Emulsified nanoparticles containing inactivated influenza virus and CpG oligodeoxynucleotides critically influences the host immune responses in mice.
BACKGROUND
Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.


RESULTS
After formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span(R)85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 microg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs) were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption)-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2).


CONCLUSIONS
Encapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a potential shortage of prophylactic vaccines against local infectious diseases, in particular pandemic influenza. Moreover, the cross-clade neutralizing antibody responses data verify the potential of such adjuvanted H5N1 candidate vaccine as an effective tool in pre-pandemic preparedness.
Huang
Ming-Hsi
MH
Vaccine Research and Development Center, National Health Research Institutes, Zhunan Town, Taiwan. huangminghsi@nhri.org.tw
Lin
Su-Chen
SC
Hsiao
Chia-Hsin
CH
Chao
Hsin-Ju
HJ
Yang
Hung-Ren
HR
Liao
Chien-Chun
CC
Chuang
Po-Wei
PW
Wu
Huang-Pi
HP
Huang
Chiung-Yi
CY
Leng
Chih-Hsiang
CH
Liu
Shih-Jen
SJ
Chen
Hsin-Wei
HW
Chou
Ai-Hsiang
AH
Hu
Alan Yung-Chih
AY
Chong
Pele
P
D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000918:Antibody Specificity; D018899:CpG Islands; D004196:Disease Outbreaks; D004655:Emulsions; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology*; D007117:Immunization, Secondary; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000235:genetics*; D015164:Vaccines, Inactivated / Q000737:chemistry / Q000276:immunology
D000276:Adjuvants, Immunologic; D004655:Emulsions; D009838:Oligodeoxyribonucleotides; D015164:Vaccines, Inactivated
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