Recent Approaches in Hantavirus Vaccine Development

Piet Maes; Jan Clement; Marc Van Ranst


Expert Rev Vaccines. 2009;8(1):67-76. 

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Expert Commentary

Even though hantaviruses are spread worldwide, with at least 13 viruses causing disease, hantavirus infections are considered rare in most parts of the world, where the incidence of these infections is very low. Nevertheless, hantaviruses can be considered as severe pathogens with case-fatality rates ranging from less than 1% for 'milder' NE caused by Puumala virus, to 6-15% for HFRS caused by the Dobrava-Belgrade virus and Hantaan virus, and over 35% for HPS caused by New World hantaviruses. Phylogeny and epidemiology of hantaviruses are closely linked to those of their respective rodent reservoirs, and both have undergone a long-standing coevolution. This probably explains the marked differences between hantavirus disease spread by the murid subfamilies Arvicolinae (old world voles) and Murinae (old world rats and mice), versus those spread by Neotominae and Sigmodontinae (new world rats and mice), although some common points of clinical presentation exist (see "Symptoms of Hantavirus Disease"). With increasing clinical experience, more points of clinical resemblance, rather than differences, are emerging; for example, renal participation is increasingly documented in South American Andes virus-induced cases.[3,16] Conversely, serious lung participation in HFRS cases has also been described.[4,9,109,110] Moreover, there are preliminary reports describing a tentatively novel and sometimes fatal hantavirus in India causing both renal and lung involvement.[111] With the numerous vaccination-related research publications from the last decade, it has become clear that it should be possible to prevent hantavirus infections by using vaccination. Especially with DNA vaccination and recombinant technology, very promising results have been shown. Another current challenge for researchers, however, is to map all the different hantaviruses circulating in a certain geographical area or country and to identify their pathogenicity to man. Recently, a series of unknown insectivore-borne hantaviruses have been found and described.[112,113,114,115,116] In comparison with their rodent-borne counterparts, these viruses are phylogenetically more distinct from each other. With the discovery of these new insectivore-borne hantaviruses, the total of distinct hantavirus species will go to 28 (22 International Committee on Taxonomy of Viruses-recognized species plus six new insectivore-borne hantavirus species). It is, however, too early to tell if these newfound insectivore-borne hantaviruses are responsible for hantavirus-related disease in their particular geographical region. With the current progression of the techniques to detect hantavirus RNA in a sequence-independent matter, more new hantaviruses will most probably be discovered in the near future; both in areas that are already known to have hantaviruses circulating and in areas for which no data are available. This will, of course, have an impact on hantavirus vaccine development. Moreover, elucidating crossreaction and crossprotection has gained more importance. Hantaviruses form phylogenetically well-separated groups and crossreaction/crossprotection between members of the same phylogenetical group is high. Hantavirus vaccine development must also be viewed from a geographical perspective. A universal hantavirus vaccine will have to consist of at least three different antigenic components to cover for all pathogenic hantaviruses. Moreover, a specific production technology should be selected carefully with the intention that the vaccine can be easily adapted to the current knowledge in the hantavirus field.


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