Relationships among Dissemination of Primary Parainfluenza Virus Infection in the Respiratory Tract, Mucosal and Peripheral Immune Responses, and Protection from Reinfection: a Noninvasive Bioluminescence-Imaging Study.

Respiratory paramyxoviruses such as respiratory syncytial virus (RSV) and human parainfluenza virus type 1 (HPIV1) to HPIV4 infect virtually all children by the age of 2 to 5 years, leading to partial but incomplete protection from reinfection. Here, we used luciferase-expressing reporter Sendai viruses (the murine counterpart of HPIV1) to noninvasively measure primary infection, immune responses, and protection from reinfection by either a lethal challenge or natural transmission in living mice. Both nonattenuated and attenuated reporter Sendai viruses were used, and three inoculation strategies were employed: intramuscular (i.m.), intranasal (i.n.) at a low dose and low volume, and i.n. at a high dose and high volume. High-dose, high-volume i.n. inoculation resulted in the highest levels of antibody responses and protection from reinfection. Low-dose, low-volume i.n. inoculation afforded complete protection from contact transmission and protection from morbidity, mortality, and viral growth during lethal challenge. i.m. inoculation was inferior to i.n. inoculation at inducing antibody responses and protection from challenge. For individual mice and across groups, the levels of serum binding and neutralizing antibody responses correlated with primary infection and protection from reinfection in the lungs. Contact transmission, the predominant mode of parainfluenza virus transmission, was modeled accurately by direct i.n. inoculation of Sendai virus at a low dose and low volume and was completely preventable by i.n. vaccination of an attenuated virus at a low dose and low volume. The data highlight differences in infection and protection from challenge in the upper versus lower respiratory tract and bear upon live attenuated vaccine development. [ABSTRACT FROM AUTHOR]