{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:34:03Z","timestamp":1766990043927,"version":"3.48.0"},"reference-count":83,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T00:00:00Z","timestamp":1766880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>This review highlights the role of temperature sensitivity, a common feature of attenuated virus vaccines, in mediating attenuation. Viral attenuation mechanisms were analyzed by comparing vaccine characteristics and genes with those of wild-type viruses. Development of varicella vaccines, particularly their attenuation and immunogenicity in immunocompromised children, provided key insights into these mechanisms. Temperature sensitivity leads to smaller viral microlesion formation than wild-type virus by impaired viral replication before recognition by the innate immune system, eliciting protective immunity without causing clinical symptoms. Vaccine candidates were selected based on their attenuation in humans and replication ability for mass production, with impaired growth and temperature sensitivity as common characteristics among many vaccines. Temperature-sensitive rhinoviruses replicate in the nasal mucosa at 33 \u00b0C but not in the lungs at 37 \u00b0C, demonstrating in vitro and in vivo temperature sensitivity. Similarly, vaccine-induced immunity arises from viral microlesions caused by impaired growth of temperature-sensitive strains; however, these lesions remain small and result in attenuated clinical symptoms. Because of this impaired growth, higher inoculation doses than those of wild-type strains are required to establish infection and elicit immunity. Therefore, clinical attenuation results from impaired viral replication due to temperature sensitivity, yet it induces protective immune responses.<\/jats:p>","DOI":"10.3390\/v18010048","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:25:51Z","timestamp":1766989551000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temperature-Dependent Viral Pathogenicity: Implications for Attenuation of Viral Vaccines"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-4249","authenticated-orcid":false,"given":"Kimiyasu","family":"Shiraki","sequence":"first","affiliation":[{"name":"Hokuriku Health Service Association, Toyama 930-0177, Japan"},{"name":"Department of Nursing, Senri Kinran University, Osaka 565-0873, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Kawana","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Teikyo University Mizonokuchi Hospital, Kawasaki 213-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-9276","authenticated-orcid":false,"given":"Richard J.","family":"Whitley","sequence":"additional","affiliation":[{"name":"Division of Pediatric Infectious Disease, Department of Pediatrics, Heersink School of Medicine, University of Alabama at Birmingham, 1720 2nd Ave South, Birmingham, AL 35294, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/ccr3.270","article-title":"Identification of ribonucleotide reductase mutation causing temperature-sensitivity of herpes simplex virus isolates from whitlow by deep sequencing","volume":"3","author":"Daikoku","year":"2015","journal-title":"Clin. Case Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1002\/jmv.20990","article-title":"Genital herpes due to acyclovir-sensitive herpes simplex virus caused secondary and recurrent herpetic whitlows due to thymidine kinase-deficient\/temperature-sensitive virus","volume":"79","author":"Shimada","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e29379","DOI":"10.1002\/jmv.29379","article-title":"Vertical mother-to-infant transmission of herpes simplex virus 2 is correlated with tropism due to mutations in viral UL13","volume":"96","author":"Shiraki","year":"2024","journal-title":"J. Med. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1159\/000149876","article-title":"In vivo characteristics of temperature-sensitive host range mutants of herpes simplex virus type 2","volume":"5","author":"Koment","year":"1975","journal-title":"Intervirology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1128\/jvi.15.4.812-819.1975","article-title":"Temperature-sensitive host range mutants of herpes simplex virus type 2","volume":"15","author":"Koment","year":"1975","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1128\/jvi.9.2.223-230.1972","article-title":"Cell-dependent differences in the production of infectious herpes simplex virus at a supraoptimal temperature","volume":"9","author":"Crouch","year":"1972","journal-title":"J. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/0042-6822(75)90088-4","article-title":"Variation in susceptibility of different cell types to temperature-sensitive host range mutants of herpes simplex virus type 2","volume":"64","author":"Koment","year":"1975","journal-title":"Virology"},{"key":"ref_8","unstructured":"(2024, December 03). FLUMIST\u00ae Influenza Vaccine (Live, Attenuated) (7 October). Available online: https:\/\/www.astrazeneca.ca\/content\/dam\/az-ca\/downloads\/productinformation\/flumist-tlaiv-product-monograph-en.pdf."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0042-6822(92)90565-7","article-title":"Correlation of RNA secondary structure and attenuation of Sabin vaccine strains of poliovirus in tissue culture","volume":"189","author":"Macadam","year":"1992","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4972","DOI":"10.1128\/jvi.69.8.4972-4978.1995","article-title":"Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine","volume":"69","author":"Bouchard","year":"1995","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1056\/NEJMoa051016","article-title":"A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults","volume":"352","author":"Oxman","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1016\/S0140-6736(74)90144-5","article-title":"Live vaccine used to prevent the spread of varicella in children in hospital","volume":"2","author":"Takahashi","year":"1974","journal-title":"The Lancet"},{"key":"ref_13","first-page":"25","article-title":"Development of a live attenuated varicella vaccine","volume":"18","author":"Takahashi","year":"1975","journal-title":"Biken J."},{"key":"ref_14","unstructured":"Bektimirov, T.A., Hilleman, M.R., Huygelen, C., Perkins, F.T., Quinnan, G., Schild, G.C., Sizaret, P., and Takahashi, M. (1985). Requirements for Varicella Vaccine (Live) in WHO Expert Committee on Biological Standardization, World Health Organization."},{"key":"ref_15","first-page":"37","article-title":"Attenuation and laboratory markers of the Oka-strain varicella-zoster virus","volume":"61","author":"Takahashi","year":"1985","journal-title":"Postgrad. Med. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1086\/522132","article-title":"Development of varicella vaccine","volume":"197","author":"Takahashi","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"847","DOI":"10.2307\/1591619","article-title":"Attenuation of avian infectious bronchitis virus by cold-adaptation","volume":"35","author":"Gelb","year":"1991","journal-title":"Avian Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Keep, S., Stevenson-Leggett, P., Steyn, A., Oade, M.S., Webb, I., Stuart, J., Vervelde, L., Britton, P., Maier, H.J., and Bickerton, E. (2020). Temperature Sensitivity: A potential method for the generation of vaccines against the avian coronavirus infectious bronchitis virus. Viruses, 12.","DOI":"10.3390\/v12070754"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1099\/0022-1317-79-8-1895","article-title":"Mutation in NS5 protein attenuates mouse neurovirulence of yellow fever 17D vaccine virus","volume":"79","author":"Xie","year":"1998","journal-title":"J. Gen. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"331","DOI":"10.7883\/yoken1952.36.331","article-title":"Temperature-dependent growth restriction in measles vaccine strains","volume":"36","author":"Fukuda","year":"1983","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.vaccine.2005.06.036","article-title":"The phosphoprotein of attenuated measles AIK-C vaccine strain contributes to its temperature-sensitive phenotype","volume":"24","author":"Komase","year":"2006","journal-title":"Vaccine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.virusres.2016.10.003","article-title":"Mechanisms of temperature sensitivity of attenuated Urabe mumps virus","volume":"227","author":"Schinkel","year":"2017","journal-title":"Virus Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1128\/jvi.70.1.580-584.1996","article-title":"Temperature-sensitive phenotype of the human parainfluenza virus type 3 candidate vaccine strain (cp45) correlates with a defect in the L gene","volume":"70","author":"Ray","year":"1996","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/0168-1702(92)90049-F","article-title":"Cold-passaged human parainfluenza type 3 viruses contain ts and non-ts mutations leading to attenuation in rhesus monkeys","volume":"22","author":"Hall","year":"1992","journal-title":"Virus Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1093\/infdis\/jiaa049","article-title":"Live-attenuated respiratory syncytial virus vaccine with M2-2 deletion and with small hydrophobic noncoding region is highly immunogenic in children","volume":"221","author":"McFarland","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1093\/infdis\/jiy066","article-title":"Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children","volume":"217","author":"Buchholz","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1099\/0022-1317-71-10-2369","article-title":"A single amino acid substitution in the large subunit of herpes simplex virus type 1 ribonucleotide reductase which prevents subunit association","volume":"71","author":"Nikas","year":"1990","journal-title":"J. Gen. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1099\/0022-1317-73-6-1417","article-title":"Expression of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is required for virus growth and neoplastic transformation","volume":"73","author":"Smith","year":"1992","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1006\/viro.1995.0033","article-title":"Intracellular localisation of herpes simplex virus type 1 ribonucleotide reductase subunits during infection of cultured cells","volume":"213","author":"Conner","year":"1995","journal-title":"Virology"},{"key":"ref_30","first-page":"458","article-title":"The herpes simplex virus type 1 temperature-sensitive mutant ts1222 has a single base pair deletion in the small subunit of ribonucleotide reductase","volume":"167","author":"Preston","year":"1988","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1128\/AAC.48.9.3343-3348.2004","article-title":"Novel murine model of pneumococcal pneumonia: Use of temperature as a measure of disease severity to compare the efficacies of moxifloxacin and levofloxacin","volume":"48","author":"Bast","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1600-0781.1996.tb00210.x","article-title":"Effects of near-infrared radiation on the epidermal proliferation and cutaneous immune function in mice","volume":"12","author":"Danno","year":"1996","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1128\/jvi.24.2.470-477.1977","article-title":"Herpes simplex virus DNA polymerase as the site of phosphonoacetate sensitivity: Temperature-sensitive mutants","volume":"24","author":"Purifoy","year":"1977","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0167-4781(87)90097-2","article-title":"Alkaline nuclease activity in cells infected with herpes simplex virus type 1 (HSV-1) and HSV-1 temperature-sensitive mutants","volume":"910","author":"Hafner","year":"1987","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1128\/jvi.45.1.343-353.1983","article-title":"Genetic analysis of temperature-sensitive mutants which define the genes for the major herpes simplex virus type 2 DNA-binding protein and a new late function","volume":"45","author":"Dixon","year":"1983","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/0042-6822(84)90349-0","article-title":"Characterisation of a herpes simplex virus type 1 mutant which has a temperature-sensitive defect in penetration of cells and assembly of capsids","volume":"138","author":"Addison","year":"1984","journal-title":"Virology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1128\/jvi.52.3.767-776.1984","article-title":"Temperature-sensitive mutants in herpes simplex virus type 1 ICP4 permissive for early gene expression","volume":"52","author":"DeLuca","year":"1984","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/0042-6822(84)90230-7","article-title":"Genome locations of temperature-sensitive mutants in glycoprotein gB of herpes simplex virus type 1","volume":"137","author":"DeLuca","year":"1984","journal-title":"Virology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1542\/peds.71.3.307","article-title":"Live attenuated varicella vaccine: The KMcC strain in healthy children","volume":"71","author":"Arbeter","year":"1983","journal-title":"Pediatrics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3181\/00379727-166-41071","article-title":"Clinical and laboratory studies of KMcC strain live attenuated varicella virus","volume":"166","author":"Neff","year":"1981","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1099\/0022-1317-69-5-1091","article-title":"The effect of sequences in the 5\u2032 non-coding region on the replication of polioviruses in the human gut","volume":"69","author":"Minor","year":"1988","journal-title":"J. Gen. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5278","DOI":"10.1128\/jvi.69.9.5278-5286.1995","article-title":"Mapping of mutations contributing to the temperature sensitivity of the Sabin 1 vaccine strain of poliovirus","volume":"69","author":"Georgescu","year":"1995","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4630","DOI":"10.1128\/jvi.67.8.4630-4638.1993","article-title":"A mutation in the RNA polymerase of poliovirus type 1 contributes to attenuation in mice","volume":"67","author":"Blondel","year":"1993","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0042-6822(91)90877-E","article-title":"The 5\u2032 noncoding region of the type 2 poliovirus vaccine strain contains determinants of attenuation and temperature sensitivity","volume":"181","author":"Macadam","year":"1991","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4922","DOI":"10.1128\/jvi.64.10.4922-4929.1990","article-title":"Mapping of mutations associated with neurovirulence in monkeys infected with Sabin 1 poliovirus revertants selected at high temperature","volume":"64","author":"Christodoulou","year":"1990","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1006\/viro.2000.0354","article-title":"Studies on the attenuation phenotype of polio vaccines: Poliovirus RNA polymerase derived from Sabin type 1 sequence is temperature sensitive in the uridylylation of VPg","volume":"272","author":"Paul","year":"2000","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1046\/j.1365-2273.2002.00544.x","article-title":"Nasal mucosal temperature during respiration","volume":"27","author":"Lindemann","year":"2002","journal-title":"Clin. Otolaryngol. Allied Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1097\/00005537-200004000-00021","article-title":"Temperature profile in the nasal cavity","volume":"110","author":"Keck","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1152\/jappl.1985.58.2.564","article-title":"Thermal mapping of the airways in humans","volume":"58","author":"McFadden","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1002\/(SICI)1096-9071(199905)58:1<100::AID-JMV16>3.0.CO;2-D","article-title":"Rhinoviruses replicate effectively at lower airway temperatures","volume":"58","author":"Papadopoulos","year":"1999","journal-title":"J. Med. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/rmv.406","article-title":"Rhinovirus and the lower respiratory tract","volume":"14","author":"Hayden","year":"2004","journal-title":"Rev. Med. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1086\/313723","article-title":"Pneumonia caused by rhinovirus","volume":"30","author":"Imakita","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/infdis\/152.5.863","article-title":"Viral replication and immunologic responses in children naturally infected with varicella-zoster virus and in varicella vaccine recipients","volume":"152","author":"Asano","year":"1985","journal-title":"J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/infdis\/149.4.501","article-title":"Biologic and immunologic characterization of the soluble skin-test antigen of varicella-zoster virus","volume":"149","author":"Shiraki","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1093\/infdis\/143.5.684","article-title":"Soluble skin test antigen of varicella-zoster virus prepared from the fluid of infected cultures","volume":"143","author":"Asano","year":"1981","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/infdis\/136.6.784","article-title":"Diagnostic skin test reactions with varicella virus antigen and clinical application of the test","volume":"136","author":"Kamiya","year":"1977","journal-title":"J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1542\/peds.56.3.388","article-title":"Varicella in children with cancer: Seventy-seven cases","volume":"56","author":"Feldman","year":"1975","journal-title":"Pediatrics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1093\/infdis\/149.6.956","article-title":"Biologic and biophysical markers of a live varicella vaccine strain (Oka): Identification of clinical isolates from vaccine recipients","volume":"149","author":"Hayakawa","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11447","DOI":"10.1128\/JVI.76.22.11447-11459.2002","article-title":"Comparison of the complete DNA sequences of the Oka varicella vaccine and its parental virus","volume":"76","author":"Gomi","year":"2002","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1086\/379835","article-title":"Pathogenetic tropism of varicella-zoster virus to primary human hepatocytes and attenuating tropism of Oka varicella vaccine strain to neonatal dermal fibroblasts","volume":"188","author":"Shiraki","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"S320","DOI":"10.1093\/infdis\/174.Supplement_3.S320","article-title":"Varicella vaccine for immunocompromised children: Results of collaborative studies in the United States and Canada","volume":"174","author":"LaRussa","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1056\/NEJM199111283252204","article-title":"The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group","volume":"325","author":"Hardy","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S0140-6736(76)92397-7","article-title":"Use of live varicella vaccine in children with acute leukaemia or other malignancies","volume":"2","author":"Hattori","year":"1976","journal-title":"The Lancet"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"7601","DOI":"10.1128\/jvi.69.12.7601-7605.1995","article-title":"Role of mutations G-480 and C-6203 in the attenuation phenotype of Sabin type 1 poliovirus","volume":"69","author":"McGoldrick","year":"1995","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0092-1157(79)80020-7","article-title":"Pattern of plaquing efficiency at different temperatures (PPET) as a differentiation tool among poliovirus type 3 Leon 12a1b progenies and its possible use as a genetic marker","volume":"7","author":"Yoshii","year":"1979","journal-title":"J. Biol. Stand."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s11262-010-0448-9","article-title":"Growth kinetic analysis of bi-recombinant poliovirus vaccine strains","volume":"40","author":"Pliaka","year":"2010","journal-title":"Virus Genes"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1016\/S0264-410X(98)00471-X","article-title":"Safety of a trivalent live attenuated intranasal influenza vaccine, FluMist, administered in addition to parenteral trivalent inactivated influenza vaccine to seniors with chronic medical conditions","volume":"17","author":"Jackson","year":"1999","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1128\/JCM.38.2.839-845.2000","article-title":"Genotypic stability of cold-adapted influenza virus vaccine in an efficacy clinical trial","volume":"38","author":"Cha","year":"2000","journal-title":"J. Clin. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1002\/(SICI)1099-1654(199910\/12)9:4<237::AID-RMV252>3.0.CO;2-G","article-title":"The development of live attenuated cold-adapted influenza virus vaccine for humans","volume":"9","author":"Maassab","year":"1999","journal-title":"Rev. Med. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1056\/NEJM199805143382002","article-title":"The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children","volume":"338","author":"Belshe","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0042-6822(02)00035-1","article-title":"Multiple amino acid residues confer temperature sensitivity to human influenza virus vaccine strains (FluMist) derived from cold-adapted A\/Ann Arbor\/6\/60","volume":"306","author":"Jin","year":"2003","journal-title":"Virology"},{"key":"ref_72","unstructured":"(2025, May 01). CDC Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine), Available online: https:\/\/www.cdc.gov\/flu\/vaccine-types\/nasalspray.html."},{"key":"ref_73","first-page":"43","article-title":"Protective effect of immediate inoculation of a live varicella vaccine in household contacts in relation to the viral dose and interval between exposure and vaccination","volume":"25","author":"Asano","year":"1982","journal-title":"Biken J."},{"key":"ref_74","unstructured":"Biken (2025, December 07). Varicella Vaccine Live Attenuated \u201cBIKEN\u201d. Available online: https:\/\/www.biken.or.jp\/upload\/product\/document_pdf\/fa-v\/document_mt.pdf."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/imcb.12253","article-title":"The role of Langerhans cells in pathologies of the skin","volume":"97","author":"Rajesh","year":"2019","journal-title":"Immunol. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Shiraki, K., Yasumoto, S., Toyama, N., and Fukuda, H. (2021). Amenamevir, a helicase-primase inhibitor, for the optimal treatment of herpes zoster. Viruses, 13.","DOI":"10.3390\/v13081547"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"108121","DOI":"10.1016\/j.pharmthera.2022.108121","article-title":"Antiviral therapy for COVID-19: Derivation of optimal strategy based on past antiviral and favipiravir experiences","volume":"235","author":"Shiraki","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1128\/JVI.02061-09","article-title":"Antibody to varicella-zoster virus immediate-early protein 62 augments allodynia in zoster via brain-derived neurotrophic factor","volume":"84","author":"Hama","year":"2010","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1086\/510206","article-title":"Recommendations for the management of herpes zoster","volume":"44","author":"Dworkin","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00404-006-0234-z","article-title":"Single-day therapy: An expert opinion on a recent development for the episodic treatment of recurrent genital herpes","volume":"275","author":"Tyring","year":"2007","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1542\/peds.54.2.136","article-title":"Photodistribution of viral exanthems","volume":"54","author":"Gilchrest","year":"1974","journal-title":"Pediatrics"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"114316","DOI":"10.1016\/j.bcp.2020.114316","article-title":"Detection of viral infections by innate immunity","volume":"183","author":"Carty","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"314","DOI":"10.3390\/v2010314","article-title":"Herpesviruses and autophagy: Catch me if you can!","volume":"2","author":"Cavignac","year":"2010","journal-title":"Viruses"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/48\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:29:50Z","timestamp":1766989790000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/48"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,28]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["v18010048"],"URL":"https:\/\/doi.org\/10.3390\/v18010048","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,28]]}}}