Intranasal Powder Live Attenuated Influenza Vaccine is Thermostable, Immunogenic, and Protective Against Homologous Challenge in Ferrets

Overview

Journal NPJ Vaccines

Date 2021 Apr 22

PMID 33883559

Citations 5

Authors

Jasmina M Luczo

Tatiana Bousse

Scott K Johnson

Cheryl A Jones

Nicholas Pearce

Carlie A Neiswanger

Min-Xuan Wang

Erin A Miller

Nikolai Petrovsky

David E Wentworth

Victor Bronshtein

Mark Papania

Stephen M Tompkins

Affiliations

Soon will be listed here.

Abstract

Influenza viruses cause annual seasonal epidemics and sporadic pandemics; vaccination is the most effective countermeasure. Intranasal live attenuated influenza vaccines (LAIVs) are needle-free, mimic the natural route of infection, and elicit robust immunity. However, some LAIVs require reconstitution and cold-chain requirements restrict storage and distribution of all influenza vaccines. We generated a dry-powder, thermostable LAIV (T-LAIV) using Preservation by Vaporization technology and assessed the stability, immunogenicity, and efficacy of T-LAIV alone or combined with delta inulin adjuvant (Advax™) in ferrets. Stability assays demonstrated minimal loss of T-LAIV titer when stored at 25 °C for 1 year. Vaccination of ferrets with T-LAIV alone or with delta inulin adjuvant elicited mucosal antibody and robust serum HI responses in ferrets, and was protective against homologous challenge. These results suggest that the Preservation by Vaporization-generated dry-powder vaccines could be distributed without refrigeration and administered without reconstitution or injection. Given these significant advantages for vaccine distribution and delivery, further research is warranted.

Citing Articles

Beyond Needles: Immunomodulatory Hydrogel-Guided Vaccine Delivery Systems.

Rana M, Demirkaya C, De la Hoz Siegler H Gels. 2025; 11(1).

PMID: 39851978 PMC: 11764567. DOI: 10.3390/gels11010007.

rAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose.

Wiggins K, Winston S, Reeves I, Gaevert J, Spence Y, Brimble M J Virol. 2024; 98(8):e0078124.

PMID: 39078191 PMC: 11338075. DOI: 10.1128/jvi.00781-24.

Efficiency of Chitosan Nanocarriers in Vaccinology for Mucosal Immunization.

Gaglio S, Perduca M, Zipeto D, Bardi G Vaccines (Basel). 2023; 11(8).

PMID: 37631901 PMC: 10459455. DOI: 10.3390/vaccines11081333.

Non-Invasive Vaccines: Challenges in Formulation and Vaccine Adjuvants.

Han S, Lee P, Choi H Pharmaceutics. 2023; 15(8).

PMID: 37631328 PMC: 10458847. DOI: 10.3390/pharmaceutics15082114.

Recent Advances in Inhaled Nanoformulations of Vaccines and Therapeutics Targeting Respiratory Viral Infections.

Loo C, Lee W, Zhou Q Pharm Res. 2023; 40(5):1015-1036.

PMID: 37186073 PMC: 10129308. DOI: 10.1007/s11095-023-03520-1.

References

Gordon D, Sajkov D, Woodman R, Honda-Okubo Y, Cox M, Heinzel S . Randomized clinical trial of immunogenicity and safety of a recombinant H1N1/2009 pandemic influenza vaccine containing Advax™ polysaccharide adjuvant. Vaccine. 2012; 30(36):5407-16. PMC: 3410954. DOI: 10.1016/j.vaccine.2012.06.009. View

Kanojia G, Ten Have R, Soema P, Frijlink H, Amorij J, Kersten G . Developments in the formulation and delivery of spray dried vaccines. Hum Vaccin Immunother. 2017; 13(10):2364-2378. PMC: 5647985. DOI: 10.1080/21645515.2017.1356952. View

Wohlgemuth N, Ye Y, Fenstermacher K, Liu H, Lane A, Pekosz A . The M2 protein of live, attenuated influenza vaccine encodes a mutation that reduces replication in human nasal epithelial cells. Vaccine. 2017; 35(48 Pt B):6691-6699. PMC: 5696008. DOI: 10.1016/j.vaccine.2017.10.018. View

Taubenberger J, Morens D . 1918 Influenza: the mother of all pandemics. Emerg Infect Dis. 2006; 12(1):15-22. PMC: 3291398. DOI: 10.3201/eid1201.050979. View

Petrovsky N . Comparative Safety of Vaccine Adjuvants: A Summary of Current Evidence and Future Needs. Drug Saf. 2015; 38(11):1059-74. PMC: 4615573. DOI: 10.1007/s40264-015-0350-4. View

Gordon D, Kelley P, Heinzel S, Cooper P, Petrovsky N . Immunogenicity and safety of Advax™, a novel polysaccharide adjuvant based on delta inulin, when formulated with hepatitis B surface antigen: a randomized controlled Phase 1 study. Vaccine. 2014; 32(48):6469-77. PMC: 4253909. DOI: 10.1016/j.vaccine.2014.09.034. View

Smith T, Wu X, Ellison J, Wadhwa A, Franka R, Langham G . Assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (Urocyon cinereoargenteus). Am J Vet Res. 2017; 78(6):752-756. PMC: 5520579. DOI: 10.2460/ajvr.78.6.752. View

Honda-Okubo Y, Saade F, Petrovsky N . Advax™, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses. Vaccine. 2012; 30(36):5373-81. PMC: 3401346. DOI: 10.1016/j.vaccine.2012.06.021. View

Tregoning J, Russell R, Kinnear E . Adjuvanted influenza vaccines. Hum Vaccin Immunother. 2017; 14(3):550-564. PMC: 5861793. DOI: 10.1080/21645515.2017.1415684. View

10.

Leung V, Mapletoft J, Zhang A, Lee A, Vahedi F, Chew M . Thermal Stabilization of Viral Vaccines in Low-Cost Sugar Films. Sci Rep. 2019; 9(1):7631. PMC: 6529427. DOI: 10.1038/s41598-019-44020-w. View

11.

Foo M, Cheng Y, Su W, Donovan M . The influence of spray properties on intranasal deposition. J Aerosol Med. 2007; 20(4):495-508. DOI: 10.1089/jam.2007.0638. View

12.

Wareing M, Watson J, Brooks M, Tannock G . Immunogenic and isotype-specific responses to Russian and US cold-adapted influenza a vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice. J Med Virol. 2001; 65(1):171-7. View

13.

Erbelding E, Post D, Stemmy E, Roberts P, Augustine A, Ferguson S . A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases. J Infect Dis. 2018; 218(3):347-354. PMC: 6279170. DOI: 10.1093/infdis/jiy103. View

14.

Yen C, Hyde T, Costa A, Fernandez K, Tam J, Hugonnet S . The development of global vaccine stockpiles. Lancet Infect Dis. 2015; 15(3):340-7. PMC: 4712379. DOI: 10.1016/S1473-3099(14)70999-5. View

15.

Ferko B, Kittel C, Romanova J, Sereinig S, Katinger H, Egorov A . Live attenuated influenza virus expressing human interleukin-2 reveals increased immunogenic potential in young and aged hosts. J Virol. 2006; 80(23):11621-7. PMC: 1642586. DOI: 10.1128/JVI.01645-06. View

16.

Caspard H, Coelingh K, Mallory R, Ambrose C . Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States. Vaccine. 2016; 34(42):5066-5072. DOI: 10.1016/j.vaccine.2016.08.079. View

17.

Kilbourne E . Influenza pandemics of the 20th century. Emerg Infect Dis. 2006; 12(1):9-14. PMC: 3291411. DOI: 10.3201/eid1201.051254. View

18.

Harper S, Fukuda K, Cox N, Bridges C . Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2003; 52(RR-13):1-8. View

19.

Cox N, Subbarao K . Influenza. Lancet. 1999; 354(9186):1277-82. DOI: 10.1016/S0140-6736(99)01241-6. View

20.

Cooper P, Petrovsky N . Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 -> 1] poly(fructo-furanosyl) α-D-glucose polymers. Glycobiology. 2010; 21(5):595-606. PMC: 3106373. DOI: 10.1093/glycob/cwq201. View