scholarly journals Single and Combination Herpes Simplex Virus Type 2 Glycoprotein Vaccines Adjuvanted with CpG Oligodeoxynucleotides or Monophosphoryl Lipid A Exhibit Differential Immunity That Is Not Correlated to Protection in Animal Models

2011 ◽  
Vol 18 (10) ◽  
pp. 1702-1709 ◽  
Author(s):  
Tansi Khodai ◽  
Debbie Chappell ◽  
Clare Christy ◽  
Paul Cockle ◽  
Jim Eyles ◽  
...  
Keyword(s):  
T Cell ◽  
Animal Models ◽  
Guinea Pig ◽  
Lipid A ◽  
Neutralizing Antibody ◽  
T Cell Response ◽  
Cpg Oligodeoxynucleotides ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Ifn Γ

ABSTRACTDespite several attempts to develop an effective prophylactic vaccine for HSV-2, all have failed to show efficacy in the clinic. The most recent of these failures was the GlaxoSmithKline (GSK) subunit vaccine based on the glycoprotein gD with the adjuvant monophosphoryl lipid A (MPL). In a phase 3 clinical trial, this vaccine failed to protect from HSV-2 disease, even though good neutralizing antibody responses were elicited. We aimed to develop a superior, novel HSV-2 vaccine containing either gD or gB alone or in combination, together with the potent adjuvant CpG oligodeoxynucleotides (CPG). The immunogenic properties of these vaccines were compared in mice. We show that gB/CPG/alum elicited a neutralizing antibody response similar to that elicited by gD/CPG/alum vaccine but a significantly greater gamma interferon (IFN-γ) T cell response. Furthermore, the combined gB-gD/CPG/alum vaccine elicited significantly greater neutralizing antibody and T cell responses than gD/MPL/alum. The efficacies of these candidate vaccines were compared in the mouse and guinea pig disease models, including a novel male guinea pig genital disease model. These studies demonstrated that increased immune response did not correlate to improved protection. First, despite a lower IFN-γ T cell response, the gD/CPG/alum vaccine was more effective than gB/CPG/alum in mice. Furthermore, the gB-gD/CPG/alum vaccine was no more effective than gD/MPL/alum in mice or male guinea pigs. We conclude that difficulties in correlating immune responses to efficacy in animal models will act as a deterrent to researchers attempting to develop effective HSV vaccines.

scholarly journals Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

2017 ◽  
Vol 24 (3) ◽  
Author(s):  
Katharina Richard ◽  
Barbara J. Mann ◽  
Aiping Qin ◽  
Eileen M. Barry ◽  
Robert K. Ernst ◽  
...  
Keyword(s):  
Francisella Tularensis ◽  
Subunit Vaccine ◽  
Lipid A ◽  
Ex Vivo ◽  
The United States ◽  
Content Type ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Ifn Γ ◽  
Schu S4

ABSTRACT Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in the United States. Previously, we showed that incorporating lysates from partially attenuated F. tularensis LVS or fully virulent F. tularensis Schu S4 strains into catanionic surfactant vesicle (V) nanoparticles (LVS-V and Schu S4-V, respectively) protected fully against F. tularensis LVS intraperitoneal (i.p.) challenge in mice. However, we achieved only partial protection against F. tularensis Schu S4 intranasal (i.n.) challenge, even when employing heterologous prime-boost immunization strategies. We now extend these findings to show that both LVS-V and Schu S4-V immunization (i.p./i.p.) elicited similarly high titers of anti-F. tularensis IgG and that the titers could be further increased by adding monophosphoryl lipid A (MPL), a nontoxic Toll-like receptor 4 (TLR4) adjuvant that is included in several U.S. FDA-approved vaccines. LVS-V+MPL immune sera also detected more F. tularensis antigens than LVS-V immune sera and, after passive transfer to naive mice, significantly delayed the time to death against F. tularensis Schu S4 subcutaneous (s.c.) but not i.n. challenge. Active immunization with LVS-V+MPL (i.p./i.p.) also increased the frequency of gamma interferon (IFN-γ)-secreting activated helper T cells, IFN-γ production, and the ability of splenocytes to control intramacrophage F. tularensis LVS replication ex vivo. Active LVS-V+MPL immunization via heterologous routes (i.p./i.n.) significantly elevated IgA and IgG levels in bronchoalveolar lavage fluid and significantly enhanced protection against i.n. F. tularensis Schu S4 challenge (to ∼60%). These data represent a significant step in the development of a subunit vaccine against the highly virulent type A strains.

scholarly journals Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants for Mycobacterium tuberculosis Multivalent Acellular Vaccine

2005 ◽  
Vol 73 (1) ◽  
pp. 250-257 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Yolanta Fishman ◽  
Herve Bercovier
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lipid A ◽  
Protective Efficacy ◽  
Gamma Interferon ◽  
No Production ◽  
Adjuvant Effect ◽  
Recombinant Antigens ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Ifn Γ

ABSTRACT In this study, we examined the immunogenicity and protective efficacy of six immunodominant Mycobacterium tuberculosis recombinant antigens (85B, 38kDa, ESAT-6, CFP21, Mtb8.4, and 16kDa) in a multivalent vaccine preparation (6Ag). Gamma interferon (IFN-γ) and monophosphoryl lipid A-trehalose dicorynomycolate (Ribi) adjuvant systems were used separately or in combination for immunization with the recombinant antigens. Our results demonstrate that immunization of mice with Ribi emulsified antigens in the presence of IFN-γ (Ribi+6Ag+IFN-γ) resulted after challenge with a virulent M. tuberculosis strain in a significant reduction in the CFU counts that was comparable to that achieved with the BCG vaccine (∼0.9-log protection). Antigen-specific immunoglobulin G (IgG) titers in the Ribi+6Ag+IFN-γ-immunized mice were lower than in mice immunized with Ribi+6Ag and were oriented toward a Th1-type response, as confirmed by elevated IgG2a levels. In addition, splenocyte proliferation, IFN-γ secretion, and NO production were significantly higher in splenocytes derived from Ribi+6Ag+IFN-γ-immunized mice, whereas IL-10 secretion was decreased. These findings confirm the induction of a strong cellular immunity in the vaccinated mice that correlates well with their enhanced resistance to M. tuberculosis. The adjuvant effect of IFN-γ was dose dependent. A dose of 5 μg of IFN-γ per mouse per immunization gave optimal protection, whereas lower or higher amounts (0.5 or 50 μg/ mouse) of IFN-γ failed to enhance protection.

scholarly journals Promotion of Cellular and Humoral Immunity against Foot-and-Mouth Disease Virus by Immunization with Virus-Like Particles Encapsulated in Monophosphoryl Lipid A and Liposomes

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 633
Author(s):  
Woo Sik Kim ◽  
Yong Zhi ◽  
Huichen Guo ◽  
Eui-Baek Byun ◽  
Jae Hyang Lim ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Lipid A ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Virus Like Particles ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Foot And Mouth ◽  
Ifn Γ

Virus-like particles (VLPs) have emerged as promising vaccine candidates against foot-and-mouth disease (FMD). However, such vaccines provide a relatively low level of protection against FMD virus (FMDV) because of their poor immunogenicity. Therefore, it is necessary to design effective vaccine strategies that induce more potent immunogenicity. In order to investigate the means to improve FMD VLP vaccine (VLPFMDV) immunogenicity, we encapsulated VLPs (MPL/DDA-VLPFMDV) with cationic liposomes based on dimethyldioctadecylammonium bromide (DDA) and/or monophosphoryl lipid A (MPL, TLR4 agonist) as adjuvants. Unlike inactivated whole-cell vaccines, VLPFMDV were successfully encapsulated in this MPL/DDA system. We found that MPL/DDA-VLPFMDV could induce strong cell-mediated immune responses by inducing not only VLP-specific IFN-γ+CD4+ (Th1), IL-17A+CD4+ (Th17), and IFN-γ+CD8+ (activated CD8 response) T cells, but also the development of VLP-specific multifunctional CD4+ and CD8+ memory T cells co-expressing IFN-γ, TNF-α, and IL-2. In addition, the MPL/DDA-VLPFMDV vaccine markedly induced VLP-specific antibody titers; in particular, the vaccine induced greater Th1-predominant IgG responses than VLPFMDV only and DDA-VLPFMDV. These results are expected to provide important clues for the development of an effective VLPFMDV that can induce cellular and humoral immune responses, and address the limitations seen in current VLP vaccines for various diseases.

scholarly journals TLR4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A Differentially Regulate Effector and Memory CD8+ T Cell Differentiation

2014 ◽  
Vol 192 (9) ◽  
pp. 4221-4232 ◽  
Author(s):  
Weiguo Cui ◽  
Nikhil S. Joshi ◽  
Ying Liu ◽  
Hailong Meng ◽  
Steven H. Kleinstein ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Lipid A ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Memory Cd8 T Cell

scholarly journals Inactivation of suppressor T-cell activity by nontoxic monophosphoryl lipid A.

1988 ◽  
Vol 56 (5) ◽  
pp. 1076-1083 ◽  
Author(s):  
P J Baker ◽  
J R Hiernaux ◽  
M B Fauntleroy ◽  
B Prescott ◽  
J L Cantrell ◽  
...  
Keyword(s):  
T Cell ◽  
Lipid A ◽  
Cell Activity ◽  
Suppressor T Cell ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals Signature for Long-Term Vaccine-Mediated Control of a Simian and Human Immunodeficiency Virus 89.6P Challenge: Stable Low-Breadth and Low-Frequency T-Cell Response Capable of Coproducing Gamma Interferon and Interleukin-2

2005 ◽  
Vol 79 (6) ◽  
pp. 3243-3253 ◽  
Author(s):  
Shanmugalakshmi Sadagopal ◽  
Rama Rao Amara ◽  
David C. Montefiori ◽  
Linda S. Wyatt ◽  
Silvija I. Staprans ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Interleukin 2 ◽  
Neutralizing Antibody ◽  
Gamma Interferon ◽  
T Cell Response ◽  
Viral Control ◽  
Immunodeficiency Virus ◽  
Ifn Γ

ABSTRACT In 2001, we reported 20 weeks of control of challenge with the virulent 89.6P chimera of simian and human immunodeficiency viruses (SHIV-89.6P) by a Gag-Pol-Env vaccine consisting of DNA priming and modified vaccinia virus Ankara boosting. Here we report that 22 out of 23 of these animals successfully controlled their viremia until their time of euthanasia at 200 weeks postchallenge. At euthanasia, all animals had low to undetectable viral loads and normal CD4 counts. During the long period of viral control, gamma interferon (IFN-γ)-producing antiviral T cells were present at unexpectedly low breadths and frequencies. Most animals recognized two CD8 and one CD4 epitope and had frequencies of IFN-γ-responding T cells from 0.01 to 0.3% of total CD8 or CD4 T cells. T-cell responses were remarkably stable over time and, unlike responses in most immunodeficiency virus infections, maintained good functional characteristics, as evidenced by coproduction of IFN-γ and interleukin-2. Overall, high titers of binding and neutralizing antibody persisted throughout the postchallenge period. Encouragingly, long-term control was effective in macaques of diverse histocompatibility types.

Reversal of Age-Related Deficient Influenza Virus-Specific CTL Responses and IFN-γ Production by Monophosphoryl Lipid A

1996 ◽  
Vol 173 (1) ◽  
pp. 64-78 ◽  
Author(s):  
Innocent N. Mbawuike ◽  
Catherine Acuna ◽  
Diana Caballero ◽  
Khiem Pham-Nguyen ◽  
Brian Gilbert ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Age Related ◽  
Ifn Γ ◽  
Ctl Responses
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