{"version":"1.0","provider_name":"TBE Book","provider_url":"https:\/\/tbenews.com\/tbe","author_name":"IT","author_url":"https:\/\/tbenews.com\/tbe\/author\/brianong\/","title":"Chapter 15: TBE vaccines licensed around the globe - TBE Book","type":"rich","width":600,"height":338,"html":"<blockquote class=\"wp-embedded-content\" data-secret=\"91x1ox4oqT\"><a href=\"https:\/\/tbenews.com\/tbe\/chapter-15-tbe-vaccines-licensed-around-the-globe\/\">Chapter 15: TBE vaccines licensed around the globe<\/a><\/blockquote><iframe sandbox=\"allow-scripts\" security=\"restricted\" src=\"https:\/\/tbenews.com\/tbe\/chapter-15-tbe-vaccines-licensed-around-the-globe\/embed\/#?secret=91x1ox4oqT\" width=\"600\" height=\"338\" title=\"&#8220;Chapter 15: TBE vaccines licensed around the globe&#8221; &#8212; TBE Book\" data-secret=\"91x1ox4oqT\" frameborder=\"0\" marginwidth=\"0\" marginheight=\"0\" scrolling=\"no\" class=\"wp-embedded-content\"><\/iframe><script>\n\/*! This file is auto-generated *\/\n!function(d,l){\"use strict\";l.querySelector&&d.addEventListener&&\"undefined\"!=typeof URL&&(d.wp=d.wp||{},d.wp.receiveEmbedMessage||(d.wp.receiveEmbedMessage=function(e){var t=e.data;if((t||t.secret||t.message||t.value)&&!\/[^a-zA-Z0-9]\/.test(t.secret)){for(var s,r,n,a=l.querySelectorAll('iframe[data-secret=\"'+t.secret+'\"]'),o=l.querySelectorAll('blockquote[data-secret=\"'+t.secret+'\"]'),c=new RegExp(\"^https?:$\",\"i\"),i=0;i<o.length;i++)o[i].style.display=\"none\";for(i=0;i<a.length;i++)s=a[i],e.source===s.contentWindow&&(s.removeAttribute(\"style\"),\"height\"===t.message?(1e3<(r=parseInt(t.value,10))?r=1e3:~~r<200&&(r=200),s.height=r):\"link\"===t.message&&(r=new URL(s.getAttribute(\"src\")),n=new URL(t.value),c.test(n.protocol))&&n.host===r.host&&l.activeElement===s&&(d.top.location.href=t.value))}},d.addEventListener(\"message\",d.wp.receiveEmbedMessage,!1),l.addEventListener(\"DOMContentLoaded\",function(){for(var e,t,s=l.querySelectorAll(\"iframe.wp-embedded-content\"),r=0;r<s.length;r++)(t=(e=s[r]).getAttribute(\"data-secret\"))||(t=Math.random().toString(36).substring(2,12),e.src+=\"#?secret=\"+t,e.setAttribute(\"data-secret\",t)),e.contentWindow.postMessage({message:\"ready\",secret:t},\"*\")},!1)))}(window,document);\n\/\/# sourceURL=https:\/\/tbenews.com\/tbe\/wp-includes\/js\/wp-embed.min.js\n<\/script>\n","thumbnail_url":"https:\/\/tbenews.com\/tbe\/wp-content\/uploads\/2024\/06\/Chapter-15-TBE-VAACINE-LICENSED_-scaled.jpg","thumbnail_width":2560,"thumbnail_height":1435,"description":"Chapter 15:TBE vaccines licensed aroundthe globe Eva Maria P\u00f6llabauer&nbsp;and Herwig Kollaritsch Key points Active immunization The first generation of TBE vaccines was produced in Russia. These vaccines were based on the TBEV-FE strain Sofjin, and were mouse-brain propagated. Over several decades, formulations and growth media were adapted step-by-step to result in the currently used TBE vaccines, details of which are summarized in Table 1. The two so called \u2018Western vaccines\u2019 are FSME-IMMUN, which is licensed through the mutual recognition procedure (MRP) of the European Medicines Agency (EMA), and Encepur, which has several national licenses. These two vaccines are distributed mainly in Europe and Israel, while the other TBE vaccines are predominantly produced for local markets. Since 2021 FSME-IMMUN is also licensed in the USA under the name TICOVAC. Manufacturer and products TBE vaccines are produced commercially by five manufacturers. Two are produced in Europe, one by Pfizer (Vienna, Austria), one by GSK Vaccines (Marburg, Germany; bought by Bavarian Nordic, Kvistgaard, Denmark end 2019); 2 in Russia: IPVE (Moscow, Russia) and Microgen (Tomsk, Russia); and one in China: Sen Tai Bao (Changchun Institute of Biological Products Co., Ltd.; CIBP). The two manufacturers in Europe use very similar manufacturing processes but different virus strains and stabilizers. Both of them have licensed formulations for adults (Pfizer: FSME-IMMUN; Bavarian Nordic: Encepur) and for children older than one year (Pfizer: FSME-IMMUN Junior; Bavarian Nordic: Encepur-Children). FSME-IMMUN Junior is licensed for children up to and including 15 years of age, whereas Encepur-Children is licensed up to and including twelve years of age. In some countries, FSME-IMMUN is marketed as TicoVac. FSME-IMMUN, Encepur as well as EnceVir have (half dose) formulations for children and the TBE-Moscow vaccine is approved for use in children age 3 years or older. Human serum albumin (HSA) is used as a stabilizer by Pfizer, IPVE, CIBP, and Microgen, whereas Bavarian Nordic uses an increased amount of sucrose for this purpose. An overview of the excipients of the European and Russian vaccines is shown in Table 1. FSME-IMMUN This vaccine is based on the Austrian TBE strain Neud\u00f6rfl (TBEV-Eu) and was licensed first in 1976. The virus was primarily passaged in the brains of specific pathogen-free (SPF) baby mice and then propagated in primary SPF chicken embryo cells. The vaccine formulation underwent several changes over subsequent decades until 2000. The actual licensed vaccine is a formaldehyde-inactivated, whole-virus vaccine (2.4 mcg antigen per dose), adjuvanted with aluminum hydroxide and containing HSA as an essential stabilizer. Details of the actual formulation are described in Table 1. A pediatric formulation containing half of the adult dose (FSME-IMMUN Junior) was licensed in 2002. The current manufacturer of FSME-IMMUN is Pfizer. Encepur This vaccine is based on the European subtype virus strain K23, isolated in Karlsruhe in southern Germany and originally licensed first in Germany in 1991 as Encepur by Chiron Behring, Marburg, Germany.1 Similar to FSME-IMMUN, the seed virus for this vaccine is grown on primary chick embryo cells. The virus is inactivated by formaldehyde, adsorbed to aluminum hydroxide, and contains 1.5 mcg of antigen. A pediatric formulation containing half the adult dose (Table 1) has been available since 1994.2&nbsp; The genomic sequence of the K23 vaccine virus in the Encepur formulation has mutations compared to the originally published sequence.90 However, the clinical impact of the modified primary amino acid sequence is unknown. In the year end of 2019 Bavarian Nordic acquired Encepur from GSK. According to communications by GSK and Bavarian Nordic, vaccine manufacturing will be transferred over the next 5 years, sales and marketing responsibility was assumed in 2020. Russian vaccines Three TBE vaccines have been developed and are marketed in Russia (see Chapter 13: Russia). All of them are cultured on chick embryo cells and are formalin-inactivated. EnceVir, manufactured by Microgen, Tomsk, is based on the TBEV-FE subtype strain 205.4 There is a vaccine for adults (EnceVir (0.5) and as of 2014 also a pediatric formulation (EnceVir Neo (0.25) for children 3-17 years). Klesch-E-Vac is based on the TBEV-Fe prototype strain Sofjin, and manufactured by the Federal State Enterprise of Chumakov Institute of Poliomyelitis and Viral Encephalitides (IPVE). It is provided as a suspension for injection.3 Klesch-E-Vac has an adult (0.5mL) and also a pediatric formulation licensed for use as of 12 months to 16 years of age (half of the adult dose, i.e. 0.25 mL). In addition, there is a dry-lyophilized TBE-Moscow vaccine (no specific trade name), based on the Sofjin strain.3 The producer is also the Federal State Enterprise of Chumakov Institute of Poliomyelitis and Viral Encephalitides (IPVE). The product is approved for use in patients from 3 years of age as a unified formulation. Sen Tai Bao The Sen Tai Bao (Changchun Institute of Biological Products Co. Ltd: CIBP; in Changchun, Jilin Province, China) TBE vaccine is manufactured by the Changchun Institute of Biological Products (CIBP) and marketed in China only.5 There a first vaccine against TBE was developed in 1953, by propagating the TBEV on mouse brain tissue followed by inactivation. It was an inactivated TBEV grown on infected mouse brain tissues. Between 1953 and now several vaccine formulations have been developed and used. Some of the earlier vaccines were grown on chicken embryo cells.91 The current formalin-inactivated vaccine formulation is based on the TBEV-FE Mori-Jang strain, grown on monolayer gopher kidney cells. It uses HSA as the stabilizer and aluminum hydroxide as adjuvant and thiomersal as preservative. This vaccine has been approved for use in adults and children 8 years of age or older since 2004.6 To reduce reactogenicity, it is recommended to add 0.2 mL of sodium bisulfite solution to each 5 mL dose, which will turn the color of the product from red to yellow.&nbsp; The vaccine should be administered subcutaneously into the lateral deltoid muscle region. First and second injections are administered 7-10 days apart, the third and following doses are given annually. Dosing by age is done by volume adjustment, i.e. children 2-6 years receive 0.5 mL\/dose; 7-10 years 1.0 mL\/dose; and 11-15 years"}