The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

نویسندگان

  • Frank Wegmann
  • Amin E. Moghaddam
  • Torben Schiffner
  • Kate H. Gartlan
  • Timothy J. Powell
  • Rebecca A. Russell
  • Matthijs Baart
  • Emily W. Carrow
  • Quentin J. Sattentau
  • S. A. Plotkin
چکیده

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8(+) T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines

CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonst...

متن کامل

Protective Immunity in Mice Following Immunization with the Cochleate-Based Subunit Influenza Vaccines

High morbidity and mortality of influenza virus infection makes it an important disease world-wide. Mouse is a very well-studied animal model for this disease with similar manifestation to human disease. It would be desirable to induce mucosal as well as circulating immune responses to obtain protection from infection and to decrease the spread of the virus. Cell mediated immunity (proliferativ...

متن کامل

Heamagglutinin Conserved Domain (HA2) Prepared in Prokaryotic System is Immunogenic in Mice but not Protective against Lethal Influenza Challenge

Background and Aims: Influenza vaccine production process is time-consuming with little-to-no cross-protection which requires annual adjustment. The construction of a universal vaccine to deal with the pandemics and epidemics which occasionally threat human population is the aim of many researches worldwide. Today, influenza vaccines are mostly against two major antigenic proteins, hemagglutini...

متن کامل

Evaluation of immunogenicity of recombinant influenza nucleoprotein (NP) for universal vaccine

Background: Influenza vaccines based on conserved proteins are being developed persistently. The conserved protein vaccines based on Nucleoprotein (NP) are highly protected vaccines against influenza viruses that can be used as a Universal vaccine. Aluminum hydroxide (Alum) is the most common adjuvant used in vaccine formulation to improve immunization by altering the epitopes’ folds. However, ...

متن کامل

Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii

BBackground: We have previously reported that immunization with GRA 2 antigen of Toxoplasma gondii induces protective immunity in CBA /J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii. Metho...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 22  شماره 

صفحات  -

تاریخ انتشار 2015