Evaluation of monophosphoryl lipid A as adjuvant for pulmonary delivered influenza vaccine

Patil, Harshad P.; Murugappan, Senthil; Veer, Wouter ter; Meijerhof, Tjarko; Haan, Aalzen de; Frijlink, Henderik W.; Wilschut, Jan; Hinrichs, Wouter L. J.; Huckriede, Anke

doi:10.1016/j.jconrel.2013.11.013

Cited by 43 publications

(44 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the majority of the currently available influenza vaccines are administered via intramuscular or subcutaneous injection [5]. Injected vaccines generate strong systemic immunity but minimal mucosal immunity [6,7]. Moreover, injected vaccines can cause local reactions including pain, swelling and redness at the injection site, needle phobia, and transmission of infectious diseases due to needle stick injuries.…”

Section: Introductionmentioning

confidence: 99%

Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Tomar

Patil

Bracho

et al. 2018

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

Administration of influenza vaccines via the respiratory tract has potential benefits over conventional parenteral administration, inducing immunity directly at the site of influenza exposure as well as being needle free. In this study, we investigated the suitability of Advax™, a stable particulate polymorph of inulin, also referred to as delta inulin, as a mucosal adjuvant for whole inactivated influenza vaccine (WIV) administered either as a liquid or dry powder formulation. Spray freeze-drying produced Advax-adjuvanted WIV powder particles in a size range (1-5 μm) suitable for inhalation. The physical and biological characteristics of both WIV and Advax remained unaltered both by admixing WIV with Advax and by spray freeze drying. Upon intranasal or pulmonary immunization, both liquid and dry powder formulations containing Advax induced significantly higher systemic, mucosal and cellular immune responses than non-adjuvanted WIV formulations. Furthermore, pulmonary immunization with Advax-adjuvanted WIV led to robust memory B cell responses along with an increase of lung localization factors i.e. CXCR3, CD69, and CD103. A less pronounced but still positive effect of Advax was seen on memory T cell responses. In contrast to animals immunized with WIV alone, all animals pulmonary immunized with a single dose of Advax-adjuvanted WIV were fully protected with no visible clinical symptoms against a lethal dose of influenza virus. These data confirm that Advax is a potent mucosal adjuvant that boosts vaccine-induced humoral and cellular immune responses both in the lung and systemically with major positive effects on B-cell memory and complete protection against live virus. Hence, respiratory tract immunization, particularly via the lungs, with Advax-adjuvanted WIV formulation as a liquid or dry powder is a promising alternative to parenteral influenza vaccination.

show abstract

Section: Introductionmentioning

confidence: 99%

Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Tomar

Patil

Bracho

et al. 2018

Journal of Controlled Release

Self Cite

View full text Add to dashboard Cite

show abstract

“…A more balanced Th1/Th2 vaccine response is preferred as the combination of cellular with humoral immunity protects the host better against invading influenza viruses (Huber et al, 2006). Furthermore, although pulmonary influenza vaccines elicit local immune responses in the respiratory tract, their ability to induce intranasal IgA antibody titers are only modest (Audouy et al, 2011;Murugappan et al, 2013;Patil et al, 2014). A strong mucosal response in the nose and lungs is desired to provide maximal protection at the port of entry for the influenza virus (Renegar et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant

Murugappan

Frijlink

Petrovsky

et al. 2015

European Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

“…TLR agonists are already in practical use as adjuvants for a range of vaccines against viruses and other infections. The TLR4 agonist MPLA is used as an adjuvant for the malaria vaccine (25), and its use in animal models as a booster for influenza (26) and HIV (27) vaccines, as well as its direct effects in a model of P. aeruginosa cutaneous-burn infection and bacteremia (13), has also been reported. Furthermore, we recently reported that UT12 inoculation improved the prognosis for secondary bacterial pneumonia following influenza (15).…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Agonistic Antibody Promotes Host Defense against Chronic Pseudomonas aeruginosa Lung Infection in Mice

Nakamura

Iwanaga

Seki³

et al. 2016

Infect Immun

View full text Add to dashboard Cite

f Chronic lower respiratory tract infection with Pseudomonas aeruginosa is difficult to treat due to enhanced antibiotic resistance and decreased efficacy of drug delivery to destroyed lung tissue. To determine the potential for restorative immunomodulation therapies, we evaluated the effect of Toll-like receptor 4 (TLR4) stimulation on the host immune response to Pseudomonas infection in mice. We implanted sterile plastic tubes precoated with P. aeruginosa in the bronchi of mice, administered the TLR4/ MD2 agonistic monoclonal antibody UT12 intraperitoneally every week, and subsequently analyzed the numbers of viable bacteria and inflammatory cells and the levels of cytokines. We also performed flow cytometry-based phagocytosis and opsonophagocytic killing assays in vitro using UT12-treated murine peritoneal neutrophils. UT12-treated mice showed significantly enhanced bacterial clearance, increased numbers of Ly6G ؉ neutrophils, and increased concentrations of macrophage inflammatory protein 2 (MIP-2) in the lungs (P < 0.05). Depletion of CD4 ؉ T cells eliminated the ability of the UT12 treatment to improve bacterial clearance and promote neutrophil recruitment and MIP-2 production. Additionally, UT12-pretreated peritoneal neutrophils exhibited increased opsonophagocytic killing activity via activation of the serine protease pathway, specifically neutrophil elastase activity, in a TLR4-dependent manner. These data indicated that UT12 administration significantly augmented the innate immune response against chronic bacterial infection, in part by promoting neutrophil recruitment and bactericidal function. Pseudomonas aeruginosa is extremely difficult to eradicate once established in the lower respiratory tract (LRT) during chronic respiratory infection. Poor penetration of antibiotics into purulent airway secretions due to lung structure damage, acquired antibiotic resistance, defects in mucosal defenses, and the interference of bacterium-produced biofilms with phagocytic killing impede treatment (1). Chronic P. aeruginosa infection also represents an independent risk factor for accelerated loss of pulmonary function and decreased survival (2, 3).Lipopolysaccharide (LPS) is a glycolipid component of the Gram-negative bacterial cell wall that is recognized by Toll-like receptor 4 (TLR4), which induces various host responses, including proinflammatory cytokine production, and has known immunomodulatory properties (4). Priming with LPS has been shown to improve murine responses to bacterial infections (5-7), and prior LPS exposure attenuates proinflammatory cytokine production in response to LPS or bacterial challenge, a phenomenon that has historically been referred to as endotoxin tolerance (8, 9). Several immunomodulators, such as the TLR4 agonist monophosphoryl lipid A (MPLA), promote host immunity and are used as vaccine adjuvants for humans (10). In animal models, MPLA enhances the action of macrophages, B cells, and other antigenpresenting cells and promotes the differentiation of Th1 and Th2 cells from naïv...

show abstract

Evaluation of monophosphoryl lipid A as adjuvant for pulmonary delivered influenza vaccine

Cited by 43 publications

References 42 publications

Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Advax augments B and T cell responses upon influenza vaccination via the respiratory tract and enables complete protection of mice against lethal influenza virus challenge

Enhanced pulmonary immunization with aerosolized inactivated influenza vaccine containing delta inulin adjuvant

Toll-Like Receptor 4 Agonistic Antibody Promotes Host Defense against Chronic Pseudomonas aeruginosa Lung Infection in Mice

Contact Info

Product

Resources

About