Caution about Newcastle Disease Virus-Based Live Attenuated Vaccine

Abstract

In several recent papers, two published last year in the Journal of Virology by DiNapoli et al. (3) and Ge et al. (4), an earlier study by Martinez-Sobrido et al. in 2006 (6), and a review by Bukreyev et al. in 2006 (1), Newcastle disease virus (NDV) is proposed as a potential vector in the development of a novel bi- or multivalent vaccine. We question whether those studies satisfactorily address the possibility of genetic exchange involving nonsegmented negative-strand RNA viruses such as NDV. In fact, powerful evidence of recombination in NDV was first found as early as 2003 (2). Two recent studies (5, 8) further demonstrated recombination events in NDV. In particular, a natural multirecombinant was identified, which shows that the recombination rate might not be low, at least in NDV (5). It has also been found that NDV live attenuated vaccines have the capacity to play roles in shaping NDV evolution by homologous recombination with wild-type virus (5). In addition, there is more and more evidence of homologous recombination involving other nonsegmented negative-strand RNA viruses like Zaire Ebola virus (10), measles virus (9), mumps virus (2), canine distemper virus (7), etc. Unfortunately, neither recombination between a vaccine virus and other circulating nonsegmented negative-strand RNA viruses resulting in untoward recombinants nor potential instability of the inserted foreign gene was fully addressed and evaluated in these studies. We should never entirely dismiss the possibility of untoward recombination events. Safety issues with respect to the use of NDV-based live attenuated vaccine need to be recognized and addressed. Therefore, coinfection laboratory studies, including in vivo experiments, with vaccine candidate and wild-type viruses should be carried out to better evaluate the risks associated with genetic exchange.