DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration

Takamura, Shiki; Niikura, Masahiro; Tc, Li; Takeda, Naokazu; Kusagawa, Shigeru; Takebe, Yutaka; Miyamura, Tatsuo; Yasutomi, Yasuhiro

doi:10.1038/sj.gt.3302193

Cited by 93 publications

(59 citation statements)

References 32 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, HEV VLPs can be a vector for gene delivery to mucosal tissue for the purposes of DNA vaccination and gene therapy (20). The results of the present study provide the basic tool to construct VLPs having novel functions.…”

Section: Discussionmentioning

confidence: 91%

Essential Elements of the Capsid Protein for Self-Assembly into Empty Virus-Like Particles of Hepatitis E Virus

Takeda

Miyamura

et al. 2005

J Virol

166

205

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 91%

Essential Elements of the Capsid Protein for Self-Assembly into Empty Virus-Like Particles of Hepatitis E Virus

Takeda

Miyamura

et al. 2005

J Virol

166

205

View full text Add to dashboard Cite

show abstract

“…The direct correlation between sequence variability and domain functionality may be necessary for the HEV capsid to carry multiple functions and to ensure error-free assembly. It also explains why the transition of HEV-VLP from the Tϭ3 to the Tϭ1 lattice does not disturb its antigenicity and why Tϭ1 VLP can be disassembled and reassembled in vitro to carry foreign antigenic epitopes (30) or DNA plasmids (31).…”

Section: Discussionmentioning

confidence: 99%

Structure of Hepatitis E Virion-sized Particle Reveals an RNA-dependent Viral Assembly Pathway*

Mayazaki

et al. 2010

Journal of Biological Chemistry

149

182

View full text Add to dashboard Cite

Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T‫1؍‬ capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T‫3؍‬ icosahedral lattice and contains RNA fragment in contrast to the RNA-free T‫1؍‬ capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids. Hepatitis E virus (HEV),3 the causative agent of acute hepatitis in humans, is primarily transmitted through contaminated water and generally results in epidemic outbreaks in many developing countries. Sporadic cases have also been reported between outbreaks in HEV-endemic regions as well as in nonendemic areas, and these cases are transmitted through zoonotic route. The overall mortality rates of HEV during outbreaks range from 1 to 15% in general, and the highest mortality occurs in pregnant women, with fatality rates of up to 30% (1).HEV consists of a non-enveloped icosahedral capsid and a single-stranded, positive-strand RNA genome of ϳ7.2 kb that encodes three open reading frames (ORFs) (2). The capsid protein, encoded by the ORF2, is composed of 660 amino acids and responsible for most capsid-related functions, such as virion assembly, host interaction, and immunogenicity. Like other hepatitis viruses, HEV is unable to propagate in currently available cell culture systems, and the research of HEV relies largely on the recombinant HEV capsid proteins (3-6). Virus-like particle (VLP) was obtained when the truncated HEV capsid protein was expressed in insect Tn5 cells with deletion of 52 residues from the C terminus and 111 residues from the N terminus (PORF2) (7). Our previous structural analysis of this HEV-VLP by cryo-electron microscopy (cryo-EM) provided a basic understanding of the quaternary arrangement of PORF2, where the reconstructed VLP displayed a Tϭ1 icosahedral particle composed of 60 copies of PORF2 (8). The essential element of PORF2 protein for Tϭ1 VLP assembly includes amino acids 125-600 (9). Recently, the structural information was further refined by the crystal structures of genotype-3 Tϭ1 VLP (10) and genotype-4 Tϭ1 VLP (11), which revealed the tertiary structure of PORF2 to the level of amino acids. However, the Tϭ1 VLPs used in these experiments were much smaller than that of the native virion, which has a diameter of 320 -340 Å, as determined by immuno-EM (12). There is still a need to investigate the assembly pathway of HEV capsid.HEV virion is hypothesized to be made of 180 copies of the capsid protein (8,11). To test this hypothesis, we screened for HEV genoty...

show abstract

“…Moreover, a high percentage of CTLs was recruited to the Peyer's patches and mesenteric lymph nodes. 73 Similarly, CD4/CD8 T cell and IgA/IgG antibody responses have been observed in the intestines of infant macaques that swallowed a highly attenuated M. tuberculosis expressing SIV Gag followed by a nonreplicating modified vaccinia Ankara (MVA) boost encoding SIV gag/pol/env. 74 On the other hand, contradictory findings were seen in a study conducted by Lin et al in which mice vaccinated with replication-deficient chimpanzee adenovirus via intramuscular or oral routes showed greater induction of both GALT and systemic Gag-specific IFN-c + CD8 responses in the intramuscular animals.…”

Section: Oral Vaccinationmentioning

confidence: 95%

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Poles

Alvarez²,

Hioe³

2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

CD4+ T cells in the mucosa of the gastrointestinal (GI) tract are preferentially targeted and depleted by HIV. As such, the induction of an effective anti-HIV immune response in the mucosa of the GI tract-through vaccination-could protect this vulnerable population of cells. Mucosal vaccination provides a promising means of inducing robust humoral and cellular responses in the GI tract. Here we review data from the literature about the effectiveness of various mucosal vaccination routes-oral (intraintestinal/tonsilar/sublingual), intranasal, and intrarectal-with regard to the induction of immune responses mediated by cytotoxic T cells and antibodies in the GI mucosa, as well as protective efficacy in challenge models. We present data from the literature indicating that mucosal routes have the potential to effectively elicit GI mucosal immunity and protect against challenge. Given their capacity for the induction of anti-HIV immune responses in the GI mucosa, we propose that mucosal routes, including the nonconventional sublingual, tonsilar, and intrarectal routes, be considered for the delivery of the next generation HIV vaccines. However, further studies are necessary to determine the ideal vectors and vaccination regimens for these routes of immunization and to validate their efficacy in controlling HIV infection. HIV Epidemics and Treatment HIV infection has resulted in the death of millions since the early 1980s, and has been responsible for significant morbidity and decline in quality of life for millions more. Each year, an estimated 50,000 people are newly infected with the virus in the United States alone, adding to the 34 million currently living with the virus worldwide.

show abstract

DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration

Cited by 93 publications

References 32 publications

Essential Elements of the Capsid Protein for Self-Assembly into Empty Virus-Like Particles of Hepatitis E Virus

Essential Elements of the Capsid Protein for Self-Assembly into Empty Virus-Like Particles of Hepatitis E Virus

Structure of Hepatitis E Virion-sized Particle Reveals an RNA-dependent Viral Assembly Pathway*

Induction of Intestinal Immunity by Mucosal Vaccines As a Means of Controlling HIV Infection

Contact Info

Product

Resources

About