scholarly journals The Immunogenicity of Capsid-Like Particle Vaccines in Combination with Different Adjuvants Using Different Routes of Administration

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 131
Author(s):  
Christoph M. Janitzek ◽  
Philip H. R. Carlsen ◽  
Susan Thrane ◽  
Vijansh M. Khanna ◽  
Virginie Jakob ◽  
...  
Keyword(s):  
Aluminum Hydroxide ◽  
Lipid A ◽  
Antibody Responses ◽  
Bacterial Protein ◽  
Adjuvant Effect ◽  
Water Emulsion ◽  
Routes Of Administration ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Vaccine Antigens

Capsid-like particle (CLP) displays can be used to enhance the immunogenicity of vaccine antigens, but a better understanding of how CLP vaccines are best formulated and delivered is needed. This study compared the humoral immune responses in mice elicited against two different vaccine antigens (a bacterial protein and a viral peptide) delivered on an AP205 CLP platform using six different adjuvant formulations. In comparison to antibody responses obtained after immunization with the unadjuvanted CLP vaccine, three of the adjuvant systems (neutral liposomes/monophosphoryl lipid A/quillaja saponaria 21, squalene-in-water emulsion, and monophosphoryl lipid A) caused significantly increased antibody levels, whereas formulation with the three other adjuvants (aluminum hydroxide, cationic liposomes, and cationic microparticles) resulted in similar or even decreased antibody responses. When delivering the soluble bacterial protein in a squalene-in-water emulsion, 4-log lower IgG levels were obtained compared to when the protein was delivered on CLPs without the adjuvant. The AP205 CLP platform promoted induction of both IgG1 and IgG2 subclasses, which could be skewed towards a higher production of IgG1 (aluminum hydroxide). Compared to other routes, intramuscular administration elicited the highest IgG levels. These results indicate that the effect of the external adjuvant does not always synergize with the adjuvant effect of the CLP display, which underscores the need for empirical testing of different extrinsic adjuvants.

scholarly journals Parenterally Administered Norovirus GII.4 Virus-Like Particle Vaccine Formulated with Aluminum Hydroxide or Monophosphoryl Lipid A Adjuvants Induces Systemic but Not Mucosal Immune Responses in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Suvi Heinimäki ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Aluminum Hydroxide ◽  
Mucosal Immunity ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Virus Like Particle ◽  
Iga Antibodies ◽  
Nasal Secretions ◽  
Sparing Effect ◽  
Norovirus Gii

Norovirus (NoV) is a main cause of acute gastroenteritis across all ages worldwide. NoV vaccine candidates currently in clinical trials are based on noninfectious highly immunogenic virus-like particles (VLPs) delivered intramuscularly (IM). Since NoV is an enteric pathogen, it is likely that mucosal immunity has a significant role in protection from infection in the intestine. Due to the fact that IM delivery of NoV VLPs does not generate mucosal immunity, we investigated whether NoV genotype GII.4 VLPs coadministered with aluminum hydroxide (Al(OH)3) or monophosphoryl lipid A (MPLA) would induce mucosal antibodies in mice. Systemic as well as mucosal IgG and IgA antibodies in serum and intestinal and nasal secretions were measured. As expected, strong serum IgG, IgG1, and IgG2a antibodies as well as a dose sparing effect were induced by both Al(OH)3and MPLA, but no mucosal IgA antibodies were detected. In contrast, IN immunization with GII.4 VLPs without an adjuvant induced systemic as well as mucosal IgA antibody response. These results indicate that mucosal delivery of NoV VLPs is needed for induction of mucosal responses.

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.

Immunogenicity of HPV and HBV vaccines: adjuvanticity of synthetic analogs of monophosphoryl lipid A combined with aluminum hydroxide

Apmis ◽  
2019 ◽  
Vol 127 (3) ◽  
pp. 150-157 ◽  
Author(s):  
Nastaran Taleghani ◽  
Ali Bozorg ◽  
Amin Azimi ◽  
Homa Zamani
Keyword(s):  
Aluminum Hydroxide ◽  
Lipid A ◽  
Synthetic Analogs ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

2009 ◽  
Vol 16 (5) ◽  
pp. 699-705 ◽  
Author(s):  
David I. Bernstein ◽  
Rhonda D. Cardin ◽  
Fernando J. Bravo ◽  
Jane E. Strasser ◽  
Nicholas Farley ◽  
...  
Keyword(s):  
Genital Herpes ◽  
Lipid A ◽  
Cationic Liposome ◽  
Antibody Responses ◽  
Dna Complexes ◽  
Adjuvant Activity ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Simplex Virus

ABSTRACT Development of a herpes simplex virus (HSV) vaccine is a priority because these infections are common. It appears that potent adjuvants will be required to augment the immune response to subunit HSV vaccines. Therefore, we evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant in a mouse model of genital herpes. Using a whole-virus vaccine (HVAC), we showed that the addition of CLDC improved antibody responses compared to vaccine alone. Most important, CLDC increased survival, reduced symptoms, and decreased vaginal virus replication compared to vaccine alone or vaccine administered with monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) following intravaginal challenge of mice. When CLDC was added to an HSV gD2 vaccine, it increased the amount of gamma interferon that was produced from splenocytes stimulated with gD2 compared to the amount produced with gD2 alone or with MPL-alum. The addition of CLDC to the gD2 vaccine also improved the outcome following vaginal HSV type 2 challenge compared to vaccine alone and was equivalent to vaccination with an MPL-alum adjuvant. CLDC appears to be a potent adjuvant for HSV vaccines and should be evaluated further.

scholarly journals Differential Immunogenicity and Protective Efficacy Elicited by MTO- and DMT-Adjuvanted CMFO Subunit Vaccines against Mycobacterium tuberculosis Infection

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Nadeem Ullah ◽  
Ling Hao ◽  
Yaqi Wu ◽  
Yandi Zhang ◽  
Qing Lei ◽  
...  
Keyword(s):  
Delivery System ◽  
Subunit Vaccine ◽  
Lipid A ◽  
Protective Efficacy ◽  
Protein Vaccine ◽  
Subunit Vaccines ◽  
Water Emulsion ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Oil In Water

Tuberculosis (TB) remains a major and global problem of public health. An effective TB subunit vaccine is urgently needed. Proper selection of the delivery system for the vaccine is crucial for inducing an appropriate immune response tailored to control the target pathogen. In this study, we compared the immunogenicity and protective efficacy of CMFO subunit vaccines against primary progressive TB in two different adjuvant systems: the MTO oil-in-water (O/W) emulsion composed of monophosphoryl lipid A (MPL), trehalose-6,60-dibehenate (TDB), and oil in water emulsion MF59 and the DMT liposome containing dimethyldioctadecylammonium bromide (DDA), monophosphoryl lipid A (MPL), and trehalose-6,60-dibehenate (TDB). Our results demonstrated that the DMT-adjuvanted CMFO could confer more significant protection against M. tuberculosis infection than the CMFO/MTO did in mice. In particular, the adjuvant DMT showed a stronger ability than the O/W emulsion to adjuvant CMFO subunit vaccine and enhanced protection, attributed to elicit Th1-biased responses, strong Th1/Th17 cytokine responses, and IFN-γ+ or IL-2+ T cell responses. Therefore, our findings demonstrate that the liposome delivery system shows more effectiveness to adjuvant TB subunit vaccine than O/W emulsion and highlight the importance of adjuvant formulation for the better efficacy of a protein vaccine.

scholarly journals Monophosphoryl lipid A behaves as a T-cell-independent type 1 carrier for hapten-specific antibody responses in mice.

1995 ◽  
Vol 63 (1) ◽  
pp. 168-174 ◽  
Author(s):  
K R Myers ◽  
P Beining ◽  
M Betts ◽  
H Snippe ◽  
J Inman ◽  
...  
Keyword(s):  
T Cell ◽  
Specific Antibody ◽  
Lipid A ◽  
Antibody Responses ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

scholarly journals Acellular and "low" pertussis vaccines: adverse events and the role of mutations

2009 ◽  
Vol 51 (3) ◽  
pp. 131-134 ◽  
Author(s):  
Hisako G. Higashi ◽  
Expedito Luna ◽  
Alexander R. Precioso ◽  
Marluce Vilela ◽  
Flávia S. Kubrusly ◽  
...  
Keyword(s):  
Adverse Events ◽  
Pertussis Vaccine ◽  
Lipid A ◽  
Production Capacity ◽  
Adjuvant Effect ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Dtp Vaccine ◽  
Main Components

Objective: to discuss the current PAHO recommendation that does not support the substitution of traditional cellular DTP vaccine by acellular DTP, and the role of mutations, in humans, as the main cause of rare adverse events, such as epileptic-like convulsions, triggered by pertussis vaccine. Data review: the main components related to toxic effects of cellular pertussis vaccines are the lipopolysaccharide of bacterial cell wall and pertussis toxin. The removal of part of lipopolysaccharide layer has allowed the creation of a safer cellular pertussis vaccine, with costs comparable to the traditional cellular vaccine, and which may be a substitute for the acellular vaccine. Conclusion: The new methodology introduced by Instituto Butantan allows for the development of a new safer pertussis vaccine with low LPS content (Plow), and the use of the lipopolysaccharide obtained in the process in the production of monophosphoryl lipid A. This component has shown potent adjuvant effect when administered together with influenza inactivated vaccine, making possible to reduce the antigen dose, enhancing the production capacity and lowering costs.

scholarly journals Lactoferrin-monophosphoryl lipid A complex enhances immunity of mice to Plesiomonas shigelloides CNCTC 138/92.

2008 ◽  
Vol 55 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Grzegorz Chodaczek ◽  
Michal Zimecki ◽  
Jolanta Lukasiewicz ◽  
Czesław Lugowski
Keyword(s):  
Immune Response ◽  
Lipid A ◽  
Adjuvant Effect ◽  
Plesiomonas Shigelloides ◽  
Monophosphoryl Lipid A ◽  
Specific Serum ◽  
Monophosphoryl Lipid ◽  
Serum Iga ◽  
Cellular Immune ◽  
Stimulation Of

Our previous study showed the efficacy of lactoferrin-monophosphoryl lipid A isolated from Hafnia alvei LPS complex (LF-MPL(H.a.)) as an adjuvant in stimulation of humoral and cellular immune response in mice to conventional antigens and a lower pyrogenicity of the complex as compared with MPL(H.a.) alone. In the present investigation we demonstrated that LF-MPL(H.a.) complex enhanced the immunity of BALB/c mice immunized with Plesiomonas shigelloides CNCTC 138/92 bacterial vaccine, against P. shigelloides infection. The adjuvant effect was evidenced by a significant increase of the antigen-specific serum IgG, IgG(2a), and IgG(1) and elevation of antigen-specific serum IgA concentrations. In addition, application of the adjuvant facilitated better clearance of the bacteria in spleens and livers of infected mice when compared with MPL(H.a.) alone. These features of the new adjuvant may predispose it for vaccination protocols in humans.

Sign in / Sign up

Export Citation Format

Share Document