Intranasal Single-Replication Influenza Vector Induces Cross-Reactive Serum and Mucosal Antibodies against SARS-CoV-2...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Current SARS-CoV-2 vaccines are limited in preventing initial infection and transmission, leading to frequent breakthrough and reinfections.
• Intranasal vaccination strategies can enhance mucosal immunity, crucial for respiratory virus defense.
• Emerging SARS-CoV-2 variants necessitate improved vaccine approaches for broader protection.

Purpose of the Study:

• To develop and evaluate a novel dual vaccine candidate for simultaneous protection against SARS-CoV-2 and influenza.
• To assess the immunogenicity and cross-reactivity of the M2SR-based vaccine against SARS-CoV-2 variants and influenza A.

Main Methods:

• Development of a live intranasal M2-deficient single replication (M2SR) influenza vector expressing the SARS-CoV-2 Spike receptor binding domain (RBD).
• Intranasal vaccination of mice with the dual SARS-CoV-2 M2SR vaccine candidate.
• Measurement of serum IgG, mucosal IgA, neutralizing antibody titers, and hemagglutination inhibition (HAI) antibody titers.

Main Results:

• The dual vaccine successfully elicited high serum IgG and mucosal IgA titers against SARS-CoV-2 RBD in mice.
• Vaccinated mice developed neutralizing antibody titers against prototype and Delta SARS-CoV-2 strains, and cross-reactive antibodies against Omicron BA.4/BA.5.
• The vaccine maintained robust immune responses to influenza A, with high anti-H3 IgG and HAI titers comparable to the control vector.

Conclusions:

• The M2SR influenza viral vector expressing SARS-CoV-2 antigens demonstrates potential for a safe and effective dual vaccine.
• This intranasal vaccine candidate can induce significant mucosal and systemic immunity against both SARS-CoV-2 and influenza.
• The M2SR platform offers a promising strategy for enhanced protection against current and future respiratory viral threats.