Multi-antigen avian influenza a (H7N9) virus-like particles: particulate characterizations and immunogenicity evaluation in murine and avian models

Hu, Canbin; Ch, Chien; Liu, Ming‐Tsan; Fang, Zih-Syun; Chang, Sui‐Yuan; Juang, Rong-Huay; Chang, Shih‐Chung; Chen, Hui-Wen

doi:10.1186/s12896-016-0321-6

Cited by 32 publications

(27 citation statements)

References 31 publications

(31 reference statements)

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“…Notably, our synthetic H7-VLP exhibited a haemagglutination activity at a minimum total protein amount of 0.01 μg (Fig. 5 b), which is lower than the minimum total protein amount of H7 VLP exhibiting haemagglutination activity from previous studies of Hu et al [ 9 ] and Pushko et al [ 23 ] of 0.098 and 0.039 μg, respectively. In contrast, in the present study, the free trimeric H7 agglutinated chicken RBCs at a minimum amount of total protein of 5 μg.…”

Section: Discussioncontrasting

confidence: 66%

“…The H7-VLPs vaccine has been shown to elicit highly efficient and protective immune responses against the H7N9 influenza virus because of high molecular weight of H7 formation, which was formed by its self-assembly [ 9 , 21 , 23 ]. According to previous studies on the efficacy of neutralizing antibodies elicited by recombinant HA proteins from avian H5N1 influenza virus, a high-molecular-weight HA oligomer elicited the strongest neutralizing antibody response, followed by the HA trimer, while the monomer showed minimal efficacy [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…These vaccines have been shown to be efficacious against influenza over attenuated or inactivated vaccines [ 23 , 24 ]. Some recent studies have shown that the H7N9 recombinant virus-like particle (VLP) vaccine induced protective immunity against the H7N9 virus in model animals [ 9 , 12 , 23 ]. However, production of these recombinant VLP vaccines is time-consuming.…”

Section: Introductionmentioning

confidence: 99%

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Nanodiamond enhances immune responses in mice against recombinant HA/H7N9 protein

Pham

Nguyen

et al. 2017

J Nanobiotechnol

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BackgroundThe continuing spread of the newly emerged H7N9 virus among poultry in China, as well as the possibility of human-to-human transmission, has attracted numerous efforts to develop an effective vaccine against H7N9. The use of nanoparticles in vaccinology is inspired by the fact that most pathogens have a dimension within the nano-size range and therefore can be processed efficiently by the immune system, which leads to a potent immune response. Herein, we report a facile approach to increase antigen size to achieve not only fast but also effective responses against the recombinant HA/H7N9 protein via a simple conjugation of the protein onto the surface of nanodiamond particles.ResultsIn this study, trimeric Haemagglutinin (H7) that is transiently expressed in N. benthamiana was purified using affinity chromatography, and its trimeric state was revealed successfully by the cross-linking reaction. The trimeric H7 solution was subsequently mixed with a nanodiamond suspension in different ratios. The successful conjugation of the trimeric H7 onto the surface of nanodiamond particles was demonstrated by the changes in size and Zeta-potential of the particles before and after protein coating, Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and Western-blot analysis. Next, biofunction of the protein-nanodiamond conjugates was screened using a haemagglutination assay. A mixture containing 5 µg of trimeric H7 and 60 µg of nanodiamond corresponds to a ratio of 1:12 (w/w) of agglutinated chicken red blood cells at HA titer of 1024, which is 512-fold higher than the HA titer of free trimeric H7. After the 2nd and 3rd immunization in mice, ELISA and Western blot analyses demonstrated that the physical mixture of trimeric H7 protein and nanodiamond (1:12, w/w) elicited statistically significant stronger H7-specific-IgG response demonstrated by higher amounts of H7N9-specific IgG (over 15.4-fold with P < 0.05 after the second immunization).ConclusionsThese results indicated a potential effect inherent to nanodiamond towards modulating immune systems, which should be further evaluated and broadly applied in nanovaccine development.

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Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nanodiamond enhances immune responses in mice against recombinant HA/H7N9 protein

Pham

Nguyen

et al. 2017

J Nanobiotechnol

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“…Recent studies have demonstrated that live attenuated A(H7N9) vaccine, inactivated cell-cultured whole-virus A(H7N9) vaccine, and virus-like particles bearing HA, NA, and M1 of A(H7N9) virus all induce significant N9 antibody titers in animal models (45)(46)(47). The contribution of NA immunity in ameliorating human A(H7N9) infections deserves further investigation in order to improve A(H7N9) vaccines.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Wan

Gao

et al. 2018

J Virol

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The fifth wave of A(H7N9) virus infection in China from 2016 to 2017 caused great concern due to the large number of individuals infected, the isolation of drug-resistant viruses, and the emergence of highly pathogenic strains. Antibodies against neuraminidase (NA) provide added benefit to hemagglutinin-specific immunity and may be important contributors to the effectiveness of A(H7N9) vaccines. We generated a panel of mouse monoclonal antibodies (MAbs) to identify antigenic domains on NA of the novel A(H7N9) virus and compared their functional properties. The loop formed in the region of residue 250 (250 loop) and the domain formed by the loops containing residues 370, 400, and 430 were identified as major antigenic regions. MAbs 1E8, 2F6, 10F4, and 11B2, which recognize these two antigenic domains, were characterized in depth. These four MAbs differ in their abilities to inhibit cleavage of small and large substrates (methyl-umbelliferylacetyl neuraminic acid [MU-NANA] and fetuin, respectively) in NA inhibition assays. 1E8 and 11B2 did not inhibit NA cleavage of either MU-NANA or fetuin, and 2F6 inhibited cleavage of fetuin alone, whereas 10F4 inhibited cleavage of both substrates. All four MAbs reduced the in vitro spread of viruses carrying either the wild-type N9 or N9 with antiviral-resistant mutations but to different degrees. These MAbs have different in vivo levels of effectiveness: 10F4 was the most effective in protecting mice against challenge with A(H7N9) virus, 2F6 was less effective, and 11B2 failed to protect BALB/c mice at the doses tested. Our study confirms that NA-specific antibodies can protect against A(H7N9) infection and suggests that in vitro properties can be used to rank antibodies with therapeutic potential. IMPORTANCEThe novel A(H7N9) viruses that emerged in China in 2013 continue to infect humans, with a high fatality rate. The most recent outbreak resulted in a larger number of human cases than previous epidemic waves. Due to the absence of a licensed vaccine and the emergence of drug-resistant viruses, there is a need to develop alternative approaches to prevent or treat A(H7N9) infection. We have made a panel of mouse monoclonal antibodies (MAbs) specific for neuraminidase (NA) of A(H7N9) viruses; some of these MAbs are effective in inhibiting viruses that are resistant to antivirals used to treat A(H7N9) patients. Binding avidity, inhibition of NA activity, and plaque formation correlated with the effectiveness of these MAbs to protect mice against lethal A(H7N9) virus challenge. This study identifies in vitro measures that can be used to predict the in vivo efficacy of NA-specific antibodies, providing a way to select MAbs for further therapeutic development.

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“…Although synthetically prepared nanoparticles have yet to show the level of ordered antigen arrangement found on viruses and virus-like particles derived from cell culture systems [181,182], ongoing studies continue to demonstrate emerging techniques to couple antigens of interest to nanocarriers. In the last section of the review, we review commonly used methods for coupling antigens with nanoparticles.…”

Section: Repetitive Antigen Display For Immune Activationmentioning

confidence: 99%

Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

et al. 2017

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Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases.

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Multi-antigen avian influenza a (H7N9) virus-like particles: particulate characterizations and immunogenicity evaluation in murine and avian models

Cited by 32 publications

References 31 publications

Nanodiamond enhances immune responses in mice against recombinant HA/H7N9 protein

Nanodiamond enhances immune responses in mice against recombinant HA/H7N9 protein

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

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