Tick-borne encephalitis vaccine (whole virus, inactivated)

Identification

Summary

Tick-borne encephalitis vaccine (whole virus, inactivated) is a whole inactivated viral vaccine against meningoencephalitis caused by the tick-borne encephalitis virus.

Generic Name
Tick-borne encephalitis vaccine (whole virus, inactivated)
DrugBank Accession Number
DB16611
Background

Tick-borne encephalitis (TBE) is a disease caused by the TBE virus (TBEV), transmitted by ticks from the genus Ixodes. The disease course is variable. Some patients will be asymptomatic or experience a mild febrile illness, while others will experience the full course including neurological symptoms.1 TBE often manifests in a biphasic manner, with patients experiencing a flu-like illness followed by a variable asymptomatic period and then a second phase characterized by various neurological symptoms falling under the categorizations of meningitis, diffuse/focal meningoencephalitis, and meningoencephalomyelitis.1,4 While some patients recover fully following neurological TBE, neurological sequelae can last for years and rare chronic forms of the disease have also been noted.4 Due to a paucity of effective safe and effective acute therapeutic agents, vaccination remains the most important defence against TBE in endemic areas.4

TICOVAC (also known as TicoVac or FSME-IMMUN) was the first approved vaccine against TBE in Europe, first approved in 1976.4,5 A second very similar vaccine, Encepur, followed in 1991.4 Both vaccines are based on formaldehyde-inactivated whole virus.4,7 Although TICOVAC was originally based on a master seed virus passaged in mouse brain and then propagated in chicken embryo fibroblast (CEF) cells, since the 1990's, the whole process has been carried out in CEF cells only.4

Originally developed by Baxter International Inc., TICOVAC was subsequently acquired by Pfizer Inc. in 2014.8 TICOVAC was granted FDA approval on August 13, 2021.7

Type
Biotech
Groups
Approved
Biologic Classification
Vaccines
Inactivated
Synonyms
  • TBE vaccine
  • Tick-borne encephalitis vaccine

Pharmacology

Indication

TICOVAC is indicated for active immunization against tick-borne encephalitis (TBE) in patients one year of age and older.7

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Tick-borne encephalitis (TBE) vaccines induce a neutralizing antibody response against the TBE virus (TBEV).5,7 They can be administered by either a standard schedule, with two doses roughly 1-3 months apart and a third dose within the following 12 months, or by a rapid schedule, in which the first two doses are given within two weeks and the third dose anywhere from 5-18 months later.4,5 As the immunity offered wanes over time, especially in older patients, it is recommended to administer a booster every 3-5 years following initial immunization.4,5 Although TBE vaccines have a good safety profile, there have been reports of anaphylactic reactions following administration. In addition, the TICOVAC vaccine contains albumin, allowing for an extremely remote risk of viral disease transmission and variant Creutzfeldt-Jakob disease (vCJD) following vaccine administration.7 Like other vaccines, TBE vaccines may not protect individuals with an impaired/altered immune system to the same extent; there have been reports of breakthrough infections, even in fully vaccinated individuals.4,7

Mechanism of action

Tick-borne encephalitis (TBE) is a viral infection caused by the TBE virus (TBEV) with an endemic range spreading throughout Europe and into Russia, China, and other parts of Asia. The three main subtypes are transmitted by two distinct species of Ixodes tick, with the European subtype (TBEV-Eu) transmitted by I. ricinus and both the Siberian (TBEV-Sib) and the Far Eastern (TBEV-FE) subtypes transmitted by I. persulcatus.1 All three subtypes are members of the Flavivirus genus within the Flaviviridae family, which also contains other clinically relevant flaviviruses including Zika, West Nile, and dengue.1,2

Like other flaviviruses, TBEV particles are membrane/protein-bound, smooth spheres roughly 50 nm in diameter enclosing a single copy of the ~11 kb positive-strand RNA genome. This genome encodes three structural (envelope (E), membrane (M), and capsid (C) proteins) and seven non-structural (NNS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins required for the intracellular assembly of new TBEV particles.2,3 The particle consists of a nucleocapsid (the viral genome associated with multiple copies of the C protein) surrounded by a membrane in which E and M proteins are embedded to form an icosahedrally-symmetric protein coat.2 Extracellular TBEV particles interact with an as yet undefined receptor to achieve endocytic uptake; once inside the acidic environment of the endosome, the E protein is protonated and undergoes extensive rearrangement to reveal a "fusion loop" that mediates TBEV membrane fusion and the release of the nucleocapsid, which subsequently disassociates to release free viral RNA.2,3 Viral replication and particle assembly, involving both viral and host factors, occurs in the ER, followed by the trafficking of viral particles through the trans-Golgi network (TGN), further particle processing, and eventual extracellular release.2,3

The ability of TBEV to cross the blood-brain barrier and cause neurological symptoms (neurovirulence) has been correlated with several factors, namely solvent-exposed residues within the E protein, which also represent the primary target for neutralizing antibodies.3,4 These likely work through inhibiting host cell receptor binding, inhibiting endosomal fusion, or through Fc-mediated clearance of infected cells. Non-neutralizing, though still protective, antibodies have also been described against the NS1 protein, which also likely mediate clearance of infected cells through antibody-dependent cell-mediated cytotoxicity or the complement system.4

TBE vaccines contain inactivated whole virus, either of the Neudoerfl or Karlsruhe (K23) strains of the TBEV-Eu subtype, and induce a strong neutralizing antibody seroconversion rate in fully immunized individuals.4,7 Despite genetic differences between the subtypes, they are similar enough to produce effective cross-immunity for the TBEV-Sib and TBEV-FE subtypes in individuals vaccinated with a vaccine derived from the TBEV-Eu subtype.5

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

This vaccine has not been evaluated for carcinogenicity, genotoxicity, or impairment of fertility.7

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
International/Other Brands
FSME-Immun / TicoVac (Pfizer Inc.)

Categories

Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
Not Available
CAS number
Not Available

References

General References
  1. Lindquist L, Vapalahti O: Tick-borne encephalitis. Lancet. 2008 May 31;371(9627):1861-71. doi: 10.1016/S0140-6736(08)60800-4. [Article]
  2. Pulkkinen LIA, Butcher SJ, Anastasina M: Tick-Borne Encephalitis Virus: A Structural View. Viruses. 2018 Jun 28;10(7). pii: v10070350. doi: 10.3390/v10070350. [Article]
  3. Velay A, Paz M, Cesbron M, Gantner P, Solis M, Soulier E, Argemi X, Martinot M, Hansmann Y, Fafi-Kremer S: Tick-borne encephalitis virus: molecular determinants of neuropathogenesis of an emerging pathogen. Crit Rev Microbiol. 2019 Aug;45(4):472-493. doi: 10.1080/1040841X.2019.1629872. Epub 2019 Jul 3. [Article]
  4. Ruzek D, Avsic Zupanc T, Borde J, Chrdle A, Eyer L, Karganova G, Kholodilov I, Knap N, Kozlovskaya L, Matveev A, Miller AD, Osolodkin DI, Overby AK, Tikunova N, Tkachev S, Zajkowska J: Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines. Antiviral Res. 2019 Apr;164:23-51. doi: 10.1016/j.antiviral.2019.01.014. Epub 2019 Jan 31. [Article]
  5. Loew-Baselli A, Poellabauer EM, Pavlova BG, Fritsch S, Firth C, Petermann R, Barrett PN, Ehrlich HJ: Prevention of tick-borne encephalitis by FSME-IMMUN vaccines: review of a clinical development programme. Vaccine. 2011 Oct 6;29(43):7307-19. doi: 10.1016/j.vaccine.2011.07.089. Epub 2011 Aug 16. [Article]
  6. BASG: FSME-Immun 0,5 ml Erwachsene Injektionssuspension in einer Fertigspritze (Tick-born encephalitis inactivated virus vaccine) Intramuscular Injection [Link]
  7. FDA Approved Drug Products: TICOVAC (Tick-Borne Encephalitis vaccine) injection [Link]
  8. Pfizer Press Release: Acquisition of Baxter Vaccines [Link]
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionTick Borne Encephalitis (TBE)1
4CompletedBasic ScienceTick Borne Encephalitis (TBE)1
4CompletedPreventionTick Born Encephalitis1
4CompletedPreventionTick Borne Encephalitis (TBE)6
4CompletedPreventionVaccine Responsiveness During Allergy De-sensitization Treatment / Vaccine Responsiveness in Allergy1
4CompletedTreatmentTick Borne Encephalitis (TBE)1
4Not Yet RecruitingPreventionTick Borne Encephalitis (TBE) / Vaccines1
3Active Not RecruitingPreventionTick Borne Encephalitis (TBE)1
3CompletedPreventionInfluenza, Human1
3CompletedPreventionTick Borne Encephalitis (TBE)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, suspensionParenteral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Drug created on February 16, 2021 21:02 / Updated on August 28, 2021 08:41