Evaluation of the Replication, Pathogenicity, and Immunogenicity of Avian Paramyxovirus (APMV) Serotypes 2, 3, 4, 5, 7, and 9 in Rhesus Macaques

Khattar, Sunil K.; Nayak, Baibaswata; Kim, Shin-Hee; Xiao, Sa; Samal, Sweety; Paldurai, Anandan; Buchholz, Ursula J.; Collins, Peter L.; Samal, Siba K.

We previously showed that, whereas wt APMV-2, -4, and -7 did not form syncytia or plaques in cell culture, despite their independence from added protease, in each case the introduction of the respective multi-basic site resulted in a gain-in-function conferring the ability to form syncytia and plaques [16, 18, 19] . The introduction of the multi-basic sites also increased virus replication in vitro -by 10-fold [16, 18, 19] in the case of rAPMV-2 (type 1 Africa) and rAPMV-7/Fcs-5B, and by 500-to 5000-fold in the case of rAPMV-4/Fc-BC. However, there was no observed difference in replication or pathogenicity in chickens [16, 18, 19] . For the purpose of developing APMV vaccine vectors for possible human use, these mutations had at least two potential advantages. First, the increased growth in vitro would facilitate vaccine manufacture. Second, the cleavage site mutations might increase vector replication in primates, in which case a modest increase in replication might increase the immunogenicity of an expressed foreign antigen while retaining the attenuation phenotype. In the present study, the introduction of the multi-basic sites were associated with an apparent increase in replication in the case of *This is continuation of the experiment described in Tablesô 2 and 3. Serum samples were collected before inoculation on day 0, and after inoculation on days 21 and 28.