{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:35:18Z","timestamp":1760229318296,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Nebraska-Lincoln, Office of Research and Economic Development","award":["1 T32 AI125207","R01-AI147109"],"award-info":[{"award-number":["1 T32 AI125207","R01-AI147109"]}]},{"name":"National Institutes of Health (NIH)","award":["1 T32 AI125207","R01-AI147109"],"award-info":[{"award-number":["1 T32 AI125207","R01-AI147109"]}]},{"name":"NIH, National Institute for Allergies and Infectious Diseases (NIAID)","award":["1 T32 AI125207","R01-AI147109"],"award-info":[{"award-number":["1 T32 AI125207","R01-AI147109"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2\u20134 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the utility of serotype-switching to enhance the protective immune responses seen with homologous prime-boosting strategies. Immunization with an H2 centralized consensus showed a wide breadth of antibody responses after vaccination, protection against challenge with a divergent human H2 strain, and significantly reduced viral load in the lungs after challenge. Further, serotype switching between two species C adenoviruses enhanced protective antibody titers after heterologous boosting. These data support the notion that an adenoviral-vectored H2 centralized consensus vaccine has the ability to provide broadly cross-reactive immune responses to protect against divergent strains of H2 influenza and prepare for a possible pandemic.<\/jats:p>","DOI":"10.3390\/vaccines10060926","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T06:31:59Z","timestamp":1655101919000},"page":"926","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection against H2 Influenza a Virus"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7532-2256","authenticated-orcid":false,"given":"Erika M.","family":"Petro-Turnquist","sequence":"first","affiliation":[{"name":"Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, 4240 Fair Street, Lincoln, NE 68504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brianna L.","family":"Bullard","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, 4240 Fair Street, Lincoln, NE 68504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3214-4220","authenticated-orcid":false,"given":"Matthew J.","family":"Pekarek","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, 4240 Fair Street, Lincoln, NE 68504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5029-0662","authenticated-orcid":false,"given":"Eric A.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, 4240 Fair Street, Lincoln, NE 68504, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1086\/515616","article-title":"Pandemic versus Epidemic Influenza Mortality: A Pattern of Changing Age Distribution","volume":"178","author":"Simonsen","year":"1998","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.virol.2004.06.009","article-title":"Genetic analysis of human H2N2 and early H3N2 influenza viruses, 1957\u20131972: Evidence for genetic divergence and multiple reassortment events","volume":"328","author":"Lindstrom","year":"2004","journal-title":"Virology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1093\/infdis\/jiy291","article-title":"Population Serologic Immunity to Human and Avian H2N2 Viruses in the United States and Hong Kong for Pandemic Risk Assessment","volume":"218","author":"Babu","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4173","DOI":"10.1016\/j.vaccine.2021.05.064","article-title":"Seasonal influenza vaccination does not effectively expand H2 cross-reactive antibodies in humans","volume":"39","author":"Reneer","year":"2021","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Munster, V.J., Baas, C., Lexmond, P., Waldenstrom, J., Wallensten, A., Fransson, T., Rimmelzwaan, G.F., Beyer, W.E., Schutten, M., and Olsen, B. (2007). Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030061"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s11262-016-1368-0","article-title":"Genetic and molecular characterization of a novel reassortant H2N8 subtype avian influenza virus isolated from a domestic duck in Zhejiang Province in China","volume":"52","author":"Wu","year":"2016","journal-title":"Virus Genes"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7588","DOI":"10.1038\/srep07588","article-title":"Characterization of a Novel Reassortant Influenza A Virus (H2N2) from a Domestic Duck in Eastern China","volume":"4","author":"Ma","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_8","first-page":"386","article-title":"The preparedness plan for influenza pandemic","volume":"38","author":"Lee","year":"2005","journal-title":"J. Prev. Med. Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6367","DOI":"10.1016\/j.vaccine.2006.07.021","article-title":"A global pandemic influenza vaccine action plan","volume":"24","author":"Kieny","year":"2006","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e01907-18","DOI":"10.1128\/JVI.01907-18","article-title":"The Molecular Basis for Antigenic Drift of Human A\/H2N2 Influenza Viruses","volume":"93","author":"Linster","year":"2019","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1016\/j.vaccine.2017.01.026","article-title":"Evaluation of multivalent H2 influenza pandemic vaccines in mice","volume":"35","author":"Lenny","year":"2017","journal-title":"Vaccine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1128\/JVI.01829-13","article-title":"Evaluation of Three Live Attenuated H2 Pandemic Influenza Vaccine Candidates in Mice and Ferrets","volume":"88","author":"Chen","year":"2014","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1080\/21645515.2015.1010859","article-title":"H2N2 live attenuated influenza vaccine is safe and immunogenic for healthy adult volunteers","volume":"11","author":"Stukova","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.virol.2009.12.003","article-title":"Safety, immunogencity, and efficacy of a cold-adapted A\/Ann Arbor\/6\/60 (H2N2) vaccine in mice and ferrets","volume":"398","author":"Chen","year":"2010","journal-title":"Virology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1750-2659.2012.00350.x","article-title":"An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults","volume":"7","author":"Talaat","year":"2012","journal-title":"Influ. Other Respir. Viruses"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Weaver, E.A., Rubrum, A.M., Webby, R.J., and Barry, M.A. (2011). Protection against Divergent Influenza H1N1 Virus by a Centralized Influenza Hemagglutinin. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018314"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14912","DOI":"10.1038\/s41598-017-14891-y","article-title":"Efficacy of an Adenoviral Vectored Multivalent Centralized Influenza Vaccine","volume":"7","author":"Lingel","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nu\u00f1ez, I.A., Huang, Y., and Ross, T.M. (2021). Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections. Pathogens, 10.","DOI":"10.3390\/pathogens10111352"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1128\/CVI.05533-11","article-title":"Antibody Breadth and Protective Efficacy Are Increased by Vaccination with Computationally Optimized Hemagglutinin but Not with Polyvalent Hemagglutinin-Based H5N1 Virus-Like Particle Vaccines","volume":"19","author":"Giles","year":"2012","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1128\/JVI.03152-15","article-title":"Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses","volume":"90","author":"Carter","year":"2016","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/21645515.2017.1377376","article-title":"Immune responses after live attenuated influenza vaccination","volume":"14","author":"Mohn","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1016\/j.vaccine.2009.02.071","article-title":"Vaccine-derived poliovirus (VDPV): Impact on poliomyelitis eradication","volume":"27","author":"Minor","year":"2009","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3201\/eid1201.051147","article-title":"Vaccines for pandemic influenza","volume":"12","author":"Luke","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_24","unstructured":"WHO (2013). Live attenuated vaccines (LAV). Vaccine Safety Basics: E-learning Course, WHO."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1177\/1040638720907918","article-title":"Detection of live attenuated influenza vaccine virus and evidence of reassortment in the U.S. swine population","volume":"32","author":"Sharma","year":"2020","journal-title":"J. Vet. Diagn. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1038\/213612a0","article-title":"Adaptation and growth characteristics of influenza virus at 25 degrees c","volume":"213","author":"Maassab","year":"1967","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"728","DOI":"10.4049\/jimmunol.102.3.728","article-title":"Biologic and immunologic characteristics of cold-adapted influenza virus","volume":"102","author":"Maassab","year":"1969","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3389\/fimmu.2020.00909","article-title":"Factors Which Contribute to the Immunogenicity of Non-replicating Adenoviral Vectored Vaccines","volume":"11","author":"Coughlan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_29","unstructured":"(2022, April 11). Gene Therapy Clinical Trials (Wiley). Available online: https:\/\/a873679.fmphost.com\/fmi\/webd\/GTCT."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1517\/14712598.2010.519332","article-title":"Production of adenovirus vectors and their use as a delivery system for influenza vaccines","volume":"10","author":"Vemula","year":"2010","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0140-6736(20)31605-6","article-title":"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","volume":"396","author":"Zhu","year":"2020","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1056\/NEJMoa2105290","article-title":"Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) COVID-19 Vaccine","volume":"385","author":"Falsey","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"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","volume":"397","author":"Voysey","year":"2021","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa2034201","article-title":"Interim Results of a Phase 1-2a Trial of Ad26.COV2.S COVID-19 Vaccine","volume":"384","author":"Sadoff","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0140-6736(21)00234-8","article-title":"Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia","volume":"397","author":"Logunov","year":"2021","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1023\/A:1020555310558","article-title":"Development and improvement of a serum-free suspension process for the production of recombinant ade-noviral vectors using HEK293 cells","volume":"37","author":"Tsao","year":"2001","journal-title":"Cytotechnology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6745","DOI":"10.1128\/JVI.02484-05","article-title":"Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen","volume":"80","author":"Weaver","year":"2006","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.virol.2006.04.043","article-title":"A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses","volume":"353","author":"Liao","year":"2006","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.virol.2006.05.011","article-title":"Ancestral and consensus envelope immunogens for HIV-1 subtype C","volume":"352","author":"Kothe","year":"2006","journal-title":"Virology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Weaver, E.A., Nehete, P., Buchl, S.S., Senac, J.S., Palmer, D., Ng, P., Sastry, J., and Barry, M.A. (2009). Comparison of Replication-Competent, First Generation, and Helper-Dependent Adenoviral Vaccines. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005059"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1093\/infdis\/jir661","article-title":"Influenza Hemagglutination-Inhibition Antibody Titer as a Correlate of Vaccine-Induced Protection","volume":"204","author":"Ohmit","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17175","DOI":"10.1073\/pnas.0906849106","article-title":"Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957","volume":"106","author":"Liu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1042\/BST20180602","article-title":"H2 influenza viruses: Designing vaccines against future H2 pandemics","volume":"47","author":"Reneer","year":"2019","journal-title":"Biochem. Soc. Trans."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1099\/0022-1317-82-10-2475","article-title":"Antigenic structure of the haemagglutinin of human influenza A\/H2N2 virus","volume":"82","author":"Tsuchiya","year":"2001","journal-title":"J. Gen. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00216-20","DOI":"10.1128\/JVI.00216-20","article-title":"Immune Escape Adaptive Mutations in the H7N9 Avian Influenza Hemagglutinin Protein Increase Virus Replication Fitness and Decrease Pandemic Potential","volume":"94","author":"Chang","year":"2020","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Sitaras, I., Kalthoff, D., Beer, M., Peeters, B., and de Jong, M.C. (2014). Immune escape mutants of Highly Pathogenic Avian Influenza H5N1 selected using polyclonal sera: Identi-fication of key amino acids in the HA protein. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084628"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.virol.2008.03.036","article-title":"Genetically destined potentials for N-linked glycosylation of influenza virus hemagglutinin","volume":"376","author":"Igarashi","year":"2008","journal-title":"Virology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.virol.2009.08.038","article-title":"Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents","volume":"394","author":"Shashkova","year":"2009","journal-title":"Virology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.virol.2010.10.041","article-title":"Characterization of species C human adenovirus serotype 6 (Ad6)","volume":"412","author":"Weaver","year":"2011","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1136\/jcp.2003.014944","article-title":"Heterogeneity of the fibre sequence in subgenus C adenoviruses","volume":"57","author":"Adhikary","year":"2004","journal-title":"J. Clin. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7225","DOI":"10.1128\/JVI.77.13.7225-7235.2003","article-title":"Flexibility of the Adenovirus Fiber Is Required for Efficient Receptor Interaction","volume":"77","author":"Wu","year":"2003","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/14760584.2019.1588113","article-title":"A review of 65 years of human adenovirus seroprevalence","volume":"18","author":"Mennechet","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1128\/JVI.80.4.1688-1699.2006","article-title":"A Novel Adenovirus Type 6 (Ad6)-Based Hepatitis C Virus Vector That Overcomes Preexisting Anti-Ad5 Immunity and Induces Potent and Broad Cellular Immune Responses in Rhesus Macaques","volume":"80","author":"Capone","year":"2006","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e00284-17","DOI":"10.1128\/JVI.00284-17","article-title":"Pathology in Permissive Syrian Hamsters after Infection with Species C Human Adenovirus (HAdV-C) Is the Result of Virus Replication: HAdV-C6 Replicates More and Causes More Pathology than HAdV-C5","volume":"91","author":"Tollefson","year":"2017","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1038\/mt.2011.71","article-title":"Generation of a Kupffer Cell-evading Adenovirus for Systemic and Liver-directed Gene Transfer","volume":"19","author":"Khare","year":"2011","journal-title":"Mol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Alexander, J., Ward, S., Mendy, J., Manayani, D.J., Farness, P., Avanzini, J.B., Guenther, B., Garduno, F., Jow, L., and Snarsky, V. (2012). Pre-Clinical Evaluation of a Replication-Competent Recombinant Adenovirus Serotype 4 Vaccine Expressing Influenza H5 Hemagglutinin. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031177"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e140794","DOI":"10.1172\/JCI140794","article-title":"A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity","volume":"131","author":"Matsuda","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1863-2378.2008.01217.x","article-title":"The role of swine in the generation of novel influenza viruses","volume":"56","author":"Ma","year":"2009","journal-title":"Zoonoses Public Health"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4172\/1747-0862.1000028","article-title":"The pig as a mixing vessel for influenza viruses: Human and veterinary implications","volume":"3","author":"Ma","year":"2009","journal-title":"J. Mol. Genet. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20949","DOI":"10.1073\/pnas.0710286104","article-title":"Identification of H2N3 influenza A viruses from swine in the United States","volume":"104","author":"Ma","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/6\/926\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:27:35Z","timestamp":1760138855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/6\/926"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,10]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["vaccines10060926"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10060926","relation":{},"ISSN":["2076-393X"],"issn-type":[{"type":"electronic","value":"2076-393X"}],"subject":[],"published":{"date-parts":[[2022,6,10]]}}}