Evaluation of Venezuelan Equine Encephalitis (VEE) replicon-based Outer surface protein A (OspA) vaccines in a tick challenge mouse model of Lyme disease

Gipson, Clay L.; Davis, Nancy; Johnston, Robert E.; Silva, Aravinda M. de

doi:10.1016/s0264-410x(03)00307-4

Cited by 14 publications

(14 citation statements)

References 29 publications

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“…It has been reported that antigen delivery using a VRP vehicle can result in enhanced antigen-specific serum IgA expression (76), but we were unable to detect this isotype after HA-DNA and HA-VRP vaccination. The low levels of IgG2b and IgG3 observed after gene gun and VRP vaccination are similar to what has been reported previously (16,23). Taken together, the analyses of different serum antibody isotypes after vaccination with this regimen strengthen the argument that vaccine-induced IgG1 and IgG2a antibodies contribute to the protective responses observed.…”

Section: Discussionsupporting

confidence: 89%

“…We delivered influenza HA expressed in plasmid DNA via the gene gun, a route of vaccination that is known to induce a predominantly IgG1 response in BALB/c mice (16,41,76). We then vaccinated mice with replication-deficient viral replicon particles (VRP) from Venezuelan equine encephalitis (VEE) virus, which express the influenza HA in a manner known to enhance IgG2a antibody levels in mice (23,75,76). Our results support a role for IgG1 antibodies in the neutralization of viral particles both in vitro and in vivo.…”

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confidence: 99%

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Distinct Contributions of Vaccine-Induced Immunoglobulin G1 (IgG1) and IgG2a Antibodies to Protective Immunity against Influenza

Huber

McKeon

Brackin

et al. 2006

Clin Vaccine Immunol

271

257

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Vaccination represents the most effective form of protection against influenza infection. While neutralizing antibodies are typically measured as a correlate of vaccine-induced protective immunity against influenza, nonneutralizing antibodies may contribute to protection or amelioration of disease. The goal of this study was to dissect the individual contributions of the immunoglobulin G1 (IgG1) and IgG2a antibody isotypes to vaccine-induced immunity against influenza virus. To accomplish this, we utilized an influenza vaccine regimen that selectively enhanced IgG1 or IgG2a antibodies by using either DNA or viral replicon particle (VRP) vectors expressing influenza virus hemagglutinin (HA) (HA-DNA or HA-VRP, respectively). After HA-DNA vaccination, neutralizing antibodies were detected by both in vitro (microneutralization) and in vivo (lung viral titer) methods and were associated with increased IgG1 expression by enzyme-linked immunosorbent assay (ELISA). Vaccination with HA-VRP did not strongly stimulate either neutralizing or IgG1 antibodies but did induce IgG2a antibodies. Expression of IgG2a antibodies in this context correlated with clearance of virus and increased protection against lethal influenza challenge. Increased induction of both antibody isotypes as measured by ELISA was a better correlate for vaccine efficacy than neutralization alone. This study details separate but important roles for both IgG1 and IgG2a expression in vaccination against influenza and argues for the development of vaccine regimens that stimulate and measure expression of both antibody isotypes.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Distinct Contributions of Vaccine-Induced Immunoglobulin G1 (IgG1) and IgG2a Antibodies to Protective Immunity against Influenza

Huber

McKeon

Brackin

et al. 2006

Clin Vaccine Immunol

271

257

View full text Add to dashboard Cite

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“…This unexpected result might be explained by the antigenic characteristics inherent in TbpB or by the relatively greater immunogenicity of the nonsecreted fraction of tPA-TbpB. However, this bias is consistent with the observations of Gipson et al for the OspA protein expressed under similar circumstances (14).…”

Section: Discussionsupporting

confidence: 89%

“…More recently, a number of bacterial proteins have been expressed in this system, including botulinum neurotoxin (23), Borrelia burgdorferi OspA (14), staphylococcal enterotoxin (21), and the protective antigen from Bacillus anthracis (22). In this study, we tested VEE VRPs as a potential platform for a gonococcal vaccine.…”

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confidence: 99%

Vaccination of Mice with Gonococcal TbpB Expressed In Vivo from Venezuelan Equine Encephalitis Viral Replicon Particles

et al. 2006

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We investigated the immunogenicity of gonococcal transferrin binding protein B (TbpB) expressed with and without a eukaryotic secretion signal from a nonpropagating Venezuelan equine encephalitis virus replicon particle (VRP) delivery system. TbpB was successfully expressed in baby hamster kidney (BHK) cells, and the presence of the eukaryotic secretion signal not only apparently increased the protein's expression but also allowed for extracellular localization and glycosylation. Mice immunized with VRPs produced significant amounts of serum antibody although less than the amounts produced by mice immunized with recombinant protein. The response of mice immunized with VRPs encoding TbpB was consistently more Th1 biased than the response of mice immunized with recombinant protein alone. Boosting with recombinant protein following immunization with TbpB VRPs resulted in higher specific-antibody levels without altering the Th1/Th2 bias. Most of the immunization groups produced significant specific antibody binding to the intact surface of the homologous Neisseria gonorrhoeae strain. Immunization with TbpB VRPs without a eukaryotic secretion signal generated no measurable specific antibodies on the genital mucosal surface, but inclusion of a eukaryotic secretion signal or boosting with recombinant protein resulted in specific immunoglobulin G (IgG) and IgA in mucosal secretions after TbpB VRP immunization. The TbpB VRP system has potential for an N. gonorrhoeae vaccine.

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“…Virus replicon particles (VRPs) are defective nonpropagating VEE particles developed by Pushko et al in 1997 (60). VRPs have been used successfully and safely in immunization and challenge studies for a wide range of viral and bacterial pathogens in animal model systems (2,4,24,28,29,36,43,59,60,63,69,71). More importantly, these particles induce mucosal immune responses after nonmucosal inoculation in animals (18,28) and confer protection to the primary mucosal target tissue (25; E. M. Richmond, K. W. Brown, N. L. Davis, and R. E. Johnston, unpublished results).…”

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confidence: 99%

Venezuelan Equine Encephalitis Virus Replicon Particles Encoding Respiratory Syncytial Virus Surface Glycoproteins Induce Protective Mucosal Responses in Mice and Cotton Rats

Mok

Lee

Utley

et al. 2007

J Virol

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Respiratory syncytial virus (RSV) is an important viral pathogen that causes severe lower respiratory tract infection in infantsRespiratory syncytial virus (RSV) is a major human pathogen that causes serious lower respiratory tract illness in infants and the elderly. Significant morbidity and mortality for RSV are especially common in certain high-risk pediatric populations such as premature infants and infants with congenital heart or lung disorders. RSV bronchiolitis in infants is associated with recurrent wheezing and asthma later in childhood (53, 76). There are currently no FDA-approved vaccines for prevention of RSV disease by active immunization. Immunoprophylaxis by passive transfer of a humanized murine RSV fusion (F) protein-specific antibody is licensed for much of the high-risk infant population but is not cost-effective in otherwise healthy infants, who represent the majority of those hospitalized with RSV. There is also a high rate of RSV reinfection during childhood, which suggests that a protective immune response to a vaccine may need to differ either quantitatively or qualitatively from that induced by natural infection.Previous attempts to develop RSV vaccines have faced significant obstacles. An experimental formalin-inactivated RSV vaccine in the 1960s induced exacerbated disease and death in some vaccinated children during subsequent natural infection. It was shown subsequently that the formalin-inactivated RSV vaccine induced serum antibodies with poor neutralizing activity in infants (50) and an atypical Th2-biased T-cell response associated with enhanced histopathology following experimental immunization in small animals (58, 68). Treatment of RSV antigens with formaldehyde modifies the protein with carbonyl groups, which preferentially induces Th2-type responses and leads to enhanced disease (47). Other attempts to generate RSV vaccines include using live-attenuated cold-adapted, temperature-sensitive mutant strains of RSV (10, 12-17, 22, 32, 39, 41, 42), protein subunit vaccines coupled with adjuvant (30,56,70,73), and RSV proteins expressed from recombinant viral vectors, including vaccinia virus (52, 75), adenovirus (31), vesicular stomatitis virus (37), Semliki Forest virus (8), bovine/ human parainfluenza virus type 3 (26), Sendai virus (64), and Newcastle disease virus (45). Although some of these vaccines showed promising preclinical data, no vaccine has been licensed for human use due to safety concerns and lack of efficacy data. RSV vaccines under development have not been

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Evaluation of Venezuelan Equine Encephalitis (VEE) replicon-based Outer surface protein A (OspA) vaccines in a tick challenge mouse model of Lyme disease

Cited by 14 publications

References 29 publications

Distinct Contributions of Vaccine-Induced Immunoglobulin G1 (IgG1) and IgG2a Antibodies to Protective Immunity against Influenza

Distinct Contributions of Vaccine-Induced Immunoglobulin G1 (IgG1) and IgG2a Antibodies to Protective Immunity against Influenza

Vaccination of Mice with Gonococcal TbpB Expressed In Vivo from Venezuelan Equine Encephalitis Viral Replicon Particles

Venezuelan Equine Encephalitis Virus Replicon Particles Encoding Respiratory Syncytial Virus Surface Glycoproteins Induce Protective Mucosal Responses in Mice and Cotton Rats

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