scholarly journals Formulation with CpG Oligodeoxynucleotides Prevents Induction of Pulmonary Immunopathology following Priming with Formalin-Inactivated or Commercial Killed Bovine Respiratory Syncytial Virus Vaccine

2005 ◽  
Vol 79 (4) ◽  
pp. 2024-2032 ◽  
Author(s):  
M. Oumouna ◽  
J. W. Mapletoft ◽  
B. C. Karvonen ◽  
L. A. Babiuk ◽  
S. van Drunen Littel-van den Hurk
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Virus Production ◽  
Neutralizing Antibody ◽  
Bovine Respiratory Syncytial Virus ◽  
Interleukin 4 ◽  
Cpg Odn ◽  
Cpg Oligodeoxynucleotides ◽  
Syncytial Virus

ABSTRACT Commercial killed bovine respiratory syncytial virus (K-BRSV) and formalin-inactivated BRSV (FI-BRSV) tend to induce Th2-type immune responses, which may not be protective and may even be detrimental during subsequent exposure to the virus. In this study we assessed the ability of CpG oligodeoxynucleotides (ODNs) to aid in the generation of effective and protective BRSV-specific immune responses. Mice were immunized subcutaneously with FI-BRSV formulated with CpG ODN, Emulsigen (Em), CpG ODN and Em, or non-CpG ODN and Em. Two additional groups were immunized with K-BRSV or K-BRSV and CpG ODN. After two vaccinations, the mice were challenged with BRSV. FI-BRSV induced Th2-biased immune responses characterized by production of serum immunoglobulin G1 (IgG1) and IgE, as well as interleukin-4 (IL-4), by in vitro-restimulated splenocytes. Formulation of FI-BRSV with CpG ODN, but not with non-CpG ODN, enhanced serum IgG2a and IFN-γ production by splenocytes, whereas serum IgE was reduced. Although the immune response induced by K-BRSV was not as strongly Th2 biased, the addition of CpG ODN to this commercial vaccine also resulted in a more Th1-type response. Furthermore, the addition of CpG ODN to the BRSV vaccine formulations resulted in enhanced neutralizing antibody responses. Significant production of IL-5, eotaxin, and eosinophilia was observed in the lungs of FI-BRSV- and K-BRSV-immunized mice. However, IL-5 and eotaxin levels, as well as the number of eosinophils, were decreased in the mice vaccinated with the CpG ODN-formulated vaccines. Finally, when formulated with CpG ODN, both FI-BRSV and K-BRSV significantly reduced virus production after challenge with BRSV.

scholarly journals Immunoprotective Activity and Safety of a RespiratorySyncytial Virus Vaccine: Mucosal Delivery of Fusion Glycoprotein with aCpG OligodeoxynucleotideAdjuvant

2003 ◽  
Vol 77 (24) ◽  
pp. 13156-13160 ◽  
Author(s):  
Gregory A. Prince ◽  
James J. Mond ◽  
David D. Porter ◽  
Kevin C. Yim ◽  
Steve J. Lan ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibody ◽  
Live Virus ◽  
Cotton Rat ◽  
F Protein ◽  
Virus Challenge ◽  
Cpg Oligodeoxynucleotides ◽  
Cotton Rats ◽  
Syncytial Virus

ABSTRACT CpG oligodeoxynucleotides (ODN) were identified that stimulated immunoglobulin production and cell proliferation in cotton rat cells in vitro. Three of these ODN were used as a mucosal adjuvant in the noses of cotton rats immunized via this route with respiratory syncytial virus fusion (F) protein. The CpG ODN markedly increased the cotton rat humoral neutralizing-antibody response to respiratory syncytial virus. Such immunized animals had a marked reduction in the production of infectious virus after a live-virus challenge. Animals immunized with the combination of F protein and CpG developed enhanced pulmonary pathology consisting of alveolitis and interstitial pneumonitis after a live-virus challenge. Similar enhanced disease has been seen in cotton rats and children immunized with formalin-inactivated respiratory syncytial virus.

scholarly journals Intranasal Immunization of Mice with a Bovine Respiratory Syncytial Virus Vaccine Induces Superior Immunity and Protection Compared to Those by Subcutaneous Delivery or Combinations of Intranasal and Subcutaneous Prime-Boost Strategies

2009 ◽  
Vol 17 (1) ◽  
pp. 23-35 ◽  
Author(s):  
John W. Mapletoft ◽  
Laura Latimer ◽  
Lorne A. Babiuk ◽  
Sylvia van Drunen Littel-van den Hurk
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Virus Replication ◽  
Vaccination Strategy ◽  
Bovine Respiratory Syncytial Virus ◽  
Mucosal Vaccine ◽  
Intranasal Delivery ◽  
Cpg Odn ◽  
Cpg Oligodeoxynucleotide ◽  
Syncytial Virus

ABSTRACT Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory mucosa, so it is desirable to develop a vaccination strategy that induces mucosal immunity. To achieve this, various delivery routes were compared for formalin-inactivated (FI) BRSV formulated with CpG oligodeoxynucleotide (ODN) and polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior to subcutaneous delivery in terms of antibody, cell-mediated, and mucosal immune responses, as well as reduction in virus replication after BRSV challenge. Although intranasal delivery of FI-BRSV also induced higher serum and lung antibody titers and gamma interferon (IFN-γ) production in the lungs than intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no significant differences were observed in cell-mediated immune responses or virus replication in the lungs of challenged mice. Interleukin 5 (IL-5), eotaxin, and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of the intranasal and subcutaneous routes. These results suggest that two intranasal immunizations with FI-BRSV formulated with CpG ODN and PP are effective and safe as an approach to induce systemic and mucosal responses, as well to reduce virus replication after BRSV challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime-boost strategies were also safe and almost as efficacious. In addition to the implications for the development of a protective BRSV vaccine for cattle, formulation with CpG ODN and PP could also prove important in the development of a mucosal vaccine that induces protective immunity against human RSV.

scholarly journals Formulation of bovine respiratory syncytial virus fusion protein with CpG oligodeoxynucleotide, cationic host defence peptide and polyphosphazene enhances humoral and cellular responses and induces a protective type 1 immune response in mice

2009 ◽  
Vol 90 (8) ◽  
pp. 1892-1905 ◽  
Author(s):  
J. Kovacs-Nolan ◽  
J. W. Mapletoft ◽  
Z. Lawman ◽  
L. A. Babiuk ◽  
S. van Drunen Littel-van den Hurk
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Fusion Protein ◽  
Vaccine Development ◽  
Host Defence ◽  
Cpg Odn ◽  
Cpg Oligodeoxynucleotides ◽  
Cpg Oligodeoxynucleotide ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the leading cause of serious respiratory tract disease in children and calves; however, RSV vaccine development has been slow due to early observations that formalin-inactivated vaccines induced Th2-type immune responses and led to disease enhancement upon subsequent exposure. Hence, there is a need for novel adjuvants that will promote a protective Th1-type or balanced immune response against RSV. CpG oligodeoxynucleotides (ODNs), indolicidin, and polyphosphazene were examined for their ability to enhance antigen-specific immune responses and influence the Th-bias when co-formulated with a recombinant truncated bovine RSV (BRSV) fusion protein (ΔF). Mice immunized with ΔF co-formulated with CpG ODN, indolicidin, and polyphosphazene (ΔF/CpG/indol/PP) developed higher levels of ΔF-specific serum IgG, IgG1 and IgG2a antibodies when compared with ΔF alone, and displayed an increase in the frequency of gamma interferon-secreting cells and decreased interleukin (IL)-5 production by in vitro restimulated splenocytes, characteristic of a Th1 immune response. These results were observed in both C57BL/6 and BALB/c strains of mice. When evaluated in a BRSV challenge model, mice immunized with ΔF/CpG/indol/PP developed significantly higher levels of BRSV-neutralizing serum antibodies than mice immunized with the ΔF protein alone, and displayed significantly less pulmonary IL-4, IL-5, IL-13 and eotaxin and reduced eosinophilia after challenge. These results suggest that co-formulation of ΔF with CpG ODN, host defence peptide and polyphosphazene may result in a safe and effective vaccine for the prevention of BRSV and may have implications for the development of novel human RSV vaccines.

Effects of dual vaccination for bovine respiratory syncytial virus and Haemophilus somnus on immune responses

Vaccine ◽  
2006 ◽  
Vol 24 (33-34) ◽  
pp. 6018-6027 ◽  
Author(s):  
L BERGHAUS ◽  
L CORBEIL ◽  
R BERGHAUS ◽  
W KALINA ◽  
R KIMBALL ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Bovine Respiratory Syncytial Virus ◽  
Haemophilus Somnus ◽  
Syncytial Virus

scholarly journals Enhancement of Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus

2003 ◽  
Vol 77 (6) ◽  
pp. 3615-3623 ◽  
Author(s):  
Sang-Moo Kang ◽  
Richard W. Compans
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 4 ◽  
Cpg Odn ◽  
Virus Like Particles ◽  
Cpg Oligodeoxynucleotides ◽  
Immunodeficiency Virus ◽  
Helper Cell Type ◽  
Spleen And Lymph Nodes

ABSTRACT Cholera toxin (CT) is the most potent known mucosal adjuvant, but its toxicity precludes its use in humans. Here, in an attempt to develop safe and effective mucosal adjuvants, we compared immune responses to simian immunodeficiency virus (SIV) virus-like particles (VLPs) after intranasal coimmunization with RANTES, CpG oligodeoxynucleotides (ODN), or CT. Antibody analysis demonstrated that RANTES and CpG ODN had capacities for mucosal adjuvanticity, i.e., for enhancing serum and vaginal antibodies specific to SIV Env, similar to those for CT. RANTES and CpG ODN skewed serum antibodies predominantly to the immunoglobulin G2a isotype. Most importantly, RANTES and CpG ODN were more effective than CT in increasing neutralizing titers of both serum and vaginal antibodies. After intranasal coadministration with VLPs, RANTES or CpG ODN also induced increased levels of gamma interferon (IFN-γ)-producing lymphocyte and cytotoxic T-lymphocyte activities in both spleen and lymph nodes but did not increase the levels of interleukin-4-producing lymphocytes. The results suggest that RANTES and CpG ODN enhance immune responses in a T-helper-cell-type-1 (Th1)-oriented manner and that they can be used as effective mucosal adjuvants for enhancing both humoral and cellular immune responses in the context of VLPs, which are particulate antigens.

scholarly journals Intranasal Immunization with Gal-Inhibitable Lectin plus an Adjuvant of CpG Oligodeoxynucleotides Protects against Entamoeba histolytica Challenge

2007 ◽  
Vol 75 (10) ◽  
pp. 4917-4922 ◽  
Author(s):  
Catherine P. A. Ivory ◽  
Kris Chadee
Keyword(s):  
Immune Responses ◽  
Entamoeba Histolytica ◽  
Mucosal Vaccine ◽  
Target Cells ◽  
Cpg Odn ◽  
Mucosal Vaccination ◽  
Humoral Immune ◽  
Cpg Oligodeoxynucleotides ◽  
Humoral Immune Responses

ABSTRACT The development of an effective amebiasis vaccine could improve child health in the developing world, reducing cases of amebic colitis and liver abscess. An ideal vaccine would be comprised of a well-characterized parasite antigen and an adjuvant, which would have high potency while driving the immune response in a Th1 direction. This study describes a mucosal vaccine composed of the Entamoeba histolytica galactose/N-acetyl-d-galactosamine-inhibitable lectin (Gal-lectin) and CpG oligodeoxynucleotides (CpG-ODN). The Gal-lectin is a protein involved in parasite virulence and adherence and is known to activate immune cells, while CpG-ODN are known to be potent inducers of type 1-like immune responses. We demonstrated that intranasal administration of the vaccine resulted in strong Gal-lectin-specific Th1 responses and humoral responses. Vaccination induced the production of Gal-lectin-specific T cells and the production of the proinflammatory cytokine gamma interferon. Vaccinated animals had detectable serum anti-Gal-lectin immunoglobulin G (IgG) and stool anti-Gal-lectin IgA capable of blocking parasite adherence to target cells in vitro. One week after immunization, gerbils were challenged intrahepatically with live trophozoites. Vaccinated gerbils had no detectable abscesses after day 5, whereas control gerbils developed larger abscesses. These results show that mucosal vaccination with Gal-lectin and CpG-ODN can induce both systemic and humoral immune responses.

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