Vaccination of BALB/c Mice with Escherichia coli-Expressed Vaccinia Virus Proteins A27L, B5R, and D8L Protects Mice from Lethal Vaccinia Virus Challenge

ABSTRACT The potential threat of smallpox use in a bioterrorist attack has heightened the need to develop an effective smallpox vaccine for immunization of the general public. Vaccination with the current smallpox vaccine, Dryvax, produces protective immunity but may result in adverse reactions for some vaccinees. A subunit vaccine composed of protective vaccinia virus proteins should avoid the complications arising from live-virus vaccination and thus provide a safer alternative smallpox vaccine. In this study, we assessed the protective efficacy and immunogenicity of a multisubunit vaccine composed of the A27L and D8L proteins from the intracellular mature virus (IMV) form and the B5R protein from the extracellular enveloped virus (EEV) form of vaccinia virus. BALB/c mice were immunized with Escherichia coli-produced A27L, D8L, and B5R proteins in an adjuvant consisting of monophosphoryl lipid A and trehalose dicorynomycolate or in TiterMax Gold adjuvant. Following immunization, mice were either sacrificed for analysis of immune responses or lethally challenged by intranasal inoculation with vaccinia virus strain Western Reserve. We observed that three immunizations either with A27L, D8L, and B5R or with the A27L and B5R proteins alone induced potent neutralizing antibody responses and provided complete protection against lethal vaccinia virus challenge. Several linear B-cell epitopes within the three proteins were recognized by sera from the immunized mice. In addition, protein-specific cellular responses were detected in spleens of immunized mice by a gamma interferon enzyme-linked immunospot assay using peptides derived from each protein. Our data suggest that a subunit vaccine incorporating bacterially expressed IMV- and EEV-specific proteins can be effective in stimulating anti-vaccinia virus immune responses and providing protection against lethal virus challenge.

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Protection against Lethal Leptospirosis after Vaccination with LipL32 Coupled or Coadministered with the B Subunit of Escherichia coli Heat-Labile Enterotoxin

Clinical and Vaccine Immunology ◽

10.1128/cvi.05720-11 ◽

2012 ◽

Vol 19 (5) ◽

pp. 740-745 ◽

Cited By ~ 35

Author(s):

André A. Grassmann ◽

Samuel R. Félix ◽

Carolina Ximendes dos Santos ◽

Marta G. Amaral ◽

Amilton C. P. Seixas Neto ◽

...

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

Subunit Vaccine ◽

Lethal Dose ◽

Control Group ◽

Hamster Model ◽

Content Type ◽

B Subunit ◽

Heat Labile ◽

A Subunit

ABSTRACTLeptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species ofLeptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of theEscherichia coliheat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) ofLeptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P< 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.

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Penton base induces better protective immune responses than fiber and hexon as a subunit vaccine candidate against adenoviruses

Vaccine ◽

10.1016/j.vaccine.2018.05.118 ◽

2018 ◽

Vol 36 (29) ◽

pp. 4287-4297 ◽

Cited By ~ 2

Author(s):

Kai Hu ◽

Ming Fu ◽

Xinmeng Guan ◽

Di Zhang ◽

Xu Deng ◽

...

Keyword(s):

Immune Responses ◽

Subunit Vaccine ◽

Vaccine Candidate ◽

Penton Base ◽

A Subunit

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Coadministration of Cidofovir and Smallpox Vaccine Reduced Vaccination Side Effects but Interfered with Vaccine-Elicited Immune Responses and Immunity to Monkeypox

Journal of Virology ◽

10.1128/jvi.00984-08 ◽

2008 ◽

Vol 83 (2) ◽

pp. 1115-1125 ◽

Cited By ~ 11

Author(s):

Huiyong Wei ◽

Dan Huang ◽

Jeff Fortman ◽

Richard Wang ◽

Linyun Shao ◽

...

Keyword(s):

Single Dose ◽

Side Effects ◽

Immune Responses ◽

Antiviral Agent ◽

Smallpox Vaccine ◽

Effector Cells ◽

Virus Challenge ◽

T Effector Cells ◽

Viral Loads ◽

Induced Immunity

ABSTRACT While the smallpox vaccine, Dryvax or Dryvax-derived ACAM2000, holds potential for public immunization against the spread of smallpox by bioterror, there is serious concern about Dryvax-mediated side effects. Here, we report that a single-dose vaccination regimen comprised of Dryvax and an antiviral agent, cidofovir, could reduce vaccinia viral loads after vaccination and significantly control Dryvax vaccination side effects. However, coadministration of cidofovir and Dryvax also reduced vaccine-elicited immune responses of antibody and T effector cells despite the fact that the reduced priming could be boosted as a recall response after monkeypox virus challenge. Evaluations of four different aspects of vaccine efficacy showed that coadministration of cidofovir and Dryvax compromised the Dryvax-induced immunity against monkeypox, although the covaccinated monkeys exhibited measurable protection against monkeypox compared to that of naïve controls. Thus, the single-dose coadministration of cidofovir and Dryvax effectively controlled vaccination side effects but significantly compromised vaccine-elicited immune responses and vaccine-induced immunity to monkeypox.

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Passive Transfer of Serum Antibodies Induced by BBG2Na, a Subunit Vaccine, in the Elderly Protects SCID Mouse Lungs Against Respiratory Syncytial Virus Challenge

Virology ◽

10.1006/viro.2002.1563 ◽

2002 ◽

Vol 303 (1) ◽

pp. 130-137 ◽

Cited By ~ 14

Author(s):

Hélène Plotnicky-Gilquin ◽

Dominique Cyblat-Chanal ◽

Liliane Goetsch ◽

Christine Lacheny ◽

Christine Libon ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Scid Mouse ◽

Subunit Vaccine ◽

The Elderly ◽

Passive Transfer ◽

Serum Antibodies ◽

Virus Challenge ◽

A Subunit ◽

Syncytial Virus ◽

Mouse Lungs

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A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00440-07 ◽

2007 ◽

Vol 15 (2) ◽

pp. 348-358 ◽

Cited By ~ 35

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.

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Coagulases as Determinants of Protective Immune Responses against Staphylococcus aureus

Infection and Immunity ◽

10.1128/iai.00562-12 ◽

2012 ◽

Vol 80 (10) ◽

pp. 3389-3398 ◽

Cited By ~ 44

Author(s):

Molly McAdow ◽

Andrea C. DeDent ◽

Carla Emolo ◽

Alice G. Cheng ◽

Barry N. Kreiswirth ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Immune Responses ◽

Von Willebrand Factor ◽

Subunit Vaccine ◽

Gene Sequences ◽

Content Type ◽

A Subunit ◽

Von Willebrand ◽

Willebrand Factor

ABSTRACTDuring infection,Staphylococcus aureussecretes two coagulases (Coa and von Willebrand factor binding protein [vWbp]), which, following an association with host prothrombin and fibrinogen, form fibrin clots and enable the establishment of staphylococcal disease. Within the genomes of differentS. aureusisolates, coagulase gene sequences are variable, and this has been exploited for a classification of types. We show here that antibodies directed against the variable prothrombin binding portion of coagulases confer type-specific immunity through the neutralization ofS. aureusclotting activity and protection from staphylococcal disease in mice. By combining variable portions of coagulases from North American isolates into hybrid Coa and vWbp proteins, a subunit vaccine that provided protection against challenge with different coagulase-typeS. aureusstrains in mice was derived.

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Biochemical and Immunological Evaluation of Recombinant CS6-Derived Subunit EnterotoxigenicEscherichia coliVaccine Candidates

Infection and Immunity ◽

10.1128/iai.00788-18 ◽

2019 ◽

Vol 87 (3) ◽

Cited By ~ 4

Author(s):

Steven T. Poole ◽

Milton Maciel ◽

Premkumar Dinadayala ◽

Kathleen E. Dori ◽

Annette L. McVeigh ◽

...

Keyword(s):

Immune Responses ◽

Recombinant Proteins ◽

Neutralizing Antibodies ◽

Subunit Vaccine ◽

Vaccine Strategy ◽

Content Type ◽

A Subunit ◽

Folded Proteins ◽

Immunological Evaluation

ABSTRACTCS6, a prevalent surface antigen expressed in nearly 20% of clinical enterotoxigenicEscherichia coli(ETEC) isolates, is comprised of two major subunit proteins, CssA and CssB. Using donor strand complementation, we constructed a panel of recombinant proteins of 1 to 3 subunits that contained combinations of CssA and/or CssB subunits and a donor strand, a C-terminal extension of 16 amino acids that was derived from the N terminus of either CssA or CssB. While the entire panel of recombinant proteins could be obtained as soluble, folded proteins, it was observed that the proteins possessing a heterologous donor strand, derived from the CS6 subunit different from the C-terminal subunit, had the highest degree of physical and thermal stability. Immunological characterization of the proteins, using a murine model, demonstrated that robust anti-CS6 immune responses were generated from fusions containing both CssA and CssB. Proteins containing only CssA were weakly immunogenic. Heterodimers, i.e., CssBA and CssAB, were sufficient to recapitulate the anti-CS6 immune response elicited by immunization with CS6, including the generation of functional neutralizing antibodies, as no further enhancement of the response was obtained with the addition of a third CS6 subunit. Our findings here demonstrate the feasibility of including a recombinant CS6 subunit protein in a subunit vaccine strategy against ETEC.

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

Journal of Virology ◽

10.1128/jvi.00353-08 ◽

2008 ◽

Vol 82 (14) ◽

pp. 6829-6837 ◽

Cited By ~ 24

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.

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