Biology subjects

Kalange, D.

Publications and source records attributed to Kalange, D..

2 recordsLinked to original sources

bioRxiv2026

Intranasal immunization with live-attenuated RSV-vectored SARS-CoV-2 vaccines elicits antigen-specific systemic and mucosal immunity and protects against viral challenge and natural infection

The emergence of new SARS-CoV-2 variants and breakthrough infections underscores the need for next-generation vaccines capable of protecting from natural infection and/or preventing virus transmission to others. Intranasal vaccination offers a promising approach by eliciting local immune responses in the nasal mucosa, the primary site of infection and reservoir for transmissible virus. We evaluated two live-attenuated, respiratory syncytial virus vectored vaccines in which the RSV F and G surface glycoproteins were replaced with a chimeric SARS-CoV-2 Spike protein from either the ancestral USA/WA-1/2020 strain (MV-014-212) or the Delta variant (MV-014-212-delta). A single intranasal dose of either vaccine elicited systemic and mucosal immunity in K18-hACE2 mice, including serum neutralizing antibodies, Spike-specific memory B cells and plasmablasts, and Spike-specific CD8 lung-resident memory T cells. Although MV-014-212-delta vaccination provided the best protection against Delta variant virus challenge, both vaccines decreased viral loads in nasal discharge, lung and brain, and reduced weight loss and mortality. In naturally acquired infection studies, vaccinated hamsters exposed to infected cagemates exhibited minimal weight loss, limited viral replication within the nasal mucosa, and attenuated lung pathology. Therefore, intranasal RSV-vectored vaccines can elicit broad protective respiratory immunity, suggesting that this platform could be leveraged for other respiratory pathogens.

immunology↗

bioRxiv2025

Mucosal delivery of influenza antigens using a replication deficient adenovirus supports broadly reactive antibody responses and heterologous viral immunity in the respiratory tract of animals

Systemically administered influenza vaccines provide strain-limited protection, while influenza infection of the respiratory epithelium supports development of lung resident memory B and T cells and more broadly reactive antibody responses. To test whether local antigen delivery is critical for establishing broad immunity, we directly compared respiratory tract and systemic delivery of influenza antigens to mice and hamsters using a replication-deficient adenovirus serotype 5 vector (Ad5[E1-,E2b-,E3-]). Both immunization routes elicited antibody responses in the lower respiratory tract and antigen-specific B and T cells in the draining lymph node. However, only intranasal immunization established lung-resident memory B and T cells, induced IgA responses in the upper respiratory tract directly at the site of viral entry and supported generation of IgA and IgG antibodies that bound antigenically drifted and distantly related influenza strains, including those of avian origin. Intranasal immunization accelerated viral clearance following heterologous virus challenge and was associated with limited pulmonary inflammation and fibrosis. Thus, intranasal immunization with the immunologically stealthy Ad5[E1-,E2b-,E3-] platform supports respiratory and systemic immunity to divergent influenza strains in the absence of overt lung immunopathology, suggesting that local antigen delivery may be key to development of more broadly protective "universal" flu vaccines.

immunology↗