Liposomal gD ectodomain (gD1–306) vaccine protects against HSV2 genital or rectal infection of female and male mice

Olson, Kjerstie; Macias, P.; Hutton, Sally; Ernst, William; Fujii, Gary; Adler-Moore, Jill

doi:10.1016/j.vaccine.2009.09.120

Cited by 16 publications

(9 citation statements)

References 54 publications

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“…Additionally, we have shown the importance of having an optimal MPLA concentration (likely ranging between 12.5 and 25 μg/dose) in VesiVax liposomes and of its role in inducing central memory T cells and germinal center B cells. These results are consistent with our vaccination studies on influenza virus [ 76 , 77 ] and herpes simplex virus 2 [ 78 ]. To confirm these findings, further studies with a higher vertebrate model are warranted.…”

Section: Discussionsupporting

confidence: 93%

A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV

Poteet

Lewis

et al. 2015

PLoS ONE

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HIV virus-like particles (VLPs) present the HIV envelope protein in its native conformation, providing an ideal vaccine antigen. To enhance the immunogenicity of the VLP vaccine, we sought to improve upon two components; the route of administration and the additional adjuvant. Using HIV VLPs, we evaluated sub-cheek as a novel route of vaccine administration when combined with other conventional routes of immunization. Of five combinations of distinct prime and boost sequences, which included sub-cheek, intranasal, and intradermal routes of administration, intranasal prime and sub-cheek boost (IN+SC) resulted in the highest HIV-specific IgG titers among the groups tested. Using the IN+SC regimen we tested the adjuvant VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) + monophosphoryl lipid A (MPLA) at MPLA concentrations of 0, 7.5, 12.5, and 25 μg/dose in combination with our VLPs. Mice that received 12.5 or 25 μg/dose MPLA had the highest concentrations of Env-specific IgG2c (20.7 and 18.4 μg/ml respectively), which represents a Th1 type of immune response in C57BL/6 mice. This was in sharp contrast to mice which received 0 or 7.5 μg MPLA adjuvant (6.05 and 5.68 μg/ml of IgG2c respectively). In contrast to IgG2c, MPLA had minor effects on Env-specific IgG1; therefore, 12.5 and 25 μg/dose of MPLA induced the optimal IgG1/IgG2c ratio of 1.3. Additionally, the percentage of germinal center B cells increased significantly from 15.4% in the control group to 31.9% in the CALV + 25 μg MPLA group. These mice also had significantly more IL-2 and less IL-4 Env-specific CD8+ T cells than controls, correlating with an increased percentage of Env-specific central memory CD4+ and CD8+ T cells. Our study shows the strong potential of IN+SC as an efficacious route of administration and the effectiveness of VLPs combined with MPLA adjuvant to induce Env specific Th1-oriented HIV-specific immune responses.

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Section: Discussionsupporting

confidence: 93%

A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV

Poteet

Lewis

et al. 2015

PLoS ONE

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“…Sex-based differences in innate and adaptive immunity can contribute to the variances observed among males and females in severity of autoimmune diseases and cancers as well as altered response to infectious diseases and vaccines 34 - 36 . Of particular interest, in a rectal model of HSV-2 infection in mice, BALB/c male and female mice showed the same disease progression, whereas the female C57BL/6 mice were very resistant to HSV-2 infection and showed minimal signs of neurological disease 37 . In contrast, in a nonhuman primate model of rectal SHIV-1 infection, the females progressed faster to disease than their male counterparts, which was linked to an earlier and more robust inflammatory immune response in the rectum of the females, as well as increased expansion of Proteobacteria in their rectal mucosa 38 .…”

Section: Discussionmentioning

confidence: 99%

B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection

et al. 2018

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Determining the magnitude of local immune response during mucosal exposure to viral pathogens is critical to understanding the mechanism of viral pathogenesis. We previously showed that vaginal inoculation of lymphocytic choriomeningitis virus (LCMV) fails to induce a robust innate immune response in the lower female reproductive tract (FRT), allowing high titer viral replication and a delay in T cell-mediated viral control. Despite this immunological delay, LCMV replication remained confined mainly to the FRT and the draining iliac lymph node. Here, we show that rectal infection with LCMV triggers type I/III interferon responses, followed by innate immune activation and lymphocyte recruitment to the colon. In contrast to vaginal exposure, innate immunity controls LCMV replication in the colon, but virus rapidly disseminates systemically. Virus-induced inflammation promotes the recruitment of LCMV target cells to the colon followed by splenic viral dissemination by infected B cells, and to a lesser extent by CD8 T cells. These findings demonstrate major immunological differences between vaginal and rectal exposure to the same viral pathogen, highlighting unique risks associated with each of these common routes of sexual viral transmission.

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“…Immediately prior to use, lyophilized ORF5a protein was suspended in phosphate buffered saline (PBS) and emulsified in an equal volume of two different adjuvant preparations; (a) incomplete Freund’s adjuvant (IFA) (Sigma-Aldrich, St. Louis, MO), and (b) equal volumes of IFA and a liposome preparation containing monophosphoryl lipid A (MPL) (Ernst et al, 2006) (Molecular Express Inc., Rancho Dominguez, CA) using the double-hubbed needle method (Berlin and McKinney, 1958; Freund and Thomson, 1945). MPL is a low-toxicity derivative of lipopolysaccharide, a TLR4 agonist, shown in other systems to aid robust adaptive immune responses without the proinflammatory activity of LPS (Ernst et al, 2006; Mato-Haro et al, 2007; Olson et al, 2010). The dose of synthetic ORF5a in 1 ml preparations for each of the three immunizations at day 0, 10 and 20 of the study was 50 ug, 20 ug and 200 ug respectively per pig.…”

Section: Methodsmentioning

confidence: 99%

Immune response to ORF5a protein immunization is not protective against porcine reproductive and respiratory syndrome virus infection

Robinson

Figueiredo

Abrahante

et al. 2013

Veterinary Microbiology

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Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped RNA virus responsible for PRRS in swine, a disease with globally significant animal welfare and economic concerns. There is no specific treatment and variably effective immune protection. Molecular mechanisms responsible for virulence, pathogenesis and protective immune response remain poorly understood. These factors limit progress towards development of effective measures for prevention and treatment of PRRS. A novel PRRSV ORF5a protein, encoded in an open reading frame (ORF) that overlaps the major envelope glycoprotein GP5 ORF, was recently identified. Because ORF5a is highly conserved in diverse PRRSV isolates, is a structural protein in the virion, and elicits a specific antibody response in infected pigs, we investigated its potential role in immune protection against PRRSV infection. Pigs immunized with ORF5a protein had robust serologic responses. However, the antibodies did not neutralize virus, and immunity did not protect against challenge infection. We conclude from these findings that the ORF5a antibody response is neither neutralizing nor protective.

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Liposomal gD ectodomain (gD1–306) vaccine protects against HSV2 genital or rectal infection of female and male mice

Cited by 16 publications

References 54 publications

A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV

A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV

B cells are the predominant mediators of early systemic viral dissemination during rectal LCMV infection

Immune response to ORF5a protein immunization is not protective against porcine reproductive and respiratory syndrome virus infection

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