We read with interest the article 'Indian vaccine trial raises spectre of new disease'. As the manufacturers of the Japanese encephalitis vaccine in question — ChimeriVax-JE — we wish to point out several misleading statements in the article.
There are no scientific data to support the statement that the vaccine could "introduce a new disease or make an existing virus more deadly".
The theoretical concern that live flavivirus vaccines (such as ChimeriVax-JE) could combine genes with wild flaviviruses has been extensively debated in the literature and has little foundation (see Lancet 364, 500; Lancet 364, 499; Lancet 364, 498; Vaccine 23, 2956).
The use of ChimeriVax-JE cannot result in the introduction or generation of yellow fever virus. The vaccine was made by swapping the envelope genes of the weakened yellow fever vaccine strain 17D with the corresponding genes of the weakened SA14-14-2 vaccine strain of the Japanese encephalitis virus.
Numerous pre-clinical and human safety studies have shown that ChimeriVax-JE is more attenuated (that is, weaker) than the time-tested and safe 17D yellow fever vaccine. The yellow fever 17D virus itself was not used at any stage during the manufacture of ChimeriVax-JE.
The article states: "Problems would arise, says Banerjee, if a mosquito fed on a vaccinated person and picked up ChimeriVax-JE, and if the vaccine virus recombined with any of the other flaviviruses within that mosquito."
Several pre-clinical studies conducted independently by the US Centers for Disease Control and Prevention and the Australian Army Malaria Institute have shown that our vaccine
[ok?] is incapable of infecting mosquitoes orally, in contrast to wtJE or the SA14-14-2 strain of Japanese encephalitis from in the vaccine used in China.
Our vaccine cannot replicate in head tissue, which is a prerequisite for infecting vertebrates (American Journal of Tropical Medicine and Hygiene 62, 480).
Even if mosquitoes were susceptible to ChimeriVax-JE, the observed concentration of weakened virus in vaccinated humans would be about 100 times too low for transmission to occur, as research has shown (Journal of Infectious Diseases 188, 1213).
The article also states: "The risk associated with the emergence of a pathogenic virus during mass vaccination following recombination between ChimeriVax-JE and another flavivirus, however small, cannot be ignored."
We agree. However, all scientific data to date indicate that if possible, the theoretical risk of recombination in a manner that creates a viable virus capable of replication and survival is extremely low.
Again, we do not mean to minimise this issue — indeed, we have conducted considerable experimentation to investigate this possibility, and have found such a recombination event to be below levels of detection under the most favourable experimental conditions to detect such an event.
Moreover, the risk of this theoretical event, when viewed in the light of the individual and public health benefits of vaccination with ChimeriVax-JE, should be no reason for concern.
The article states: "The trial was originally due to take place last year in Thailand. A senior official of the Thai Ministry of Health told SciDev.Net that the World Health Organization (WHO) did not support the trial and that it was eventually abandoned for no clear reason. The vaccine manufacturer Acambis declined to reply when asked why it moved the trial to India."
Regarding clinical trial work with ChimeriVax-JE in Thailand, a Memorandum of Understanding with the WHO provided full support for the trial and approved its initiation. However, based on the magnitude of recent outbreaks of Japanese encephalitis in India, it was decided that India should be given priority for public health reasons. India has a much larger burden of Japanese encephalitis than Thailand and lacks sufficient vaccine supplies.
These factors convinced Acambis and the government of India of the urgent need for a new second-generation JE vaccine that could be supplied affordably in sufficient quantities to meet the country's needs. In addition to the public health needs of India, priority was also given to India due to the local partnership with Bharat Biotech, which will be involved in manufacturing the product, as well as a strong relationship with the Indian scientific community at the highest level.Acambis is very grateful for the extensive level of support it has received for developing ChimeriVax-JE in India. We will continue to develop this product with the support of its collaborators and the review and approval of the appropriate regulatory and ethical committees in India.