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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity

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Published on: June 25, 2015

Paradoxical modulation of influenza by intranasal administration of non-replicating adenovirus particles

De-Chu Christopher Tang¹

¹VaxDome Inc., Commercialization Program, University of North Texas Health Science Center, Fort Worth, Texas, United States of America.

|November 12, 2020

Abstract:

Respiratory mucosal infection by airborne microbes is a common event that occurs every day. We report here that intranasal administration of non-replicating adenovirus (Ad) particles to mice could either confer rapid protection against influenza virus (IFV) challenge independent of adaptive immunity, or exacerbate influenza by triggering rapid death. The life-or-death outcome hinges on the time interval between Ad administration and IFV challenge in conjunction with specific mouse/IFV strains. Intranasal instillation of Ad particles 1-47 days prior to IFV challenge conferred rapid protection against influenza in Balb/c mice whereas exposure to Ad 39 days prior to challenge with a specific IFV strain or 1 day post-challenge with that IFV strain induced rapid death in C57BL/6 mice. Notably, consecutive administrations of Ad prior to IFV challenge conferred a synergy in triggering a potent anti-influenza state; even a detrimental Ad exposure 39 days before challenge with the deadly IFV strain was reversed to a beneficial one by subsequent Ad boosts. Results revealed an intricate relationship between infection and innate immunity that is a linchpin around which effects revolve from protective immunity to collateral damage. It is urgent to repeat the experiments with an expanded scope for characterizing the status that defines susceptibility or resistance to IFV infection and subsequently reveal the underlying mechanisms. Whether broad heterologous protective effects induced by AdE and adaptive immunity elicited by vaccination could confer synergy during mitigation of a pandemic remains to be seen.

Insights

Intranasal adenovirus particles can protect against or worsen influenza virus infection in mice. The outcome depends on timing, mouse strain, and adenovirus boosts, highlighting the complex role of innate immunity.

Area of Science:

Immunology
Virology
Infectious Diseases

Background:

Respiratory mucosal infections by airborne microbes are frequent.
Adenovirus (Ad) particles administered intranasally can influence influenza virus (IFV) infection outcomes.
The interaction between Ad and host innate immunity is critical in determining protection or exacerbation.

Purpose of the Study:

To investigate the dual role of intranasal non-replicating adenovirus particles in influenza virus infection.
To determine how the timing of Ad administration and specific host factors influence IFV challenge outcomes.
To explore the potential for synergistic effects of Ad administration and vaccination in mitigating influenza.

Main Methods:

Intranasal administration of non-replicating adenovirus particles to different mouse strains (Balb/c, C57BL/6).
Challenge with influenza virus at various time points before and after Ad administration.
Evaluation of protection or exacerbation of IFV infection, including survival rates.

Main Results:

Intranasal Ad administration 1-47 days prior to IFV challenge conferred rapid protection in Balb/c mice.
Ad exposure 39 days before or 1 day after IFV challenge induced rapid death in C57BL/6 mice.
Consecutive Ad administrations demonstrated synergy, reversing detrimental effects and enhancing protection.

Conclusions:

The outcome of IFV infection following Ad administration is highly dependent on the timing of exposure, mouse strain, and Ad boost strategy.
Adenovirus particles can modulate innate immunity to either protect against or exacerbate IFV infection.
Further research is needed to fully characterize the mechanisms underlying these differential effects and their potential clinical applications.

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