Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
0.5 mL suspension in a pre-filled syringe
Approved indication: prevention of Japanese encephalitis
Australian Medicines Handbook section 20.1
Japanese encephalitis is a viral infection transmitted by mosquitoes. Although most infections are asymptomatic, symptomatic infection is often serious and can lead to neurological sequelae or death. The virus has been found throughout Asia and Papua New Guinea and vaccination is indicated for adults who live in or travel to these endemic areas, or who work with the virus in laboratories.
Production of the currently approved vaccine for Japanese encephalitis has been discontinued because of safety concerns regarding hypersensitivity reactions. This was an inactivated vaccine made from Nakayama and SA14-14-2 virus strains propagated in mouse brains. A new inactivated vaccine has been developed in which the virus (strain SA14-14-2) is grown in tissue culture using Vero cells and not in mice.
In a comparative study of the two vaccines, 863 adults received either two intramuscular injections of the Vero cell-derived vaccine (days 0 and 28) or three doses of the vaccine derived from infected mouse brains (days 0, 7 and 28). Efficacy was assessed by measuring titres of virus-specific antibody in serum. The ability of this antibody to neutralise virus was also measured. The seroconversion rate was the percentage of participants whose serum (diluted at least 1:10) reduced the ability of the SA14-14-2 virus to infect a cell monolayer by 50%. Four weeks after the final injection, the seroconversion rate for the test vaccine was similar to that of the comparator (98% vs 95%), and mean antibody titres were twice as high as in the comparator group. (This analysis was done on the per-protocol population of 735 people).1 In a long-term uncontrolled follow-up study, 83% of people who had received a course of the Vero-derived vaccine 12 months earlier (181 vaccinees) had seroconverted. Mean titres had dropped at this time point.2
Systemic adverse reactions to the vaccines were similar, with headache (26%), myalgia (21%), influenza-like illness (13%) and fatigue (13%) being most commonly reported in the Veroderived vaccine group. Localised reactions to the Vero-derived vaccine were much lower than with the comparator. For instance, redness was reported by 1% of people given the Vero-derived vaccine compared to 11% of those given the comparator vaccine. Swelling, hardening and tenderness after injection were also less frequent.1 Similar tolerability to the Vero-derived vaccine was found in a placebo-controlled safety trial of 2650 participants.3
Due to lack of data, this vaccine should not be given to pregnant or breastfeeding women unless it is clearly needed. Likewise, it is not known how safe or effective this vaccine is in children.
Co-administration with inactivated hepatitis A vaccine did not interfere with the immune response to the Vero-derived vaccine. If other vaccines are indicated, injections should be given in the opposite arm. Response may be reduced in people who are immunosuppressed.
The actual effectiveness of this new vaccine is unknown. However, it has been inferred from previous studies that if an individual seroconverts to produce virus-neutralising antibody they will be protected against infection. Based on seroconversion rates in the trials, the vaccine should protect most people from Japanese encephalitis for up to a year. It is not known if further vaccinations will be needed after this.
Another way to assess immunogenicity of the vaccine is to measure cell-mediated immunity (which involves T cells directly and not humoral antibody), an important defence against viruses. There are no data on this from the trials but studies are underway.
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Note on references
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- Tauber E, Kollaritsch H, Korinek M, Rendi-Wagner P, Jilma B, Firbas C, et al. Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial. Lancet 2007;370:1847-53.
- Schuller E, Jilma B, Voicu V, Golor G, Kollaritsch H, Kaltenbock A, et al. Long-term immunogenicity of the new Vero cell-derived, inactivated Japanese encephalitis virus vaccine IC51 six and 12 month results of a multi center follow-up phase 3 study. Vaccine 2008;26:4382-6.
- Tauber E, Kollaritsch H, von Sonnenburg F, Lademann M, Jilma B, Firbas C, et al. Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine. J Infect Dis 2008;198:493-9.