Immunopotentiators Improve the Efficacy of Oil-Emulsion-Inactivated Avian Influenza Vaccine in Chickens, Ducks and Geese

Lu, Jihu; Wu, Peipei; Zhang, Xuehua; Feng, Lei; Dong, Bin; Chen, Xuan; Liu, Xiufan; Peng, Daxin; Liu, Yuan; Ma, Huailiang; Hou, Jingbo; Tang, Yinghua

doi:10.1371/journal.pone.0156573

Cited by 7 publications

(14 citation statements)

References 29 publications

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“…In the efficacy study, we have detected that the monovalent vaccine combination use with CVCVA5, up regulation of IFNγ and IL-4 levels in serum, and mucosal antibodies in tears and BAL, which are also consistent with our previous study with H5 or H9 vaccine mixing use with CVCVA5 (Tang et al, 2014;Lu et al, 2016). Rising cytokine levels and mucosal immunity may provide some clues to the CVCCVA5 improving the efficacy of vaccine, including vaccine-or antigen-sparing tests, and the sterile immunity test with ND and IBD vaccination.…”

Section: Discussionsupporting

confidence: 89%

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Feng

et al. 2017

Front. Microbiol.

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We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND), Egg Drop Syndrome virus (EDS), Infectious Bronchitis virus (IB), and Infectious Bursal Disease virus (IBD). The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9). A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the CVCVA5 improved the serum and mucosal antibody levels, cytokine levels of the chickens given the univalent vaccine, and also improved serum antibody titers in bivalent and tetravalent vaccines. This has a potential as an improve vaccine.

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Section: Discussionsupporting

confidence: 89%

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Feng

et al. 2017

Front. Microbiol.

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“…9C). Many previous studies reported that even though a vaccine is able to provide protection from mortality, immunized animals generally shed virus for up to 3 days after virus challenge (44)(45)(46). In agreement with data from those studies, the heterologous H5N2 and H5N8 viruses were detected until 5 dpi, but the virus detection periods and viral titers were significantly reduced (at least 10 times) compared to those of the H9N2 vaccine group (P Ͻ 0.05) ( Table 2).…”

Section: Discussionsupporting

confidence: 86%

Vaccine Efficacy of Inactivated, Chimeric Hemagglutinin H9/H5N2 Avian Influenza Virus and Its Suitability for the Marker Vaccine Strategy

Kim

Park

et al. 2017

J Virol

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In order to produce a dually effective vaccine against H9 and H5 avian influenza viruses that aligns with the DIVA (differentiating infected from vaccinated animals) strategy, we generated a chimeric H9/H5N2 recombinant vaccine that expressed the whole HA1 region of A/CK/Korea/04163/04 (H9N2) and the HA2 region of recent highly pathogenic avian influenza (HPAI) A/MD/Korea/W452/14 (H5N8) viruses. The chimeric H9/H5N2 virus showed in vitro and in vivo growth properties and virulence that were similar to those of the low-pathogenic avian influenza (LPAI) H9 virus. An inactivated vaccine based on this chimeric virus induced serum neutralizing (SN) antibodies against both H9 and H5 viruses but induced cross-reactive hemagglutination inhibition (HI) antibody only against H9 viruses. Thus, this suggests its compatibility for use in the DIVA strategy against H5 strains. Furthermore, the chimeric H9/H5N2 recombinant vaccine protected immunized chickens against lethal challenge by HPAI H5N8 viruses and significantly attenuated virus shedding after infection by both H9N2 and HPAI H5N8 viruses. In mice, serological analyses confirmed that HA1-and HA2 stalk-specific antibody responses were induced by vaccination and that the DIVA principle could be employed through the use of an HI assay against H5 viruses. Furthermore, each HA1-and HA2 stalk-specific antibody response was sufficient to inhibit viral replication and protect the chimeric virusimmunized mice from lethal challenge with both mouse-adapted H9N2 and wild-type HPAI H5N1 viruses, although differences in vaccine efficacy against a homologous H9 virus (HA1 head domain immune-mediated protection) and a heterosubtypic H5 virus (HA2 stalk domain immune-mediated protection) were observed. Taken together, these results demonstrate that the novel chimeric H9/H5N2 recombinant virus is a lowpathogenic virus, and this chimeric vaccine is suitable for a DIVA vaccine with broadspectrum neutralizing antibody against H5 avian influenza viruses. IMPORTANCE Current influenza virus killed vaccines predominantly induce antihemagglutinin (anti-HA) antibodies that are commonly strain specific in that the antibodies have potent neutralizing activity against homologous strains but do not crossreact with HAs of other influenza virus subtypes. In contrast, the HA2 stalk domain is relatively well conserved among subtypes, and recently, broadly neutralizing antibodies against this domain have been isolated. Therefore, in light of the need for a vaccine strain that applies the DIVA strategy utilizing an HI assay and induces broad cross-protection against H5N1 and H9N2 viruses, we generated a novel chimeric H9/ H5N1 virus that expresses the entire HA1 portion from the H9N2 virus and the HA2 region of the heterosubtypic H5N8 virus. The chimeric H9/H5N2 recombinant vaccine protected immunized hosts against lethal challenge with H9N2 and HPAI H5N1

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“…Chickens from each test group were randomly selected and intranasal challenged with 100 LD 50 (0.1 ml) H5 wild-type influenza viruses (ZJ and DT) at 3 weeks PV. These challenge viruses were derived from the clade of 2.3.4.6 (A/Chicken/Zhejiang/201, ZJ, H5N2, n = 10 in each challenge group) and clade 7 (A/Chicken/Huadong/4/2008, DT, H5N1, n = 10 in each challenge group) ( 19 ). Chickens were monitored and recorded clinical signs and body weights for 14 days post challenge (PC).…”

Section: Methodsmentioning

confidence: 99%

“…Serum antibody levels were titrated by hemagglutinin inhibition (HI) assay or serum-neutralization (SN) assay in DF-1 cell (ATCC, CRL-12203) ( 19 , 22 ). The SN assay was performed as following described.…”

Section: Methodsmentioning

confidence: 99%

“…The chicken cytokine levels of IFN-γ (Invitrogen, CA, USA) and IL-4 (USCN, Wuhan, China) in sera at 2 and 3 weeks PV were measured by commercially available ELISA kits following the manufacturer’s instructions as described in our previous reports ( 19 , 20 ). The mucosal antibodies from bronchoalveolar lavage fluids (BAL) were determined by an HI assay.…”

Section: Methodsmentioning

confidence: 99%

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Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

Zhang

et al. 2017

Front. Immunol.

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The H5 subtype highly pathogenic avian influenza (HPAI) virus is one of the greatest threats to global poultry industry. To develop broadly protective H5 subunit vaccine, a recombinant consensus HA sequence (rHA) was constructed and expressed in virus-like particles (rHA VLPs) in the baculovirus-insect cell system. The efficacy of the rHA VLPs vaccine with or without immunopotentiator (CVCVA5) was assessed in chickens. Compared to the commercial Re6 or Re6-CVCVA5 vaccines, single dose immunization of chickens with rHA VLPs or rHA-CVCVA5 vaccines induced higher levels of serum hemagglutinin inhibition titers and neutralization titers, mucosal antibodies, IFN-γ and IL-4 cytokines in sera, and cytotoxic T lymphocyte responses. The rHA VLPs vaccine was superior to the commercial Re6 vaccine in conferring cross-protection against different clades of H5 subtype viruses. This study reports that H5 subtype consensus HA VLP single dose vaccination provides broad protection against HPAI virus in chickens.

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Immunopotentiators Improve the Efficacy of Oil-Emulsion-Inactivated Avian Influenza Vaccine in Chickens, Ducks and Geese

Cited by 7 publications

References 29 publications

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

Vaccine Efficacy of Inactivated, Chimeric Hemagglutinin H9/H5N2 Avian Influenza Virus and Its Suitability for the Marker Vaccine Strategy

Single Dose of Consensus Hemagglutinin-Based Virus-Like Particles Vaccine Protects Chickens against Divergent H5 Subtype Influenza Viruses

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