What Are the Risks—Hypothetical and Observed—of Recombination Involving Live Vaccines and Vaccine Vectors Based on Nonsegmented Negative-Strain RNA Viruses?

Abstract

Newcastle disease virus (NDV) is a nonsegmented negative-strand RNA virus (NNSV) that is being developed as a potential vaccine vector for use in poultry (7, 12, 17) and humans (5, 6). The primary proposed human use would be to express protective antigens of highly pathogenic agents for outbreak control. We noted (1) that one of the advantages of NDV is that “gene exchange seems to be rare for nonsegmented negative strand RNA viruses, with few reported instances. This differs to the frequent gene reassortment observed for segmented viruses, such as influenza virus and rotavirus, and the high frequency of recombination observed for certain viruses, such as coronavirus and poliovirus.” In a recent letter to the editor (9), Han et al. criticized our studies, suggesting that we (i) dismissed the possibility of recombination, (ii) failed to recognize the potentially adverse consequences of recombination, and (iii) did not experimentally address the potential for the instability of the inserted foreign gene.