Immunogenicity and protective efficacy of prime-boost immunization in mice vaccinated with live and inactivated influenza A (H5N1) vaccines

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Abstract

Avian influenza A (H1N1) in humans is characterized by severe clinical manifestation and high mortality. The main drawback of current human H5N1 vaccines is related to low immunogenicity. Prime-boost vaccination is considered as an effective approach to enhance vaccine immunogenicity. The aim of this study was to compare immune response and protective efficacy of diverse prime-boost immunization protocols: 1) prime and boost with live influenza vaccine (LAIV) А/17/Turkey/Turkey/05/133 (H5N2); 2) prime with LAIV А/17/Turkey/Turkey/05/133 (H5N2) followed by boost with inactivated influenza vaccine (IIV) “Orniflu” (H5N1). Both vaccination protocols were found to increase serum antibody level against homologous and heterologous influenza A virus strains. In particular, serum HAI antibodies were significantly elevated solely after LAIV/LAIV vaccination. A more sensitive sandwich ELISA assay revealed that serum virus-specific IgG antibody levels were significantly increased after both vaccination protocols as well as after a single LAIV or IIV vaccination. Both LAIV and IIV boost increased titers of serum IgG specific against unrelated influenza A (H5N1) strains: homologous A/NIBRG-23 (clade 2.2), A/Indonesia (clade 2.1) and, to a lesser extent, against clade 1 virus A/ Vietnam and even against heterologous А/New York (H1N1). Single LAIV vaccination was also able to induce antibody responses against all strains examined, though to a lesser degree as compared with either prime-boost protocols. However, amount of splenic CD8+  Тcells specific to homologous influenza A virus strain was solely observed after LAIV/IIV vaccination. Moreover, both LAIV and IIV boosting effect demonstrated high protection level against lethal challenge with А (H1N1) WT virus and significantly decreased lung viral titer compared to control group. Furthermore, both regimens resulted in lung virus clearance after non-lethal challenge with clade 1, 2.1 or 2.2 influenza А (H5N1). In conclusion, we demonstrated that both LAIV/LAIV and LAIV/IIV regimens were able to induce cross-clade A (H5N1) response and that prime-boost immunization was a promising approach to improve immunogenicity of influenza A (H5N1) virus vaccine.

About the authors

I. Losev

Institute of Experimental Medicine

Email: iemlosev@gmail.com
ORCID iD: 0000-0002-5245-7315

Losev Igor. V. - Researcher, Laboratory of Immunology and Viral Disease Prevention, Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Russian Federation

G. Petukhova

Institute of Experimental Medicine

Email: gala.iem@gmail.com
ORCID iD: 0000-0001-9312-4739

Petukhova Galina D. - PhD (Biology), Senior Researcher, Laboratory of Immunology and Viral Disease Prevention, Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Phone: +7 (921) 759-96-06 (mobile).

Russian Federation

I. Isakova-Sivak

Institute of Experimental Medicine

Email: isakova.sivak@gmail.com
ORCID iD: 0000-0002-2801-1508

Isakova-Sivak Irina N. - PhD (Biology), Head of the Laboratory of Immunology and Viral Disease Prevention, Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Russian Federation

L. Rudenko

Institute of Experimental Medicine

Author for correspondence.
Email: vacine@mail.ru
ORCID iD: 0000-0002-0107-9959

Rudenko Larisa G. - PhD, MD (Biology), Honored Worker of Science of the Russian Federation, Head of the Department of Virology, Institute of Experimental Medicine.

197376, St. Petersburg, Academic Pavlov str., 12.

Russian Federation

References

  1. Сергеева М.В., Крохин А., Матросович М., Матросович Т., Волшек М., Киселев О.И., Романова Ю.Р. Влияние конформационной стабильности гемагглютинина вируса гриппа на качество инактивированных вакцин H5N1 // Microbiology Independent Research Journal. 2014. Т. 1, № 1. С. 1–11. [Sergeeva M., Krokhin A., Matrosovich M., Matrosovich T., Wolschek M., Kiselev O., Romanova J. H5N1 inf luenza vaccine quality is affected by hemagglutinin conformational stability. Microbiology Independent Research Journal, 2014, vol. 1, no. 1, pp. 1–11. (In Russ.)]
  2. Baz M., Luke C.J., Cheng X., Jin H., Subbarao K. H5N1 vaccines in humans. Virus Res., 2013, vol. 178, iss. 1, pp. 78–98.
  3. Brooks W.A., Zaman K., Lewis K.D., Ortiz J. R., Goswami D., Feser J., Sharmeen A.T., Nahar R., Rahman M., Rahman M.Z., Barin B., Yunus M., Fry A.M., Bresee J., Azim T., Kathleen K.M. Efficacy of a Russian-backbone live attenuated inf l uenza vaccine among young children in Bangladesh: a randomised, double-blind, placebo-controlled trial. Lancet Glob. Health, 2016, vol. 4: e946–e954.
  4. Caspard H., Heikkinen T., Belshe R.B., Ambrose C.S. A systematic review of the efficacy of live attenuated inf luenza vaccine upon revaccination of children. Hum. Vacc. Immunother., 2016, vol. 12, no. 7, pp. 1721–1727.
  5. Cottey R., Rowe C.A., Bender B.S. Inf luenza virus. Curr. Protoc. Immunol., 2001, chapter 19: unit 19.11. doi: 10.1002/0471142735.im1911s42
  6. Cumulative number of confirmed human cases for avian inf luenza A(H5N1) reported to WHO, 2003-2015. URL: http://www.who.int/influenza/human_animal_interface/EN_GIP_201503031cumulativeNumberH5N1cases.pdf
  7. Ebensen T., Debarry J., Pedersen G.K., Blazejewska P., Weissmann S., Schulze K., McCullough K.C., Cox R.J., Guzmán C.A. Mucosal administration of cycle-di-nucleotide-adjuvanted virosomes efficiently induces protection against inf luenza H5N1 in mice. Front. Immun., 2017, vol. 8: 1223.
  8. Foster B., Prussan C. Detection of intracellular cytokines by f low cytometry. Curr. Protoc. Immunol., 2007, chapter 6: unit 6.24. doi: 10.1002/0471142735.im0624s78
  9. Friede M., Palkonyay L., Alfonso C., Pervikov Y., Torelli G., Wood D., Kieny M.P. WHO initiative to increase global and equitable access to inf luenza vaccine in the event of a pandemic: supporting developing country production. Vaccine, 2011, suppl. 29: A2–A7. doi: 10.1016/j.vaccine.2011.02.079
  10. Goji N.A., Nolan C., Hill H., Wolff M., Noah D.L., Williams T.B., Rowe T., Treanor J.J. Immune responses of healthy subjects to a single dose of intramuscular inactivated inf luenza A/ Vietnam/1203/2004 (H5N1) vaccine after priming with an antigenic variant. J. Infect. Dis., 2008, vol. 198, iss. 5, pp. 635–641.
  11. Houser K., Subbarao K. Inf luenza vaccines: challenges and solutions. Cell Host Microbe, 2015, vol. 17, no. 3, pp. 295–300.
  12. Ikeno D., Kimachi K., Kudo Y., Goto S., Itamura S., Odagiri T., Tashiroc M. Kino Y. A prime-boost vaccination of mice with heterologous H5N1 strains. Vaccine, 2009, vol. 27, iss. 23, pp. 3121–3125.
  13. Matsuoka Y., Lamirande E.W., Subbarao K. Mouse model for Inf luenza. Curr. Protoc. Microbiol., 2009, chapter 15: unit 15G.3. doi: 10.1002/9780471729259.mc15g03s13
  14. Nayak J.L., Richards K.A., Yang H., Treanor J.J., Sant A.J. Effect of inf luenza A(H5N1) vaccine prepandemic priming on CD4+ T-cell response. J. Infec. Dis., 2015, vol. 211, iss. 9, pp. 1408–1417.
  15. Peng Y., Wang B., Talaat K., Karron R., Powell T. J., Zeng H., Dong D., Luke C.J., McMichael A., Subbarao K., Dong T. Boosted inf luenza-specific T cell responses after H5N1 pandemic live attenuated inf luenza virus vaccination. Front. Immunol., 2015, vol. 6: 287.
  16. Pitisuttithum P., Boonnak K., Chamnanchanunt S., Puthavathana P., Luvira V., Lerdsamran H., Kaewkungwal J., Lawpoolsri S., Thanachartwet V., Silachamroon U., Masamae W., Schuetz A., Wirachwong P., Thirapakpoomanunt S., Rudenko L., Sparrow E., Friede M., Kieny M.P. Safety and immunogenicity of a live attenuated inf luenza H5 candidate vaccine strain A/17/Turkey/ Turkey/05/133 H5N2 and its priming effects for potential pre-pandemic use: a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis., 2017, vol. 17, iss. 8, pp. 833–842.
  17. Rudenko L., Kiseleva I., Stukova M., Erofeeva M., Naykhin A., Donina S., Larionova N., Pisareva M., Krivitskaya V., Flores J; Russian LAIV Trial Study Group. Clinical testing of pre-pandemic live attenuated A/H5N2 inf luenza candidate vaccine in adult volunteers: results from a placebo-controlled, randomized double-blind phase I study. Vaccine, 2015, vol. 33, iss. 39, pp. 5110 –5117.
  18. Rudenko L., Naykhin A., Donina S., Korenkov D., Petukhova G., Isakova-Sivak I., Losev I., Stukova M., Erofeeva M., Nikiforova A., Power M., Flores J. Assessment of immune responses to H5N1 inactivated inf luenza vaccine among individuals previously primed with H5N2 live attenuated inf luenza vaccine. Hum. Vaccin. Immunother., 2015, vol. 11, no. 12, pp. 2839–2848.
  19. Rudenko L., Yeolekar L., Kiseleva I., Isakova-Sivak I. Development and approval of live attenuated inf luenza vaccines based on Russian master donor viruses: process challenges and success stories. Vaccine, 2016, vol. 34, no. 45, pp. 5436–5441.
  20. Sabarth N., Howard M.K., Savidis-Dacho H., van Maurik A., Barrett P.N., Kistner O. Comparison of single, homologous primeboost and heterologous prime-boost immunization strategies against H5N1 inf luenza virus in a mouse challenge model. Vaccine, 2010, vol. 28, pp. 650 –656.
  21. Stephenson I., Nicholson K.G., Colegate A., Podda A., Wood J., Ypma E., Zambon M. Boosting immunity to inf luenza H5N1 with MF59-adjuvanted H5N3 A/Duck/Singapore/97 vaccine in a primed human population. Vaccine, 2003, vol. 21, no. 15, pp. 1687–1693.
  22. Wang Z., Loh L., Kedzierski L., Kedzierska K. Avian inf luenza viruses, inf lammation, and CD8+ T Cell immunity. Front. Immunol., 2016, vol. 7: 60.
  23. WHO. Inf luenza (Seasonal). 2016. URL: http://www.who.int/mediacentre/factsheets/fs211/en (04.12.2017)

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Copyright (c) 2019 Losev I., Petukhova G., Isakova-Sivak I., Rudenko L.

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