Enhancing Immunity with Intranasal Influenza Vaccine Nanoparticles

Benefits of Intranasal Vaccination for Influenza

Intranasal vaccination offers several advantages over traditional IM injections. The most significant benefit is the ability to induce both systemic and localized mucosal immunity, which is crucial for effective protection against respiratory pathogens such as influenza. Mucosal immunity is primarily mediated by secretory immunoglobulin A (IgA), which plays a critical role in neutralizing pathogens at mucosal surfaces before they can establish an infection. Studies have shown that intranasal administration of vaccines can lead to higher levels of IgA compared to IM administration, providing a robust first line of defense against influenza viruses (Park et al., 2025).

Moreover, intranasal vaccination can enhance patient compliance, particularly among children and individuals with needle phobia. The non-invasive nature of nasal delivery reduces the discomfort associated with needle injections, potentially leading to higher vaccination rates in populations that are typically hesitant to receive vaccines.

In addition to improving compliance, intranasal vaccines can also stimulate a broad range of immune responses. The local immune environment of the nasal mucosa is rich in antigen-presenting cells (APCs), which play a pivotal role in initiating adaptive immune responses. This localized activation can lead to a more effective and rapid immune response upon exposure to the influenza virus.

Formulation of Layer-by-Layer Influenza Vaccine Nanoparticles

The formulation of influenza vaccine nanoparticles using a layer-by-layer technique represents a significant advancement in vaccine delivery systems. This method involves the sequential deposition of biocompatible materials, allowing the creation of a stable nanoparticle core that can encapsulate antigens and adjuvants. The core is typically composed of antigens such as the hemagglutinin (HA) and M2e proteins, which are essential for eliciting immune responses.

The LBL technique allows for the coating of nanoparticles with alternating layers of mucoadhesive and muco-inert materials. For instance, cationic chitosan can be used as a mucoadhesive layer, enhancing the retention of the nanoparticles within the nasal cavity and facilitating prolonged contact with mucosal immune cells. Conversely, anionic adjuvants, such as CpG, can be incorporated to stimulate a robust immune response without eliciting excessive inflammation (Park et al., 2025).

This innovative formulation strategy not only improves the stability and bioavailability of the vaccine but also enhances the overall immunogenicity of the delivered antigens. The combination of mucoadhesive and muco-inert properties allows for a controlled release of the antigens, promoting sustained immune activation.

Role of Mucoadhesive and Muco-Inert Coatings in Delivery

The dual coating of nanoparticles with mucoadhesive and muco-inert materials plays a crucial role in enhancing the effectiveness of intranasal vaccines. Mucoadhesive coatings, such as chitosan, facilitate the retention of nanoparticles on the mucosal surface, allowing for prolonged exposure to the immune system. This increased retention time enhances antigen uptake by APCs, leading to improved immune activation.

On the other hand, muco-inert coatings prevent the rapid clearance of nanoparticles from the nasal cavity, ensuring that the vaccine remains available for prolonged interactions with local immune cells. This strategic combination optimizes the delivery of the vaccine, allowing for a more effective immune response.

Furthermore, the use of mucoadhesive materials can also enhance the stability of the nanoparticles, protecting the encapsulated antigens from degradation within the nasal cavity. This stability is essential for maintaining the efficacy of the vaccine and ensuring that the immune system can effectively recognize and respond to the antigens.

Immune Response Comparison: Intranasal vs. Intramuscular Vaccination

Comparative studies have demonstrated significant differences in immune responses elicited by intranasal versus intramuscular vaccination. Intranasal vaccines have been shown to induce higher levels of mucosal IgA compared to IM vaccines, which primarily stimulate systemic IgG responses. This difference is critical, as mucosal IgA plays a vital role in neutralizing pathogens at the entry point of infection, thereby preventing viral replication and dissemination.

In addition to IgA, intranasal vaccination has been associated with a more diverse immune response, including the activation of various T-cell subsets. Research indicates that intranasal administration can lead to a higher proportion of activated CD4+ and CD8+ T cells in the respiratory mucosa, which are essential for mounting an effective cellular immune response against influenza infections (Park et al., 2025).

Moreover, the effectiveness of intranasal vaccines in eliciting immune responses has been corroborated by studies showing improved protection against subsequent influenza challenges. For instance, animals vaccinated intranasally with LBL influenza vaccine nanoparticles demonstrated significantly reduced viral titers upon challenge compared to those receiving IM vaccinations, indicating the superior efficacy of the intranasal route for this type of vaccine.

Efficacy of Nanoparticle Vaccines Against Influenza Challenges

The efficacy of LBL influenza vaccine nanoparticles has been evaluated in various preclinical models, demonstrating their potential for robust immune activation and protection against influenza virus challenges. The studies indicate that intranasal administration of these nanoparticles leads to significant reductions in viral loads and improved survival rates following exposure to influenza strains.

In a comparative efficacy study, mice vaccinated with LBL nanoparticles exhibited heightened immune responses, including elevated IgA titers and increased activation of T-cell populations, compared to those receiving conventional IM vaccines. The enhanced immune profile translated into better protection against viral replication, highlighting the potential of nanoparticle-based intranasal vaccines in providing a dual mechanism of action—stimulating both mucosal and systemic immunity.

Furthermore, the durability of the immune response elicited by nanoparticle vaccines appears to be superior, with studies reporting sustained antibody levels and long-lasting T-cell memory. This long-term immunity is vital for effective protection in a population exposed to circulating influenza viruses, particularly in light of the rapid antigenic drift associated with these pathogens.

Conclusion

The advent of intranasal influenza vaccines formulated as LBL nanoparticles represents a promising advancement in the quest for more effective vaccination strategies against influenza. By enhancing mucosal immunity and providing a durable immune response, these nanoparticle vaccines have the potential to improve public health outcomes significantly. As research continues to elucidate their mechanisms of action, the integration of such innovative vaccine delivery systems may reshape our approach to combating influenza and other respiratory pathogens.

References

1. Park, J., Pho, T., Bhatnagar, N., Mai, L. D., Rodriguez-Otero, M. R., Pal, S. S., Le, C. T. T., Jenison, S. E., Li, C., May, G. A., Arioka, M., & Kang, S.-M. (2025). Multilayer Adjuvanted Influenza Protein Nanoparticles Improve Intranasal Delivery and Antigen-Specific Immunity. ACS Nano

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FAQ

What are the main benefits of intranasal vaccination for influenza?

Intranasal vaccination enhances both systemic and mucosal immunity, reduces discomfort associated with needles, and potentially increases vaccination rates.

How do layer-by-layer nanoparticles improve vaccine delivery?

Layer-by-layer nanoparticles enhance stability, bioavailability, and retention time within the nasal cavity, promoting sustained immune activation.

What immune responses are elicited by intranasal vaccines compared to intramuscular?

Intranasal vaccines generally induce higher levels of mucosal IgA and activate more diverse T-cell populations than intramuscular vaccines.

How effective are nanoparticle vaccines against influenza?

Nanoparticle vaccines have shown significant efficacy in preclinical studies, with reduced viral loads and improved survival rates in vaccinated animals.

What is the significance of mucosal immunity?

Mucosal immunity provides a critical first line of defense against pathogens at their entry points, helping to neutralize them before they can cause infection.