tetano
Editor, Senior Moderator
Bioconjug Chem. 2019 Nov 18. doi: 10.1021/acs.bioconjchem.9b00644. [Epub ahead of print] [h=1]Cross-Protective Abilities of Hyaluronic Acid Modified with Tetraglycine-l-octaarginine as a Mucosal Adjuvant against Infection with Heterologous Influenza Viruses.[/h]
Tanishita S[SUP]1[/SUP], Ukawa M[SUP]1[/SUP], Tomono T[SUP]1[/SUP], Yoshida Y[SUP]1[/SUP], Tsujioka T[SUP]1[/SUP], Miyata K[SUP]2[/SUP], Tobita E[SUP]2[/SUP], Uto T[SUP]3[/SUP], Baba M[SUP]4[/SUP], Sakuma S[SUP]1[/SUP].
[h=3]Author information[/h] 1 Faculty of Pharmaceutical Sciences , Setsunan University , 45-1, Nagaotoge-cho , Hirakata, Osaka 573-0101 , Japan. 2 Life Science Materials Laboratory , ADEKA Company, Limited , 7-2-34, Higashiogu , Arakawa-ku, Tokyo 116-8553 , Japan. 3 Faculty of Medicine , University of Miyazaki , Kihara 5200, Kiyotake , Miyazaki 889-1692 , Japan. 4 Division of Antiviral Chemotherapy, Joint Research Center for Human Retrovirus Infection , Kagoshima University , 8-35-1, Sakuragaoka , Kagoshima 890-8544 , Japan.
[h=3]Abstract[/h] Mucosal vaccination, which secretion of immunoglobulin A (IgA) on the mucosa is accompanied by induction of immunoglobulin G (IgG) in the blood, is one of the most effective ways to circumvent influenza epidemics caused by incorrect prediction of epidemic viral strains or viral mutation. Secreted IgA is expected to prevent hosts from being infected with heterologous viruses because this antibody cross-reacts to strains other than those used for immunization. Our previous mouse experiments revealed that intranasal IgA with cross-reactivity was induced through nasal inoculation with inactivated whole viral particles of the H1N1 A/New Caledonia/20/99 IVR116 (NCL) strain in the presence of hyaluronic acid modified with tetraglycine-l-octaarginine. In the present study, heterologous influenza virus challenge was performed to validate a potential of the hyaluronic acid derivative as a mucosal adjuvant with cross-protective abilities. Serious weight loss was observed when mice were nasally inoculated with inactivated NCL viruses alone and subsequently exposed to mouse-adapted infectious viruses of the H1N1 A/Puerto Rico/8/34 (PR8) strain. The symptom associated with virus infection was hardly ever observed for mice inoculated with a mixture of the viral antigens and tetraglycine-l-octaarginine-linked hyaluronic acid, presumably due to high induction of IgG and IgA capable of cross-reacting to PR8 viruses. Less proliferation of PR8 viruses in those mice was also supported by an insignificant elevation of antibody levels through virus exposure. Our polysaccharide derivative enabled hosts to acquire adaptive immunity with cross-protective abilities against heterologous virus infection.
PMID: 31738536 DOI: 10.1021/acs.bioconjchem.9b00644
Tanishita S[SUP]1[/SUP], Ukawa M[SUP]1[/SUP], Tomono T[SUP]1[/SUP], Yoshida Y[SUP]1[/SUP], Tsujioka T[SUP]1[/SUP], Miyata K[SUP]2[/SUP], Tobita E[SUP]2[/SUP], Uto T[SUP]3[/SUP], Baba M[SUP]4[/SUP], Sakuma S[SUP]1[/SUP].
[h=3]Author information[/h] 1 Faculty of Pharmaceutical Sciences , Setsunan University , 45-1, Nagaotoge-cho , Hirakata, Osaka 573-0101 , Japan. 2 Life Science Materials Laboratory , ADEKA Company, Limited , 7-2-34, Higashiogu , Arakawa-ku, Tokyo 116-8553 , Japan. 3 Faculty of Medicine , University of Miyazaki , Kihara 5200, Kiyotake , Miyazaki 889-1692 , Japan. 4 Division of Antiviral Chemotherapy, Joint Research Center for Human Retrovirus Infection , Kagoshima University , 8-35-1, Sakuragaoka , Kagoshima 890-8544 , Japan.
[h=3]Abstract[/h] Mucosal vaccination, which secretion of immunoglobulin A (IgA) on the mucosa is accompanied by induction of immunoglobulin G (IgG) in the blood, is one of the most effective ways to circumvent influenza epidemics caused by incorrect prediction of epidemic viral strains or viral mutation. Secreted IgA is expected to prevent hosts from being infected with heterologous viruses because this antibody cross-reacts to strains other than those used for immunization. Our previous mouse experiments revealed that intranasal IgA with cross-reactivity was induced through nasal inoculation with inactivated whole viral particles of the H1N1 A/New Caledonia/20/99 IVR116 (NCL) strain in the presence of hyaluronic acid modified with tetraglycine-l-octaarginine. In the present study, heterologous influenza virus challenge was performed to validate a potential of the hyaluronic acid derivative as a mucosal adjuvant with cross-protective abilities. Serious weight loss was observed when mice were nasally inoculated with inactivated NCL viruses alone and subsequently exposed to mouse-adapted infectious viruses of the H1N1 A/Puerto Rico/8/34 (PR8) strain. The symptom associated with virus infection was hardly ever observed for mice inoculated with a mixture of the viral antigens and tetraglycine-l-octaarginine-linked hyaluronic acid, presumably due to high induction of IgG and IgA capable of cross-reacting to PR8 viruses. Less proliferation of PR8 viruses in those mice was also supported by an insignificant elevation of antibody levels through virus exposure. Our polysaccharide derivative enabled hosts to acquire adaptive immunity with cross-protective abilities against heterologous virus infection.
PMID: 31738536 DOI: 10.1021/acs.bioconjchem.9b00644