Abstract
BackgroundAntigen 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.Methodology/Principal FindingsAfter formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span®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 µg 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/SignificanceEncapsulating 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.
Highlights
Vaccination is the best cost-effective biomedical approach in the face of the threat of the emerging diseases like influenza epidemics and pandemics [1,2]
In preparation for a potential shortage of pandemic influenza vaccine, we have previously developed the production process for the World Health Organization (WHO) vaccine strain NIBRG-14 using Madin-Darby canine kidney (MDCK) cells, growing either in roller-bottles
We found that when the same amount of inactivated virus was co-administered with either alum or PELC, the induced anti-NIBRG-14 neutralizing titers were significantly higher than those induced by non-adjuvanted inactivated virus. 5 mg HA of PELC-formulated inactivated virus was capable of inducing higher antibodies than those obtained from alum-adjuvanted virus
Summary
Vaccination is the best cost-effective biomedical approach in the face of the threat of the emerging diseases like influenza epidemics and pandemics [1,2]. In preparedness of influenza pandemic vaccine, two of the key challenges are to produce sufficient quantities of vaccine in a narrowed time window and to induce significant immunogenicity and cross-protective immunity after vaccine injections [1,2,3]. Both targets can be achieved by using an additive substance dubbed adjuvant to elicit a robust and broadened immune response [3]. 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
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