Heterologous SARS-CoV-2 Buccal Immunization with Oral Dissolving Films Generated a Strong Systemic and Mucosal...

Area of Science:

• Vaccinology
• Immunology
• Materials Science

Background:

• Emergence of immune-evasive SARS-CoV-2 variants necessitates novel vaccination strategies.
• Heterologous vaccination may induce cross-reactive antibodies against mutating viruses.
• Oral dissolving film (ODF) offers a non-invasive vaccine delivery platform.

Purpose of the Study:

• To explore a novel heterologous vaccination strategy using microparticulate ODF formulations.
• To evaluate the immunogenicity and cross-reactivity of a prime-boost vaccine with inactivated SARS-CoV-2 variants.
• To assess the potential of this platform for inducing broad immunity.

Main Methods:

• Vaccine formulation with whole inactivated Delta and Omicron variants encapsulated in PLGA, adjuvanted with Alum.
• Heterologous prime-boost administration via ODF into the buccal cavity.
• Analysis of serum, mucosal, and tissue samples for humoral and cellular immune responses, including cross-reactivity against Alpha and Beta variants.

Main Results:

• In vitro safety and immune stimulation confirmed.
• Significant whole inactivated Delta and Omicron variant-specific antibodies and neutralizing titers observed in serum.
• Elevated secretory IgA in mucosal samples and robust CD4+, CD8a+ cellular responses in lymphoid tissues.
• Detection of IgG, IgA, and IgM antibodies in lung supernatant, indicating humoral and cellular cross-reactivity.

Conclusions:

• The microparticulate ODF vaccine platform successfully induced broad humoral and cellular immunity.
• This approach demonstrates promise for developing next-generation vaccines against SARS-CoV-2 variants.
• The non-invasive ODF delivery system is suitable for inducing mucosal and systemic immunity.