • Mansatta K.
        • Mallett G.
        • Harris V.
        • Emary K.R.W.
        • Pollard A.J.
        What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2.
        Lancet Infect Dis. 2021; 21: e26-e35
        • Page M.J.
        • McKenzie J.E.
        • Bossuyt P.M.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • Sterne J.A.C.
        • Savović J.
        • Page M.J.
        • et al.
        RoB 2: a revised tool for assessing risk of bias in randomised trials.
        BMJ. 2019; 366: l4898
        • Brochot E.
        • Demey B.
        • Touzé A.
        • et al.
        Anti-spike, anti-nucleocapsid and neutralizing antibodies in SARS-CoV-2 inpatients and asymptomatic individuals.
        Front Microbiol. 2020; 11584251
        • Yu X.
        • Gilbert P.B.
        • Hioe C.E.
        • Zolla-Pazner S.
        • Self S.G.
        Statistical approaches to analyzing HIV-1 neutralizing antibody assay data.
        Stat Biopharm Res. 2012; 4: 1-13
      4. Guidelines on Clinical Evaluation of Vaccines: Regulatory Expectations. World Health Organization.
        • Wan X.
        • Wang W.
        • Liu J.
        • Tong T.
        Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.
        BMC Med Res Methodol. 2014; 14: 135
        • Chu L.
        • Mcphee R.
        • Huang W.
        • et al.
        A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine.
        Vaccine. 2021; 39: 2791-2799
        • Ella R.
        • Vadrevu K.M.
        • Jogdand H.
        • et al.
        Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial [published correction appears in Lancet Infect Dis. 2021;21(4):e81].
        Lancet Infect Dis. 2021; 21: 637-646
        • Walsh E.E.
        • Frenck Jr., R.W.
        • Falsey A.R.
        • et al.
        Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates.
        N Engl J Med. 2020; 383: 2439-2450
        • Wu Z.
        • Hu Y.
        • Xu M.
        • et al.
        Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.
        Lancet Infect Dis. 2021; 21: 803-812
        • Xia S.
        • Zhang Y.
        • Wang Y.
        • et al.
        Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial.
        Lancet Infect Dis. 2021; 21: 39-51
        • Xia S.
        • Duan K.
        • Zhang Y.
        • et al.
        Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials.
        JAMA. 2020; 324: 951-960
        • Yang S.
        • Li Y.
        • Dai L.
        • et al.
        Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.
        Lancet Infect Dis. 2021; 21: 1107-1119
        • Zhang Y.
        • Zeng G.
        • Pan H.
        • et al.
        Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.
        Lancet Infect Dis. 2021; 21: 181-192
        • Zhu F.C.
        • Guan X.H.
        • Li Y.H.
        • et al.
        Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.
        Lancet. 2020; 396: 479-488
        • Pan H.X.
        • Liu J.K.
        • Huang B.Y.
        • et al.
        Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials.
        Chin Med J (Engl). 2021; 134: 1289-1298
        • Ward B.J.
        • Gobeil P.
        • Séguin A.
        • et al.
        Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19.
        Nat Med. 2021; 27: 1071-1078
        • Folegatti P.M.
        • Ewer K.J.
        • Aley P.K.
        • et al.
        Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial [published correction appears in Lancet. 2020;396(10249):466] [published correction appears in Lancet. 2020;396(10266):1884].
        Lancet. 2020; 396: 467-478
        • Keech C.
        • Albert G.
        • Cho I.
        • et al.
        Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine.
        N Engl J Med. 2020; 383: 2320-2332
        • Li J.
        • Hui A.
        • Zhang X.
        • et al.
        Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study.
        Nat Med. 2021; 27: 1062-1070
        • Mulligan M.J.
        • Lyke K.E.
        • Kitchin N.
        • et al.
        Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults [published correction appears in Nature. 2021;590(7844):E26].
        Nature. 2020; 586: 589-593
        • Pu J.
        • Yu Q.
        • Yin Z.
        • et al.
        The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18-59 years: a phase I randomized, double-blinded, controlled trial.
        Vaccine. 2021; 39: 2746-2754
        • Ramasamy M.N.
        • Minassian A.M.
        • Ewer K.J.
        • et al.
        Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial [published correction appears in Lancet. 2021;396(10267):1978] [published correction appears in Lancet. 2021;397(10282):1350].
        Lancet. 2021; 396: 1979-1993
        • Richmond P.
        • Hatchuel L.
        • Dong M.
        • et al.
        Safety and immunogenicity of S-trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial.
        Lancet. 2021; 397: 682-694
        • Sadoff J.
        • Le Gars M.
        • Shukarev G.
        • et al.
        Interim Results of a Phase 1-2a Trial of Ad26.COV2.S COVID-19 Vaccine.
        N Engl J Med. 2021; 384: 1824-1835
      5. https://clinicaltrials.gov/ct2/about-site/link-to
        Date: 2019
        Date accessed: October 11, 2021
      6. https://www.chictr.org.cn/abouten.aspx
        Date: 2021
        Date accessed: October 11, 2021
      7. COVID-19 vaccine tracker and landscape. World Health Organization.
        • Gustafson C.E.
        • Kim C.
        • Weyand C.M.
        • Goronzy J.J.
        Influence of immune aging on vaccine responses.
        J Allergy Clin Immunol. 2020; 145: 1309-1321
        • Shen-Orr S.S.
        • Furman D.
        Variability in the immune system: of vaccine responses and immune states.
        Curr Opin Immunol. 2013; 25: 542-547
        • Saxena M.
        • Van T.T.H.
        • Baird F.J.
        • Coloe P.J.
        • Smooker P.M.
        Pre-existing immunity against vaccine vectors -- friend or foe?.
        Microbiology (Reading). 2013; 159: 1-11
        • Normark J.
        • Vikström L.
        • Gwon Y.D.
        • et al.
        Heterologous ChAdOx1 nCoV-19 and mRNA-1273 vaccination.
        N Engl J Med. 2021; 385: 1049-1051
        • Salje H.
        • Rodríguez-Barraquer I.
        • Rainwater-Lovett K.
        • et al.
        Variability in dengue titer estimates from plaque reduction neutralization tests poses a challenge to epidemiological studies and vaccine development.
        PLoS Negl Trop Dis. 2014; 8e2952
        • Faber J.
        • Fonseca L.M.
        How sample size influences research outcomes.
        Dental Press J Orthod. 2014; 19: 27-29
        • Jefferson T.
        • Rudin M.
        • Di Pietrantonj C.
        Adverse events after immunisation with aluminium-containing DTP vaccines: systematic review of the evidence.
        Lancet Infect Dis. 2004; 4: 84-90
        • Djurisic S.
        • Jakobsen J.C.
        • Petersen S.B.
        • Kenfelt M.
        • Gluud C.
        Aluminium adjuvants used in vaccines versus placebo or no intervention.
        Cochrane Database Syst Rev. 2017; 2017CD012805
        • Massarweh A.
        • Eliakim-Raz N.
        • Stemmer A.
        • et al.
        Evaluation of seropositivity following BNT162b2 messenger RNA vaccination for SARS-CoV-2 in patients undergoing treatment for cancer.
        JAMA Oncol. 2021; 7: 1133-1140
        • Cines D.B.
        • Bussel J.B.
        SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia [published correction appears in N Engl J Med. 2021;384(23):e92].
        N Engl J Med. 2021; 384: 2254-2256
      8. Montgomery J, Ryan M, Engler R, et al. Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military [published online June 29, 2021]. JAMA Cardiol. https://doi.org/10.1001/jamacardio.2021.2833.