PURPOSE OF REVIEW: Antisevere acute respiratory syndrome-corona virus 2 (SARS-CoV-2) vaccines may provide prompt, effective, and safe solution for the COVID-19 pandemic. Several vaccine candidates have been evaluated in randomized clinical trials (RCTs). Furthermore, data from observational studies mimicking real-life practice and studies on specific groups, such as pregnant women or immunocompromised patients who were excluded from RCTs, are currently available. The main aim of the review is to summarize and provide an immunologist's view on mechanism of action, efficacy and safety, and future challenges in vaccination against SARS-CoV-2. RECENT FINDINGS: mRNA and recombinant viral vector-based vaccines have been approved for conditional use in Europe and the USA. They show robust humoral and cellular responses, high with efficacy in prevention of COVID-19 infection (66.9 95%) and favorable safety profile in RCTs. High efficacy of 80-92% was observed in real-life practice. A pilot study also confirmed good safety profile of the mRNA vaccines in pregnant women. Unlike in those with secondary immunodeficiencies where postvaccination responses did not occur, encouraging results were obtained in patients with inborn errors of immunity. SUMMARY: Although both RCTs and observational studies suggest good efficacy and safety profiles of the vaccines, their long-term efficacy and safety are still being discussed. Despite the promising results, clinical evidence for specific groups such as children, pregnant and breastfeeding women, and immunocompromised patients, and for novel virus variants are lacking. VIDEO ABSTRACT: http://links.lww.com/COAI/A21.

Department of Immunology 2nd Faculty of Medicine Charles University

Department of Pediatric and Adult Rheumatology Motol University Hospital Prague Czech Republic

Zobrazit více v PubMed

Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17:181–192.

Wit E de, van Doremalen N, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016; 14:523–534.

European Centre for Disease Prevention and Control. COVID-19 situation update for the EU/EEA. 2-Jul-2021. www.ecdc.europa.eu/en/cases-2019-ncov-eueea (accessed 5 July 2021).

Centres for Disease Control and Prevention. Covid Data Tracker. 2-Jul-2021. https://covid.cdc.gov/covid-data-tracker/#datatracker-home (accessed 5 July 2021).

World Health Organization. WHO Coronavirus (COVID-19) Dashboard. 1-Jul-2021. https://covid19.who.int/ (accessed 5 July 2021).

Da Rosa Mesquita R, Francelino Silva Junior LC, Santos Santana FM, et al. Clinical manifestations of COVID-19 in the general population: systematic review. Wien Klin Wochenschr 2021; 133:377–382.

Jin J-M, Bai P, He W, et al. Gender differences in patients with COVID-19: focus on severity and mortality. Front Public Health 2020; 8:152.

Abrams JY, Oster ME, Godfred-Cato SE, et al. Factors linked to severe outcomes in multisystem inflammatory syndrome in children (MIS-C) in the USA: a retrospective surveillance study. Lancet Child Adolesc Health 2021; 5:323–331.

Lotfi M, Hamblin MR, Rezaei N. COVID-19: transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta 2020; 508:254–266.

Pak A, Adegboye OA, Adekunle AI, et al. Economic consequences of the COVID-19 outbreak: the need for epidemic preparedness. Front Public Health 2020; 8:241.

Zuo J, Dowell AC, Pearce H, et al. Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection. Nat Immunol 2021; 22:620–626.

Cromer D, Juno JA, Khoury D, et al. Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection. Nat Rev Immunol 2021; 21:395–404.

Hall VJ, Foulkes S, Charlett A, et al. SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN). Lancet 2021; 397:1459–1469.

Hansen CH, Michlmayr D, Gubbels SM, et al. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. Lancet 2021; 397:1204–1212.

Sanyang B, Kanteh A, Usuf E, et al. COVID-19 reinfections in The Gambia by phylogenetically distinct SARS-CoV-2 variants-first two confirmed events in west Africa. Lancet Glob Health 2021; 9:e905–e907.

Tregoning JS, Brown ES, Cheeseman HM, et al. Vaccines for COVID-19. Clin Exp Immunol 2020; 202:162–192.

Strizova Z, Smetanova J, Bartunkova J, Milota T. Principles and challenges in anti-COVID-19 vaccine development. Int Arch Allergy Immunol 2021; 182:339–349.

Yang Y, Du L. SARS-CoV-2 spike protein: a key target for eliciting persistent neutralizing antibodies. Signal Transduct Target Ther 2021; 6:95.

European Medicines Agency. COVID-19 vaccines. https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/covid-19-vaccines (accessed 5 July 2021).

U.S. Food and Drug Administration. COVID-19 Vaccines. 2-Jul-2021. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines (accessed 5 July 2021).

European Centre for Disease Prevention and Control. COVID-19 Vaccine Tracker. 5-Jul-2021. https://vaccinetracker.ecdc.europa.eu/public/extensions/COVID-19/vaccine-tracker.html#uptake-tab (accessed 5 July 2021).

Zhang C, Maruggi G, Shan H, Li J. Advances in mRNA vaccines for infectious diseases. Front Immunol 2019; 10:594.

Ross J. mRNA stability in mammalian cells. Microbiol Rev 1995; 59:423–450.

Fausther-Bovendo H, Kobinger GP. Preexisting immunity against Ad vectors: humoral, cellular, and innate response, what's important? Hum Vaccin Immunother 2014; 10:2875–2884.

Humphreys IR, Sebastian S. Novel viral vectors in infectious diseases. Immunology 2018; 153:1–9.

Rauch S, Jasny E, Schmidt KE, Petsch B. New vaccine technologies to combat outbreak situations. Front Immunol 2018; 9:1963.

Teijaro JR, Farber DL. COVID-19 vaccines: modes of immune activation and future challenges. Nat Rev Immunol 2021; 21:195–197.

Mulligan MJ, Lyke KE, Kitchin N, et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 2020; 586:589–593.

Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med 2020; 383:2427–2438.

Ewer KJ, Barrett JR, Belij-Rammerstorfer S, et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med 2021; 27:270–278.

Folegatti PM, Ewer KJ, Aley PK, 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. 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.

Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 2020; 586:594–599.

Stephenson KE, Le Gars M, Sadoff J, et al. Immunogenicity of the Ad26.COV2.S vaccine for COVID-19. JAMA 2021; 325:1535–1544.

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.

Sandmann FG, Davies NG, Vassall A, et al. The potential health and economic value of SARS-CoV-2 vaccination alongside physical distancing in the UK: a transmission model-based future scenario analysis and economic evaluation. Lancet Infect Dis 2021; 21:962–974.

Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383:2603–2615.

Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384:403–416.

Voysey M, Clemens SAC, 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; 397:99–111.

Sadoff J, Gray G, Vandebosch A, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med 2021; 384:2187–2201.

Ledford H. Six months of COVID vaccines: what 1.7 billion doses have taught scientists. Nature 2021; 594:164–167.

Dagan N, Barda N, Kepten E, et al. BNT162b2 mRNA Covid-19 vaccine in a nationwide mass vaccination setting. N Engl J Med 2021; 384:1412–1423.

Pritchard E, Matthews PC, Stoesser N, et al. Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom. Nat Med 2021; 27:1370–1378.

Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study. BMJ 2021; 373:n1088.

Li X, Ostropolets A, Makadia R, et al. Characterizing the incidence of adverse events of special interest for COVID-19 vaccines across eight countries: a multinational network cohort study. medRxiv 2021.

Cines DB, Bussel JB. SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. N Engl J Med 2021; 384:2254–2256.

Centers for Disease Control and Prevention. Variants of concern. 29-Jun-2021. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html (accessed 5 July 2021).

European Centre for Disease Prevention and Control. Variants of concern. 1-Jul-2021. https://www.ecdc.europa.eu/en/covid-19/variants-concern (accessed 5 July 2021).

Abdool Karim SS, Oliveira T de. New SARS-CoV-2 variants - clinical, public health, and vaccine implications. N Engl J Med 2021; 384:1866–1868.

Bian L, Gao F, Zhang J, et al. Effects of SARS-CoV-2 variants on vaccine efficacy and response strategies. Expert Rev Vaccines 2021; 20:365–373.

Karim SSA. Vaccines and SARS-CoV-2 variants: the urgent need for a correlate of protection. Lancet 2021; 397:1263–1264.

Noh JY, Jeong HW, Shin E-C. SARS-CoV-2 mutations, vaccines, and immunity: implication of variants of concern. Signal Transduct Target Ther 2021; 6:203.

Vojdani A, Kharrazian D. Potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases. Clin Immunol 2020; 217:108480.

Talotta R. Do COVID-19 RNA-based vaccines put at risk of immune-mediated diseases? In reply to ‘potential antigenic cross-reactivity between SARS-CoV-2 and human tissue with a possible link to an increase in autoimmune diseases’. Clin Immunol 2021; 224:108665.

Subbaraman N. Pregnancy and COVID: what the data say. Nature 2021; 591:193–195.

Shimabukuro TT, Kim SY, Myers TR, et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N Engl J Med 2021; 384:2273–2282.

Meyts I, Bucciol G, Quinti I, et al. Coronavirus disease 2019 in patients with inborn errors of immunity: an international study. J Allergy Clin Immunol 2021; 147:520–531.

Sobh A, Bonilla FA. Vaccination in primary immunodeficiency disorders. J Allergy Clin Immunol Pract 2016; 4:1066–1075.

Bonilla FA. Update: vaccines in primary immunodeficiency. J Allergy Clin Immunol 2018; 141:474–481.

Hagin D, Freund T, Navon M, et al. Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity. J Allergy Clin Immunol 2021; 148:739–749.

Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA 2021; 325:2204–2206.

Peled Y, Ram E, Lavee J, et al. BNT162b2 vaccination in heart transplant recipients: clinical experience and antibody response. J Heart Lung Transplant 2021; 40:759–762.

Spiera R, Jinich S, Jannat-Khah D. Rituximab, but not other antirheumatic therapies, is associated with impaired serological response to SARS- CoV-2 vaccination in patients with rheumatic diseases. Ann Rheum Dis 2021; 80:1357–1359.

Prendecki M, Clarke C, Edwards H, et al. Humoral and T-cell responses to SARS-CoV-2 vaccination in patients receiving immunosuppression. Ann Rheum Dis 2021; 80:1322–1329.

Wang M-Y, Zhao R, Gao L-J, et al. SARS-CoV-2: structure, biology, and structure-based therapeutics development. Front Cell Infect Microbiol 2020; 10:587269.

BMC. ISRCTN Registry. 2-Jul-2021. https://www.isrctn.com/ (accessed 5 July 2021).

U.S. National Library of Medicine. ClinicalTrials. https://clinicaltrials.gov/ (accessed 5 July 2021)

Clinical Outcome of Coronavirus Disease 2019 in Patients with Primary Antibody Deficiencies

SARS-CoV-2-specific humoral and cellular immune responses to BNT162b2 vaccine in Fibrodysplasia ossificans progressiva patients