Robust IgA and IgG-producing antibody forming cells in the diffuse-NALT and lungs of Sendai virus-vaccinated cotton rats associate with rapid protection against human parainfluenza virus-type 1

Abstract

Sendai virus (SeV), a natural mouse pathogen, shows considerable promise as a candidate vaccine for human parainfluenza virus-type 1 (hPIV-1), and also as a vaccine vector for other serious pathogens of infants including respiratory syncytial virus (RSV). In an effort to define correlates of immunity, we examined the virus-specific serum antibody of cotton rats inoculated intranasally (I.N.) with SeV. Virus-specific antibody forming cells (AFCs) were also measured in the bone marrow, because these are considered responsible for durable serum antibody levels in other viral systems. Results showed that a single SeV inoculation was sufficient to induce virus-specific serum antibodies and bone marrow-resident AFCs that persisted for as many as 8 months post-vaccination. Given that the predominant SeV-specific serum antibody isotype was IgG, an isotype that traffics poorly to the upper respiratory tract (URT), we asked if local nasal and lung-associated antibodies and AFCs were also present. Studies showed that: (i) SeV-specific antibodies appeared in the URT and lower respiratory tract (LRT) within 7 days after immunization, (ii) corresponding AFCs were present in the diffuse-NALT (d-NALT) and lung, (iii) AFCs in the d-NALT and lung peaked at approximately 6 weeks and persisted for the lifetime of the animal, reaching a level exceeding that of the bone marrow by an order of magnitude, (iv) IgA was the dominant isotype among AFCs in the d-NALT and lung at 4-weeks post-vaccination and thereafter, and (v) antibody and AFC responses associated with the prevention of lung infection when animals were challenged with hPIV-1 just 1 week after vaccination.