Top

Published in:

Open Access 01-12-2023 | Influenza Virus | Research

Vaccination with recombinant Lactococcus lactis expressing HA1-IgY Fc fusion protein provides protective mucosal immunity against H9N2 avian influenza virus in chickens

Authors: Ruihua Zhang, Tong Xu, Ziping Li, Longfei Li, Chunhong Li, Xinrui Li, Zhiyue Wang, Shaohua Wang, Xuejing Wang, Hongliang Zhang

Published in: Virology Journal | Issue 1/2023

Abstract

Background

H9N2 virus is mainly transmitted through the respiratory mucosal pathway, so mucosal immunity is considered to play a good role in controlling avian influenza infection. It is commonly accepted that no adequate mucosal immunity is achieved by inactivated vaccines, which was widely used to prevent and control avian influenza virus infection. Thus, an improved vaccine to induce both mucosal immunity and systemic immunity is urgently required to control H9N2 avian influenza outbreaks in poultry farms.

Methods

In this study, we constructed a novel Lactococcus lactis (L. lactis) strain expressing a recombinant fusion protein consisting of the HA1 proteins derived from an endemic H9N2 virus strain and chicken IgY Fc fragment. We evaluated the immunogenicity and protective efficacy of this recombinant L. lactis HA1-Fc strain.

Results

Our data demonstrated that chickens immunized with L. lactis HA1-Fc strain showed significantly increased levels of serum antibodies, mucosal secretory IgA, T cell-mediated immune responses, and lymphocyte proliferation. Furthermore, following challenge with H9N2 avian influenza virus, chickens immunized with L. lactis HA1-Fc strain showed reduced the weight loss, relieved clinical symptoms, and decreased the viral titers and the pathological damage in the lung. Moreover, oropharyngeal and cloacal shedding of the H9N2 influenza virus was detected in chicken immunized with L. lactis HA1-Fc after infection, the results showed the titer was low and reduced quickly to reach undetectable levels at 7 days after infection.

Conclusion

Our data showed that the recombinant L. lactis HA1-Fc strain could induce protective mucosal and systemic immunity, and this study provides a theoretical basis for improving immune responses to prevent and control H9N2 virus infection.

Alexander DJ. Report on avian influenza in the Eastern Hemisphere during 1997–2002. Avian Dis. 2003;47(Suppl 3):792–7.PubMedCrossRef

Senne DA. Avian influenza in the Western Hemisphere including the Pacific Islands and Australia. Avian Dis. 2003;47(Suppl 3):798–805.PubMedCrossRef

Bano S, Naeem K, Malik SA. Evaluation of pathogenic potential of avian influenza virus serotype H9N2 in chickens. Avian Dis. 2003;47(Suppl 3):817–22.PubMedCrossRef

Kishida N, Sakoda Y, Eto M, Sunaga Y, Kida H. Co-infection of Staphylococcus aureus or Haemophilus paragallinarum exacerbates H9N2 influenza A virus infection in chickens. Arch Virol. 2004;11:149.

Guo YJ, Krauss S, Senne DA, Mo IP, Lo KS, Xiong XP, et al. Characterization of the pathogenicity of members of the newly established H9N2 influenza virus lineages in Asia. Virology. 2000;2:267.

Shanmuganatham K, Feeroz MM, Jones-Engel L, Smith GJ, Fourment M, Walker D, et al. Antigenic and molecular characterization of avian influenza A(H9N2) viruses, Bangladesh. Emerg Infect Dis. 2013;9:19.

Zhao G, Gu X, Lu X, Pan J, Duan Z, Zhao K, et al. Novel reassortant highly pathogenic H5N2 avian influenza viruses in poultry in China. PLoS ONE. 2012;9:7.

Gareau MG, Sherman PM, Walker WA. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol. 2010;9:7.

Bermúdez-Humarán LG. Lactococcus lactis as a live vector for mucosal delivery of therapeutic proteins. Hum Vaccin. 2009;4:5.

10.

Pouwels PH, Leer RJ, Shaw M, Heijne den Bak-Glashouwer MJ, Tielen FD, Smit E, et al. Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes. Int J Food Microbiol. 1998;2:41.

11.

Walker RI. New strategies for using mucosal vaccination to achieve more effective immunization. Vaccine. 1994;5:12.

12.

Marelli B, Perez AR, Banchio C, de Mendoza D, Magni C. Oral immunization with live Lactococcus lactis expressing rotavirus VP8 subunit induces specific immune response in mice. J Virol Methods. 2011;1:175.

13.

Dieye Y, Hoekman AJ, Clier F, Juillard V, Boot HJ, Piard JC. Ability of Lactococcus lactis to export viral capsid antigens: a crucial step for development of live vaccines. Appl Environ Microbiol. 2003;12:69.

14.

Wells JM, Mercenier A. Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria. Nat Rev Microbiol. 2008;5:6.

15.

Sha Z, Shang H, Miao Y, Huang J, Niu X, Chen R, et al. Recombinant Lactococcus Lactis expressing M1-HA2 fusion protein provides protective mucosal immunity against H9N2 Avian influenza virus in chickens. Front Vet Sci. 2020;7:153.PubMedPubMedCentralCrossRef

16.

Jefferis R. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov. 2009;3:8.

17.

Schwab I, Nimmerjahn F. Intravenous immunoglobulin therapy: How does IgG modulate the immune system? Nat Rev Immunol. 2013;3:13.

18.

Amigorena S, Bonnerot C. Fc receptors for IgG and antigen presentation on MHC class I and class II molecules. Semin Immunol. 1999;6:11.

19.

Sun H, Zhang J, Chen F, Chen X, Zhou Z, Wang H. Activation of RAW264.7 macrophages by the polysaccharide from the roots of Actinidia eriantha and its molecular mechanisms. Carbohydr Polym. 2015;121:388–402.PubMedCrossRef

20.

Dong W, Zhang H, Huang H, Zhou J, Hu L, Lian A, et al. Chicken IgY Fc linked to Bordetella avium ompA and Taishan Pinus massoniana pollen polysaccharide adjuvant enhances macrophage function and specific immune responses. Front Microbiol. 2016;7:1708.PubMedPubMedCentralCrossRef

21.

Wang H, Shan S, Wang S, Zhang H, Ma L, Hu L, et al. Fused IgY Fc and polysaccharide adjuvant enhanced the immune effect of the recombinant VP2 and VP5 subunits-a prospect for improvement of infectious Bursal disease virus subunit vaccine. Front Microbiol. 2017;8:2258.PubMedPubMedCentralCrossRef

22.

Yoshida M, Kobayashi K, Kuo TT, Bry L, Glickman JN, Claypool SM, et al. Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria. J Clin Invest. 2006;8:116.

23.

Rath T, Baker K, Pyzik M, Blumberg RS. Regulation of immune responses by the neonatal fc receptor and its therapeutic implications. Front Immunol. 2015;5:664.PubMedPubMedCentralCrossRef

24.

Rath T, Kuo TT, Baker K, Qiao SW, Kobayashi K, Yoshida M, et al. The immunologic functions of the neonatal Fc receptor for IgG. J Clin Immunol. 2013;33(Suppl 1):9–17.CrossRef

25.

Aaen KH, Anthi AK, Sandlie I, Nilsen J, Mester S, Andersen JT. The neonatal Fc receptor in mucosal immune regulation. Scand J Immunol. 2021;2:93.

26.

West AP Jr, Herr AB, Bjorkman PJ. The chicken yolk sac IgY receptor, a functional equivalent of the mammalian MHC-related Fc receptor, is a phospholipase A2 receptor homolog. Immunity. 2004;5:20.

27.

Kobayashi K, Qiao SW, Yoshida M, Baker K, Lencer WI, Blumberg RS. An FcRn-dependent role for anti-flagellin immunoglobulin G in pathogenesis of colitis in mice. Gastroenterology. 2009;5:137.

28.

Tian Z, Zhang X. Progress on research of chicken IgY antibody-FcRY receptor combination and transfer. J Recept Signal Transduct Res. 2012;5:32.

29.

Stevens J, Blixt O, Tumpey TM, Taubenberger JK, Paulson JC, Wilson IA. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science. 2006;5772:312.

30.

Chen HY, Shang YH, Yao HX, Cui BA, Zhang HY, Wang ZX, et al. Immune responses of chickens inoculated with a recombinant fowlpox vaccine coexpressing HA of H9N2 avain influenza virus and chicken IL-18. Antiviral Res. 2011;1:91.

31.

Tutykhina IL, Sedova ES, Gribova IY, Ivanova TI, Vasilev LA, Rutovskaya MV, et al. Passive immunization with a recombinant adenovirus expressing an HA (H5)-specific single-domain antibody protects mice from lethal influenza infection. Antiviral Res. 2013;3:97.

32.

Ekiert DC, Friesen RH, Bhabha G, Kwaks T, Jongeneelen M, Yu W, et al. A highly conserved neutralizing epitope on group 2 influenza A viruses. Science. 2011;6044:333.

33.

Krammer F, Pica N, Hai R, Tan GS, Palese P. Hemagglutinin stalk-reactive antibodies are boosted following sequential infection with seasonal and pandemic H1N1 influenza virus in mice. J Virol. 2012;19:86.

34.

Yang WT, Yang GL, Yang X, Shonyela SM, Zhao L, Jiang YL, et al. Recombinant Lactobacillus plantarum expressing HA2 antigen elicits protective immunity against H9N2 avian influenza virus in chickens. Appl Microbiol Biotechnol. 2017;23–24:101.

35.

Haan L, Verweij WR, Holtrop M, Brands R, van Scharrenburg GJ, Palache AM, et al. Nasal or intramuscular immunization of mice with influenza subunit antigen and the B subunit of Escherichia coli heat-labile toxin induces IgA- or IgG-mediated protective mucosal immunity. Vaccine. 2001;20–22:19.

36.

Dabaghian M, Latify AM, Tebianian M, Nili H, Ranjbar AR, Mirjalili A, et al. Vaccination with recombinant 4 × M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens. Vet Microbiol. 2014;174:1–2.CrossRef

37.

Dabaghian M, Latifi AM, Tebianian M, Dabaghian F, Ebrahimi SM. A truncated C-terminal fragment of Mycobacterium tuberculosis HSP70 enhances cell-mediated immune response and longevity of the total IgG to influenza A virus M2e protein in mice. Antiviral Res. 2015;120:23–31.PubMedCrossRef

38.

Shojadoost B, Kulkarni RR, Yitbarek A, Laursen A, Taha-Abdelaziz K, Negash Alkie T, et al. Dietary selenium supplementation enhances antiviral immunity in chickens challenged with low pathogenic avian influenza virus subtype H9N2. Vet Immunol Immunopathol. 2019;207:62–8.PubMedCrossRef

39.

Spackman E, Gelb J Jr, Preskenis LA, Ladman BS, Pope CR, Pantin-Jackwood MJ, et al. The pathogenesis of low pathogenicity H7 avian influenza viruses in chickens, ducks and turkeys. Virol J. 2010;7:331.PubMedPubMedCentralCrossRef

40.

Le Gall-Reculé G, Cherbonnel M, Pelotte N, Blanchard P, Morin Y, Jestin V. Importance of a prime-boost DNA/protein vaccination to protect chickens against low-pathogenic H7 avian influenza infection. Avian Dis. 2007;51(Suppl 1):490–4.PubMedCrossRef

41.

Zhang RH, Li PY, Xu MJ, Wang CL, Li CH, Gao JP, et al. Molecular characterization and pathogenesis of H9N2 avian influenza virus isolated from a racing pigeon. Vet Microbiol. 2020;246: 108747.PubMedCrossRef

42.

Lin YJ, Deng MC, Wu SH, Chen YL, Cheng HC, Chang CY, et al. Baculovirus-derived hemagglutinin vaccine protects chickens from lethal homologous virus H5N1 challenge. J Vet Med Sci. 2008;11:70.

43.

Qiao C, Jiang Y, Tian G, Wang X, Li C, Xin X, et al. Recombinant fowlpox virus vector-based vaccine completely protects chickens from H5N1 avian influenza virus. Antiviral Res. 2009;3:81.

44.

Pan Z, Zhang X, Geng S, Cheng N, Sun L, Liu B, et al. Priming with a DNA vaccine delivered by attenuated Salmonella typhimurium and boosting with a killed vaccine confers protection of chickens against infection with the H9 subtype of avian influenza virus. Vaccine. 2009;7:27.

45.

Oh HL, Akerström S, Shen S, Bereczky S, Karlberg H, Klingström J, Lal SK, Mirazimi A, Tan YJ. An antibody against a novel and conserved epitope in the hemagglutinin 1 subunit neutralizes numerous H5N1 influenza viruses. J Virol. 2010;16:84.

46.

Khantour AE, Houadfi ME, Nassik S, Tligui NS, Mellouli FE, Sikht FZ, Ducatez MF, Soulaymani A, Fellahi S. Protective efficacy evaluation of four inactivated commercial vaccines against low pathogenic Avian influenza H9N2 virus under experimental conditions in broiler chickens. Avian Dis. 2021;65:351–7.PubMedCrossRef

47.

Motamedi Sedeh F, Khalili I, Wijewardana V, Unger H, Shawrang P, Behgar M, Moosavi SM, Arbabi A, Hosseini SM. Improved whole gamma irradiated Avian influenza subtype H9N2 virus vaccine using trehalose and optimization of vaccination regime on broiler chicken. Front Vet Sci. 2022;9: 907369.PubMedPubMedCentralCrossRef

48.

Dabaghian M, Latify AM, Tebianian M, Nili H, Ranjbar AR, Mirjalili A, Mohammadi M, Banihashemi R, Ebrahimi SM. Vaccination with recombinant 4 × M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens. Vet Microbiol. 2014;174:116–26.PubMedCrossRef

49.

Gan L, Tian Y, Zhao Y, Shan XQ, Zhou W, Xia BB, Chen J, Wang ML, Zhao J. Enhancing immunogenicity and protective efficacy of inactivated avian influenza H9N2vaccine with recombinant chicken IFN-α in chicken. Vet Microbiol. 2019;234:77–82.PubMedCrossRef

50.

Rahman MM, Uyangaa E, Han YW, Kim SB, Kim JH, Choi JY, Eo SK. Enhancement of Th1-biased protective immunity against avian influenza H9N2 virus via oral co-administration of attenuated Salmonella enterica serovar Typhimurium expressing chicken interferon-α and interleukin-18 along with an inactivated vaccine. BMC Vet Res. 2012;8:105.PubMedPubMedCentralCrossRef

51.

Park JK, Lee DH, Cho CH, Yuk SS, To EO, Kwon JH, Noh JY, Kim BY, Choi SW, Shim BS, Song MK, Lee JB, Park SY, Choi IS, Song CS. Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection. Vet Microbiol. 2014;169:211–7.PubMedCrossRef

52.

Bortolami A, Mazzetto E, Kangethe RT, Wijewardana V, Barbato M, Porfiri L, Maniero S, Mazzacan E, Budai J, Marciano S, Panzarin V, Terregino C, Bonfante F, Cattoli G. Protective efficacy of H9N2 Avian influenza vaccines inactivated by ionizing radiation methods administered by the parenteral or mucosal routes. Front Vet Sci. 2022;9: 916108.PubMedPubMedCentralCrossRef

Title: Vaccination with recombinant Lactococcus lactis expressing HA1-IgY Fc fusion protein provides protective mucosal immunity against H9N2 avian influenza virus in chickens
Authors: Ruihua Zhang
Tong Xu
Ziping Li
Longfei Li
Chunhong Li
Xinrui Li
Zhiyue Wang
Shaohua Wang
Xuejing Wang
Hongliang Zhang
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Influenza Virus
Vaccination
Influenza
Published in: Virology Journal / Issue 1/2023
Electronic ISSN: 1743-422X
DOI: https://doi.org/10.1186/s12985-023-02044-9

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Vaccination with recombinant Lactococcus lactis expressing HA1-IgY Fc fusion protein provides protective mucosal immunity against H9N2 avian influenza virus in chickens

Abstract

Background

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2023

Targeting the conserved coronavirus octamer motif GGAAGAGC is a strategy for the development of coronavirus vaccine

Viral etiologies of lower respiratory tract infections in children < 5 years of age in Addis Ababa, Ethiopia: a prospective case–control study

A comparison of transmissibility of SARS-CoV-2 variants of concern

Untargeted metabolomics of the intestinal tract of DEV-infected ducks

Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation

Patch-clamp studies and cell viability assays suggest a distinct site for viroporin inhibitors on the E protein of SARS-CoV-2

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page