Chimeric Bivalent Virus-Like Particle Vaccine for H5N1 HPAI and ND Confers Protection against a Lethal Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals (DIVA)

Noh, Jin-Yong; Park, Jae-Keun; Lee, Donghun; Yuk, Seong‐Su; Kwon, Jung‐Hoon; Lee, Sang‐Won; Park, Seung‐Yong; Choi, In‐Soo; Song, Chang‐Seon

doi:10.1371/journal.pone.0162946

Cited by 18 publications

(9 citation statements)

References 33 publications

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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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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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“…F is thought to be the predominant antigen in NDV vaccine studies. Antibodies elicited by the F protein can protect chickens from lethal NDV challenge [2,13,14,15,16].…”

Section: Introductionmentioning

confidence: 99%

Construction and Immunogenicity of Novel Chimeric Virus-Like Particles Bearing Antigens of Infectious Bronchitis Virus and Newcastle Disease Virus

Wu¹,

Zhai²,

Lai³

et al. 2019

Viruses

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Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV) are two poultry pathogens seriously affecting the poultry industry. Here, IBV S1 and the ectodomain of NDV F proteins were separately linked with the trans-membrane and carboxy-terminal domain of IBV S protein (STMCT), composing rS and rF; thus, a novel chimeric infectious bronchitis-Newcastle disease (IB-ND) virus-like particles (VLPs) vaccine containing the rS, rF, and IBV M protein was constructed. Under the transmission electron microscope (TEM), VLPs possessing similar morphology to natural IBV were observed. To evaluate the immunogenicity of chimeric IB-ND VLPs, specific pathogen-free (SPF) chickens were immunized with three increasing doses (50, 75, and 100 μg protein of VLPs). Results of ELISAs detecting IBV and NDV specific antibodies and IL-4 and IFN-γ T cell cytokines indicated that vaccination with chimeric IB-ND VLPs could efficiently induce humoral and cellular immune responses. In the challenge study, chimeric IB-ND VLPs (100 μg protein) provided 100% protection against IBV or NDV virulent challenge from death, and viral RNA levels in tissues and swabs were greatly reduced. Collectively, chimeric IB-ND VLPs are highly immunogenic and could provide complete protection from an IBV or NDV virulent challenge. Chimeric IB-ND VLPs are an appealing vaccine candidate and a promising vaccine platform bearing multivalent antigens.

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“…phosphorylation, glycosylation), and their potential for contamination with biologically compatible zoonotic viruses. Protein expression for the production of VLP is highly amenable to modification, such as substituting strain-specific amino acid sequences [43], or inserting foreign peptide sequences or proteins [44,45]. Manipulation of this process can facilitate the engineering of recombinant chimeric VLP containing xenogeneic antigens, inducing an immune response against targets other than the parent virus [46].…”

Section: Modification Of Vlpmentioning

confidence: 99%

Virus-like particle vaccines: immunology and formulation for clinical translation

Donaldson

Lateef

Walker

et al. 2018

Expert Review of Vaccines

129

105

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Virus-like particle (VLP) vaccines face significant challenges in their translation from laboratory models, to routine clinical administration. While some VLP vaccines thrive and are readily adopted into the vaccination schedule, others are restrained by regulatory obstacles, proprietary limitations, or finding their niche amongst the crowded vaccine market. Often the necessity to supplant an existing vaccination regimen possesses an immediate obstacle for the development of a VLP vaccine, despite any preclinical advantages identified over the competition. Novelty, adaptability and formulation compatibility may prove invaluable in helping place VLP vaccines at the forefront of vaccination technology. Areas covered: The purpose of this review is to outline the diversity of VLP vaccines, VLP-specific immune responses, and to explore how modern formulation and delivery techniques can enhance the clinical relevance and overall success of VLP vaccines. Expert commentary: The role of formation science, with an emphasis on the diversity of immune responses induced by VLP, is underrepresented amongst clinical trials for VLP vaccines. Harnessing such diversity, particularly through the use of combinations of select excipients and adjuvants, will be paramount in the development of VLP vaccines.

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Chimeric Bivalent Virus-Like Particle Vaccine for H5N1 HPAI and ND Confers Protection against a Lethal Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals (DIVA)

Cited by 18 publications

References 33 publications

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

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

Construction and Immunogenicity of Novel Chimeric Virus-Like Particles Bearing Antigens of Infectious Bronchitis Virus and Newcastle Disease Virus

Virus-like particle vaccines: immunology and formulation for clinical translation

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