scholarly journals Novel virus-like particle vaccine encoding the circumsporozoite protein of Plasmodium falciparum is immunogenic and induces functional antibody responses

2020 ◽  
Author(s):  
Liriye Kurtovic ◽  
David Wetzel ◽  
Linda Reiling ◽  
Damien R. Drew ◽  
Catherine Palmer ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Protective Efficacy ◽  
Scaffold Protein ◽  
Circumsporozoite Protein ◽  
Small Surface ◽  
Duck Hepatitis ◽  
Virus Like Particle ◽  
B Virus ◽  
Multiple Regions

RTS,S is the leading malaria vaccine in development, but has demonstrated only moderate protective efficacy in clinical trials. RTS,S is a virus-like particle (VLP) that uses the human hepatitis B virus as scaffold to display the malaria sporozoite antigen, circumsporozoite protein (CSP). Particle formation requires fourfold excess scaffold antigen, and as a result, CSP represents only a small portion of the final vaccine construct. Alternative VLP or nanoparticle platforms that reduce the amount of scaffold antigen and increase the amount of the target CSP antigen present in particles may enhance vaccine immunogenicity and efficacy. Here, we describe the production and characterization of a novel VLP that uses the small surface antigen (dS) of duck hepatitis B virus to display CSP. The CSP-dS fusion protein successfully formed VLPs without the need for excess scaffold antigen, and thus CSP represented a larger portion of the vaccine construct. Importantly, this is the first report of a dS-based vaccine that formed particles without excess scaffold protein. CSP-dS formed large particles approximately 31-74 nm in size and were confirmed to display CSP on the surface. The CSP-dS VLP was highly immunogenic in mice and induced antibodies to multiple regions of CSP, even when administered at a lower vaccine dosage. Vaccine-induced antibodies demonstrated functional activity, including the ability to interact with complement and Fcγ-receptors, both previously identified as important in malaria immunity. Our novel platform to produce VLPs without excess scaffold protein has wide implications for the future development of innovative vaccines for malaria and other infectious diseases.

scholarly journals Novel Virus-Like Particle Vaccine Encoding the Circumsporozoite Protein of Plasmodium falciparum Is Immunogenic and Induces Functional Antibody Responses in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Liriye Kurtovic ◽  
David Wetzel ◽  
Linda Reiling ◽  
Damien R. Drew ◽  
Catherine Palmer ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Protective Efficacy ◽  
Circumsporozoite Protein ◽  
Small Surface ◽  
Functional Activities ◽  
Duck Hepatitis ◽  
Virus Like Particle ◽  
B Virus ◽  
Multiple Regions

RTS,S is the leading malaria vaccine in development, but has demonstrated only moderate protective efficacy in clinical trials. RTS,S is a virus-like particle (VLP) that uses the human hepatitis B virus as scaffold to display the malaria sporozoite antigen, circumsporozoite protein (CSP). Particle formation requires four-fold excess scaffold antigen, and as a result, CSP represents only a small portion of the final vaccine construct. Alternative VLP or nanoparticle platforms that reduce the amount of scaffold antigen and increase the amount of the target CSP antigen present in particles may enhance vaccine immunogenicity and efficacy. Here, we describe the production and characterization of a novel VLP that uses the small surface antigen (dS) of duck hepatitis B virus to display CSP. The CSP-dS fusion protein successfully formed VLPs without the need for excess scaffold antigen, and thus CSP represented a larger portion of the vaccine construct. CSP-dS formed large particles approximately 31-74 nm in size and were confirmed to display CSP on the surface. CSP-dS VLPs were highly immunogenic in mice and induced antibodies to multiple regions of CSP, even when administered at a lower vaccine dosage. Vaccine-induced antibodies demonstrated relevant functional activities, including Fc-dependent interactions with complement and Fcγ-receptors, previously identified as important in malaria immunity. Further, vaccine-induced antibodies had similar properties (epitope-specificity and avidity) to monoclonal antibodies that are protective in mouse models. Our novel platform to produce VLPs without excess scaffold protein has wide implications for the future development of vaccines for malaria and other infectious diseases.

scholarly journals Protective Efficacy of DNA Vaccines against Duck Hepatitis B Virus Infection

1998 ◽  
Vol 72 (1) ◽  
pp. 84-94 ◽  
Author(s):  
M. Triyatni ◽  
A. R. Jilbert ◽  
M. Qiao ◽  
D. S. Miller ◽  
C. J. Burrell
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Virus Replication ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Virus Infectivity ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus ◽  
S Proteins

ABSTRACT The efficacy of DNA vaccines encoding the duck hepatitis B virus (DHBV) pre-S/S and S proteins were tested in Pekin ducks. Plasmid pcDNA I/Amp DNA containing the DHBV pre-S/S or S genes was injected intramuscularly three times, at 3-week intervals. All pre-S/S and S-vaccinated ducks developed total anti-DHBs and specific anti-S antibodies with similar titers reaching 1/10,000 to 1/50,000 and 1/2,500 to 1/4,000, respectively, after the third vaccination. However, following virus challenge, significant differences in the rate of virus removal from the bloodstream and the presence of virus replication in the liver were found between the groups. In three of four S-vaccinated ducks, 90% of the inoculum was removed between <5 and 15 min postchallenge (p.c.) and no virus replication was detected in the liver at 4 days p.c. In contrast, in all four pre-S/S-vaccinated ducks, 90% of the inoculum was removed between 60 and 90 min p.c. and DHBsAg was detected in 10 to 40% of hepatocytes. Anti-S serum abolished virus infectivity when preincubated with DHBV before inoculation into 1-day-old ducklings and primary duck hepatocyte cultures, while anti-pre-S/S serum showed very limited capacity to neutralize virus infectivity in these two systems. Thus, although both DNA vaccines induced high titers of anti-DHBs antibodies, anti-S antibodies induced by the S-DNA construct were highly effective in neutralizing virus infectivity while similar levels of anti-S induced by the pre-S/S-DNA construct conferred only very limited protection. This phenomenon requires further clarification, particularly in light of the development of newer HBV vaccines containing pre-S proteins and a possible discrepancy between anti-HBs titers and protective efficacy.

Integrated structures of duck hepatitis B virus DNA in hepatocellular carcinoma.

1988 ◽  
Vol 62 (3) ◽  
pp. 861-865 ◽  
Author(s):  
F Imazeki ◽  
K Yaginuma ◽  
M Omata ◽  
K Okuda ◽  
M Kobayashi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Duck Hepatitis B Virus ◽  
Hepatitis B Virus Dna ◽  
Duck Hepatitis ◽  
B Virus ◽  
Integrated Structures

scholarly journals New Hepatitis B Virus of Cranes That Has an Unexpected Broad Host Range

2003 ◽  
Vol 77 (3) ◽  
pp. 1964-1976 ◽  
Author(s):  
Alexej Prassolov ◽  
Heinz Hohenberg ◽  
Tatyana Kalinina ◽  
Carola Schneider ◽  
Lucyna Cova ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Host Range ◽  
Sequence Divergence ◽  
Divergent Evolution ◽  
Broad Host Range ◽  
Virus Propagation ◽  
Direct Dna Sequencing ◽  
Duck Hepatitis ◽  
B Virus

ABSTRACT All hepadnaviruses known so far have a very limited host range, restricted to their natural hosts and a few closely related species. This is thought to be due mainly to sequence divergence in the large envelope protein and species-specific differences in host components essential for virus propagation. Here we report an infection of cranes with a novel hepadnavirus, designated CHBV, that has an unexpectedly broad host range and is only distantly evolutionarily related to avihepadnaviruses of related hosts. Direct DNA sequencing of amplified CHBV DNA as well a sequencing of cloned viral genomes revealed that CHBV is most closely related to, although distinct from, Ross' goose hepatitis B virus (RGHBV) and slightly less closely related to duck hepatitis B virus (DHBV). Phylogenetically, cranes are very distant from geese and ducks and are most closely related to herons and storks. Naturally occurring hepadnaviruses in the last two species are highly divergent in sequence from RGHBV and DHBV and do not infect ducks or do so only marginally. In contrast, CHBV from crane sera and recombinant CHBV produced from LMH cells infected primary duck hepatocytes almost as efficiently as DHBV did. This is the first report of a rather broad host range of an avihepadnavirus. Our data imply either usage of similar or identical entry pathways and receptors by DHBV and CHBV, unusual host and virus adaptation mechanisms, or divergent evolution of the host genomes and cellular components required for virus propagation.

Fine Mapping of Neutralization Epitopes on Duck Hepatitis B Virus (DHBV) pre-S Protein Using Monoclonal Antibodies and Overlapping Peptides

Virology ◽  
1993 ◽  
Vol 192 (1) ◽  
pp. 217-223 ◽  
Author(s):  
Sylvie Chassot ◽  
Véronique Lambert ◽  
Alan Kay ◽  
Catherine Godinot ◽  
Bernard Roux ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Fine Mapping ◽  
Duck Hepatitis B Virus ◽  
S Protein ◽  
Duck Hepatitis ◽  
B Virus

Duck hepatitis B virus: Cloning and subcloning of the viral genome

1989 ◽  
Vol 270 (3) ◽  
pp. 424-433
Author(s):  
Konrad Oexle ◽  
Hubert E. Blum ◽  
Eike Walter ◽  
Wolf-Bernhard Offensperger ◽  
Silke Offensperger ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Viral Genome ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

scholarly journals Duck hepatitis B virus: a model to assess efficacy of disinfectants against hepadnavirus infectivity

1991 ◽  
Vol 106 (3) ◽  
pp. 435-443 ◽  
Author(s):  
S. M. Murray ◽  
J. S. Freiman ◽  
K. Vickery ◽  
D. Lim ◽  
Y. E. Cossart ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Room Temperature ◽  
Virus Titre ◽  
Experimental Protocol ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus ◽  
Undiluted Serum ◽  
Sterile Filter

SUMMARYThe efficacy of three proprietary glutaraldehyde disinfectants and their component bases was assessed using the duck hepatitis B virus (DHBV) model. Inactivation of infectivity of undiluted serum containing 106·8ID50/ml DHBV was assessed after a mixture with an equal volume of disinfectant had stood at room temperature for 10 min. A dried spill of infectious serum was simulated using sterile filter paper disks, saturated with serum containing DHBV, dried and then exposed to test disinfectant for 10 min. Residual infectivity, and hence the reduction in virus titre, was determined by inoculation of dilutions of the treated samples into 1-day-old ducklings. A greater than 3 log10reduction in virus titre could be demonstrated for the disinfectants as well as for some of their component bases. Disinfectant activity varied according to the method of viral presentation but a reduction of exposure time from 10 to 2·5 min did not diminish activity. The experimental protocol permits a comparative and quantitative assessment of the efficacy of both established and new disinfectants.

scholarly journals Rise in gamma interferon expression during resolution of duck hepatitis B virus infection

2006 ◽  
Vol 87 (11) ◽  
pp. 3225-3232 ◽  
Author(s):  
Ramamurthy Narayan ◽  
Thierry Buronfosse ◽  
Ursula Schultz ◽  
Philippe Chevallier-Gueyron ◽  
Sylviane Guerret ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Mononuclear Cells ◽  
Reference Model ◽  
Gamma Interferon ◽  
Strong Increase ◽  
Moderate Increase ◽  
Histological Changes ◽  
Duck Hepatitis ◽  
B Virus

Gamma interferon (IFN-γ) expression plays a crucial role in the control of mammalian hepatitis B virus (HBV) infection. However, the role of duck INF-γ (DuIFN-γ) in the outcome of duck HBV (DHBV) infection, a reference model for hepadnavirus replication studies, has not yet been investigated. This work explored the dynamics of DuIFN-γ expression in liver and peripheral blood mononuclear cells (PBMCs) during resolution of DHBV infection in adolescent ducks in relation to serum and liver markers of virus replication, histological changes and humoral response induction. DHBV infection of 3-week-old ducks resulted in transient expression of intrahepatic preS protein (days 3–14) and mild histological changes. Low-level viraemia was detected only during the first 10 days of infection and was accompanied by early anti-preS antibody response induction. Importantly, a strong increase in intrahepatic DuIFN-γ RNA was detected by real-time RT-PCR at days 6–14, which coincided with a sharp decrease in both viral DNA and preS protein in the liver. Interestingly, liver DuIFN-γ expression remained augmented to the end of the follow-up period (day 66) and correlated with portal lymphocyte infiltration and persistence of trace quantities of intrahepatic DHBV DNA in animals that had apparently completely resolved the infection. Moreover, in infected ducks, a moderate increase was detected in the levels of DuIFN-γ in PBMCs (days 12–14), which coincided with the peak in liver DuIFN-γ RNA levels. These data reveal that increased DuIFN-γ expression in liver and PBMCs is concomitant with viral clearance, characterizing the resolution of infection, and provide new insights into the host–virus interactions that control DHBV infection.

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