Intranasal Delivery of an RSV A2-Derived Pre-F VLP Vaccine Induces Robust Mucosal and Systemic Immunity Against RSV B...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Respiratory Syncytial Virus (RSV) causes severe respiratory illness in vulnerable populations.
• Current vaccines have limitations, necessitating novel approaches.
• Understanding RSV A2 fusion protein conformations is key for vaccine development.

Purpose of the Study:

• To evaluate the cross-protective efficacy of intranasal virus-like particles (VLPs) expressing the prefusion (pre-F) conformation of RSV A2 fusion protein.
• To assess the immune response induced by pre-F VLPs against RSV B challenge.
• To determine the safety profile of pre-F VLPs, particularly regarding vaccine-associated enhanced respiratory disease (VERD).

Main Methods:

• Intranasal administration of RSV A2-derived pre-F VLPs in a mouse model.
• Assessment of VLP reactivity against pre-F site-specific monoclonal antibodies (mAbs).
• Analysis of systemic and local immune responses, including antibody titers (IgG2a/IgG1, IgA) and cytokine production (IFN-γ).
• Histopathological examination of lung tissues to evaluate safety and disease enhancement.

Main Results:

• Pre-F VLPs showed higher reactivity against pre-F site-specific mAbs compared to formalin-inactivated RSV vaccines.
• Intranasal pre-F VLPs induced a Th1-biased immune response, characterized by a high IgG2a/IgG1 ratio and IFN-γ production.
• Significant increases in IgA levels were observed in bronchoalveolar lavage fluid and lung tissues.
• No significant lung histopathological lesions were found in pre-F VLP immunized mice, unlike in FI-RSV vaccinated mice.

Conclusions:

• Intranasal pre-F VLP immunization elicits cross-protection against RSV B.
• The vaccine candidate induces a protective Th1-skewed immune response.
• RSV A2-derived pre-F VLPs represent a potential safe and effective nasal vaccine candidate, minimizing the risk of VERD.