scholarly journals Differential Antigen Requirements for Protection against Systemic and Intranasal Vaccinia Virus Challenges in Mice

2008 ◽  
Vol 82 (14) ◽  
pp. 6829-6837 ◽  
Author(s):  
David R. Kaufman ◽  
Jaap Goudsmit ◽  
Lennart Holterman ◽  
Bonnie A. Ewald ◽  
Matthew Denholtz ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Recombinant Adenovirus ◽  
Protective Efficacy ◽  
Postexposure Prophylaxis ◽  
Virus Challenge ◽  
Protective Antigens ◽  
A Subunit ◽  
Potential Strategy

ABSTRACT The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia virus challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing L1R-specific neutralizing antibodies afforded postexposure prophylaxis after systemic vaccinia virus infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia virus challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia virus challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines.

scholarly journals Cell Culture-Derived Tilapia Lake Virus-Inactivated Vaccine Containing Montanide Adjuvant Provides High Protection against Viral Challenge for Tilapia

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 86
Author(s):  
Weiwei Zeng ◽  
Yingying Wang ◽  
Huzi Hu ◽  
Qing Wang ◽  
Sven M. Bergmann ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Interferon Γ ◽  
Economic Losses ◽  
Mrna Levels ◽  
Infectious Dose ◽  
Booster Immunization ◽  
Virus Challenge ◽  
High Level ◽  
Factor Α

Tilapia lake virus (TiLV) is a newly emerging pathogen responsible for high mortality and economic losses in the global tilapia industry. Currently, no antiviral therapy or vaccines are available for the control of this disease. The goal of the present study was to evaluate the immunological effects and protective efficacy of formaldehyde- and β-propiolactone-inactivated vaccines against TiLV in the presence and absence of the Montanide IMS 1312 VG adjuvant in tilapia. We found that β-propiolactone inactivation of viral particles generated a vaccine with a higher protection efficacy against virus challenge than did formaldehyde. The relative percent survivals of vaccinated fish at doses of 108, 107, and 106 50% tissue culture infectious dose (TCID50)/mL were 42.9%, 28.5%, and 14.3% in the absence of the adjuvant and 85.7%, 64.3%, and 32.1% in its presence, respectively. The vaccine generated specific IgM and neutralizing antibodies against TiLV at 3 weeks following immunization that were significantly increased after a second booster immunization. The steady state mRNA levels of the genes tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon γ (IFN-γ), cluster of differentiation 4 (CD4), major histocompatibility complex (MHC)-Ia, and MHC-II were all increased and indicated successful immune stimulation against TiLV. The vaccine also significantly lowered the viral loads and resulted in significant increases in survival, indicating that the vaccine may also inhibit viral proliferation as well as stimulate a protective antibody response. The β-propiolactone-inactivated TiLV vaccine coupled with the adjuvant Montanide IMS 1312 VG and booster immunizations can provide a high level of protection from virus challenge in tilapia.

scholarly journals Multiparameter Selection of Helicobacter pylori Antigens Identifies Two Novel Antigens with High Protective Efficacy

2002 ◽  
Vol 70 (11) ◽  
pp. 6499-6503 ◽  
Author(s):  
N. Sabarth ◽  
R. Hurwitz ◽  
T. F. Meyer ◽  
D. Bumann
Keyword(s):  
Helicobacter Pylori ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Infection Model ◽  
Protective Antigens ◽  
High Yields ◽  
Selection Of

ABSTRACT A multiparameter selection of Helicobacter pylori antigens for vaccine development identified 15 candidates, 6 of which are known protective antigens. Two novel antigens with low homology to other organisms (HP0231 and HP0410) were overexpressed and purified with high yields. Both confer protective immunity in the mouse Helicobacter infection model.

scholarly journals Single-shot rAAV5-based Vaccine Provides Long-term Protective Immunity against SARS-CoV-2 and Its Variants

2021 ◽  
Author(s):  
Guochao Liao ◽  
Xingxing Fan ◽  
Hungyan Lau ◽  
Zhongqiu Liu ◽  
Chinyu Li ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Challenge Test ◽  
Single Shot ◽  
Strong Immune Response ◽  
Virus Challenge ◽  
Limited Effectiveness ◽  
One Year

SummaryThe COVID-19 pandemic and the SARS-CoV-2 with its variants have posed unprecedented challenges worldwide. Existing vaccines have limited effectiveness against the SARS-CoV-2 variants. Therefore, novel vaccines to match current mutated viral lineages with long-term protective immunity are urgently in demand. In the current study, we for the first time designed a recombinant Adeno-Associated Virus 5 (rAAV5)-based vaccine named as rAAV-COVID-19 vaccine (Covacinplus) by using RBD-plus of spike protein with both the single-stranded and the self-complementary AAV5 delivering vectors (ssAAV5 and scAAAV5), which provides excellent protection from SARS-CoV-2 infection. A single dose vaccination induced the strong immune response against SARS-CoV-2. The induced neutralizing antibodies (NAs) titers were maintained at a high peak level of over 1:1024 even after more than one year of injection and accompanied with functional T-cells responses in mice. Importantly, both ssAAV- and scAAV-based RBD-plus vaccines exhibited high levels of serum NAs against current circulating variants including variants Alpha, Beta, Gamma and Delta. SARS-CoV-2 virus challenge test showed that ssAAV5-RBD-plus vaccine protected both young and old age mice from SARS-CoV-2 infection in the upper and the lower respiratory tracts. Moreover, whole genome sequencing demonstrated that AAV vector DNA sequences were not found in the genome of the vaccinated mice after one year vaccination, demonstrating excellent safety of the vaccine. Taken together, this study suggests that rAAV5-based vaccine is powerful against SARS-CoV-2 and its variants with long-term protective immunity and excellent safety, which has great potential for development into prophylactic vaccination in human to end this global pandemic.

scholarly journals A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine

2007 ◽  
Vol 15 (2) ◽  
pp. 348-358 ◽  
Author(s):  
Anna U. Bielinska ◽  
Alexander A. Chepurnov ◽  
Jeffrey J. Landers ◽  
Katarzyna W. Janczak ◽  
Tatiana S. Chepurnova ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Neutralizing Antibodies ◽  
Clinical Symptoms ◽  
Lethal Dose ◽  
Minimal Risk ◽  
Live Virus ◽  
Virus Challenge ◽  
Lethal Infection ◽  
Nasal Vaccination ◽  
Complete Disruption

ABSTRACT Live-virus vaccines for smallpox are effective but have risks that are no longer acceptable for routine use in populations at minimal risk of infection. We have developed a mucosal, killed-vaccinia virus (VV) vaccine based on antimicrobial nanoemulsion (NE) of soybean oil and detergent. Incubation of VV with 10% NE for at least 60 min causes the complete disruption and inactivation of VV. Simple mixtures of NE and VV (Western Reserve serotype) (VV/NE) applied to the nares of mice resulted in both systemic and mucosal anti-VV immunity, virus-neutralizing antibodies, and Th1-biased cellular responses. Nasal vaccination with VV/NE vaccine produced protection against lethal infection equal to vaccination by scarification, with 100% survival after challenge with 77 times the 50% lethal dose of live VV. However, animals protected with VV/NE immunization did after virus challenge have clinical symptoms more extensive than animals vaccinated by scarification. VV/NE-based vaccines are highly immunogenic and induce protective mucosal and systemic immunity without the need for an inflammatory adjuvant or infection with live virus.

scholarly journals Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels

2015 ◽  
Vol 89 (16) ◽  
pp. 8193-8205 ◽  
Author(s):  
Sandra Fuentes ◽  
Elizabeth M. Coyle ◽  
Hana Golding ◽  
Surender Khurana
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Lung Pathology ◽  
Content Type ◽  
Viral Loads ◽  
Syncytial Virus

ABSTRACTNew efforts are under way to develop a vaccine against respiratory syncytial virus (RSV) that will provide protective immunity without the potential for vaccine-associated disease enhancement such as that observed in infants following vaccination with formalin-inactivated RSV vaccine. In addition to the F fusion protein, the G attachment surface protein is a target for neutralizing antibodies and thus represents an important vaccine candidate. However, glycosylated G protein expressed in mammalian cells has been shown to induce pulmonary eosinophilia upon RSV infection in a mouse model. In the current study, we evaluated in parallel the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain (amino acids 67 to 298) expressed inEscherichia coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model. Vaccination with REG generated neutralizing antibodies against RSV A2 in 7/11 BALB/c mice, while RMG did not elicit neutralizing antibodies. Total serum binding antibodies against the recombinant proteins (both REG and RMG) were measured by surface plasmon resonance (SPR) and were found to be >10-fold higher for REG- than for RMG-vaccinated animals. Reduction of lung viral loads to undetectable levels after homologous (RSV-A2) and heterologous (RSV-B1) viral challenge was observed in 7/8 animals vaccinated with REG but not in RMG-vaccinated animals. Furthermore, enhanced lung pathology and elevated Th2 cytokines/chemokines were observed exclusively in animals vaccinated with RMG (but not in those vaccinated with REG or phosphate-buffered saline [PBS]) after homologous or heterologous RSV challenge. This study suggests that bacterially produced unglycosylated G protein could be developed alone or as a component of a protective vaccine against RSV disease.IMPORTANCENew efforts are under way to develop vaccines against RSV that will provide protective immunity without the potential for disease enhancement. The G attachment protein represents an important candidate for inclusion in an effective RSV vaccine. In the current study, we evaluated the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain produced inE. coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model (strains A2 and B1). The unglycosylated G generated high protective immunity and no lung pathology, even in animals that lacked anti-RSV neutralizing antibodies prior to RSV challenge. Control of viral loads correlated with antibody binding to the G protein. In contrast, the glycosylated G protein provided poor protection and enhanced lung pathology after RSV challenge. Therefore, bacterially produced unglycosylated G protein holds promise as an economical approach to a protective vaccine against RSV.

scholarly journals Immunogenicity and Protective Efficacy of a Polyvalent DNA Vaccine against Human Orthopoxvirus Infections Based on Smallpox Virus Genes

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Rinat A. Maksyutov ◽  
Elena V. Gavrilova ◽  
Galina V. Kochneva ◽  
Sergei N. Shchelkunov
Keyword(s):  
Vaccinia Virus ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Surface Membrane ◽  
Virus Envelope ◽  
Extracellular Virus ◽  
Rous Sarcoma ◽  
Sarcoma Virus

DNA vaccines combining plasmids carrying the variola virus genes M1R, A30L, and F8L of intracellular virion surface membrane proteins as well as A36R and B7R of the extracellular virus envelope proteins under control of Rous sarcoma virus or cytomegalovirus promoters have been constructed. These DNA vaccines induced production of a high titers of vaccinia virus-neutralizing antibodies in mice similar to those elicited by the live vaccinia virus immunization. Mice vaccinated by created DNA vaccine were completely protected against a lethal (10 LD50) challenge with highly pathogenic ectromelia virus. These results suggest that such vaccine should be efficient in immunization of humans against smallpox.

scholarly journals Protective Efficacy of a Single Immunization of a Chimeric Adenovirus Vector-Based Vaccine against Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

2009 ◽  
Vol 83 (18) ◽  
pp. 9584-9590 ◽  
Author(s):  
Dan H. Barouch ◽  
Jinyan Liu ◽  
Diana M. Lynch ◽  
Kara L. O'Brien ◽  
Annalena La Porte ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Rhesus Monkeys ◽  
Recombinant Adenovirus ◽  
Protective Efficacy ◽  
Hypervariable Region ◽  
Adenovirus Vector ◽  
Single Shot ◽  
Virus Challenge ◽  
Immunodeficiency Virus ◽  
Potential Vaccine

ABSTRACT Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologous rAd prime-boost regimen expressing simian immunodeficiency virus (SIV) Gag afforded durable partial immune control of an SIV challenge in rhesus monkeys. However, single-shot immunization may ultimately be preferable for global vaccine delivery. We therefore evaluated the immunogenicity and protective efficacy of a single immunization of chimeric rAd5 hexon hypervariable region 48 (rAd5HVR48) vectors expressing SIV Gag, Pol, Nef, and Env against a homologous SIV challenge in rhesus monkeys. Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system.

scholarly journals Yeast-produced RBD-based recombinant protein vaccines elicit broadly neutralizing antibodies and durable protective immunity against SARS-CoV-2 infection

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jinkai Zang ◽  
Yuanfei Zhu ◽  
Yu Zhou ◽  
Chenjian Gu ◽  
Yufang Yi ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Dose ◽  
Cost Effective ◽  
Prototype Strain ◽  
Broadly Neutralizing Antibodies ◽  
Preclinical Development ◽  
Virus Challenge ◽  
Opening Up

AbstractMassive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

scholarly journals Single dose rVSVΔG-JUNVGP vaccine protects guinea pigs against lethal Junin virus challenge

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Teresa E. Sorvillo ◽  
Robert W. Cross ◽  
Dylan M. Johnson ◽  
Natalie S. Dobias ◽  
Karla A. Fenton ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Neutralizing Antibodies ◽  
Virus Disease ◽  
Protective Efficacy ◽  
The United States ◽  
High Avidity ◽  
Igg Antibody ◽  
Junin Virus ◽  
Virus Challenge ◽  
Junín Virus

AbstractJunin virus (JUNV) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. Currently, there are no JUNV vaccines licensed by the United States Food and Drug Administration (FDA) for at-risk individuals. A vaccine based on recombinant vesicular stomatitis virus (rVSV) has been effectively used to prevent Ebola virus disease in humans. Here, we evaluated the protective efficacy of a rVSV expressing the JUNV glycoprotein (rVSVΔG-JUNVGP) in a guinea pig model of lethal JUNV disease. Two groups of guinea pigs, one prime and one prime-boost, were vaccinated with rVSVΔG-JUNVGP; six control animals remained unvaccinated. Survival for prime and prime-boost vaccinated animals was 100% while the challenge virus was uniformly lethal in all control animals. Animals in both vaccine groups developed robust, high avidity IgG antibody titers post-vaccination as well as detectable neutralizing antibodies while control animals failed to develop detectable antibody responses. This study demonstrates for the first time that rVSV expressing the JUNV GP fully protects guinea pigs from lethal JUNV challenge with a single injection vaccine.

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