Chitosan Nanoparticle as a Novel Delivery System for A/H1n1 Influenza Vaccine: Safe Property and Immunogenicity in Mice
The aims of this paper are to study the efficacy of
chitosan nanoparticles in stimulating specific antibody against
A/H1N1 influenza antigen in mice. Chitosan nanoparticles (CSN)
were characterized by TEM. The results showed that the average size
of CSN was from 80nm to 106nm. The efficacy of A/H1N1 influenza
vaccine loaded on the surface of CSN showed that loading efficiency
of A/H1N1 influenza antigen on CSN was from 93.75 to 100%. Safe
property of the vaccine were tested. In 10 days post vaccination,
group of CSN 30 kDa and 300 kDa loaded A/H1N1 influenza antigen
were the rate of immune response on mice to be 100% (9/9) higher
than Al(OH)3 and other adjuvant. 100% mice in the experiment of all
groups had immune response in 20 days post vaccination. The results
also showed that HI titer of the group using CSN 300 kDa as an
adjuvant increased significantly up to 3971 HIU, over three-fold
higher than the Al(OH)3 adjuvant, chitosan (CS), and one hundredfold
than the A/H1N1 antigen only. Stability of the vaccine
formulation was investigated.
[1] WHO. WHO Media Influenza Factsheet N0211. 2003;
http:/www.who.int/mediacentre/factsheets/2003/fs211/en/.
[2] WHO. 6th WHO Meeting on Evaluation of Pandemic Influenza Vaccines
in Clinical Trials, February, 2010.
[3] B. P. Arulanandam, M. O- Toole, D. W. Metzger. Intranasal interleukin-
12 is a powerful adjuvant for protective mucosal immunity. Journal
Infection Disease; 180: 940-949, 1999.
[4] B. Guy, N. Pascal, A. Francon. Design, characterization and preclinicl
efficacy of a cationic lipid adjuvant for influenza split vaccine. Vaccine,
Vol. 19: 1794-1805, 2001.
[5] I. Bracci, I. Caniti & S. Puzelli. Type I IFN as a vaccine adjuvant for
both systemic and mucosal vaccination against influenza virus. Vaccine;
24 (suppl.2):2: 56-57, 2006.
[6] S. K. Song, Z. Moldoveanu & H. H. Nguyen. Intranasal immunization
with influenza virus and Korean misteloe lectin C (KML-C) induces
heterosubtypic immunity in mice. Vaccine; 25: 6359-6366. 2007.
[7] S. Y. Ko, H. J. Ko, W. S. Chang, S.H. Park, M. N. Kweon & C. Y.
Kang. Alpha-Galactosylceramide can act as a nasal vaccine adjuvant
inducing protective immune responses against viral infection and tumor.
J. Immunol; 175: 3309-3317. 2005.
[8] H. J. Youn, S. Y. Ko & K. A. Lee. A single intranasal immunization
with inactivated influenza virus and alpha-Galactosylceramide induces
long-term protective immunity without redirecting antigen to the
respiratory pathogens. Vaccine; 25: 5189-5198, 2007.
[9] I. Illium, J. Gill, M. Hinchcliffe, A. N. Fisher & S. S. Davis. Chitosan as
a novel nasal delivery system for vaccines. Advanced drug delivery
review; 51: 81-96, 2001.
[10] J. Huang, R. J. Garmise & T. M. Crowder. A novel dry powder
influenza vaccine intranasal delivery technology: induction of systemic
and mucosal immune response in rats. Vaccine; 23: 144-153. 2004.
[11] M. Amidi, S. G. Romeijn, J. C. Verhoef, H. E. Junginger, L. Bungener,
A. Huckriede, D. J. A. Crommelin & W. Jiskoot. N- Trimethyl chitosan
(TMC) nanoparticles loaded subunit antigen for intranasal vaccination:
Biological properties and immunogenicity in a mouse model. Vaccine;
25: 144-153, 2007.
[12] R.J. Garmise, H. F. Staats & A. J. Hickey. A novel dry powder
preparation of whole inactivated influenza virus for nasal vaccination. e.
Design, characterization and preclinical efficacy of a cationic lipid
adjuvant for influenza split vaccine. Vaccine; 19: 1794-1805, 2007.
[13] R. M. N. V. Kumar. A review of chitin and chitosan applications.
Reactive & Funtion Polymer; 46, 1-27, 2000.
[14] M. Rinaudo. Chitin and chitosan: properties and application, Progress in
polymer science; 31, 603-632, 2006.
[15] H. K. No, N. J . Park, S. H. Lee, S. P. Meyers. Antibacterial activity of
chitosans and chitosan oligomers with different molecular weights.
International Journal of Food Microbiology; 74, 65 - 72, 2002.
[16] P. Sanpui, A. Murugadoss, P. V. Durga Prasad, S. S. Gosh, A.
Chattopadhyay. The antibacterial properties of a novel chitosan-Agnanoparticle.
International Journal of Food Microbiology; 124, 142-
146, 2008.
[17] L. Qi, Z. Xu, X. Jiang, C. Hu & X. Zou. Preparation and antibacterial
activity of chitosan nanoparticles. Carbohydrate Research; 339, 2693-
2700, 2004.
[18] M. R. Avadi, A.M.M. Sadeghi, A. Tahzibi, K. Bayati, M. Pouladzadeh,
M. Zohuriaan, M. Rafiee-Tehrani. Diethylmethyl chitosan as an
antimicrobial agent: Synthesis, characterization and antibacterial effects.
European Polymer Journal; 40: 1355-1361, 2004.
[19] K. Xing, X. G. Chen, Y.Y. Li, C.S. Liu, C.G. Liu, D.S. Cha, H.J. Park.
Antibacterial activity of oleoyl-chitosan nanoparticles: A novel
antibacterial dispersion system. Carbohydrate Polymer; 74: 114-120,
2008.
[20] F. C. MacLaughlin, R. J. Mumper, J. Wang, J. M. Tagliaferri, I. Gill, M.
Hinchcliffe, A.P. Rolland. Chitosan and depolymerized chitosan
oligomers as condensing carriers for in vivo plasmid delivery. Journal of
Controlled Release; 56: 259-272, 1998.
[21] T. Kean, S. Roth & M. Thanou. Trimethylated chitosans as non-viral
gene delivery vectors: Cytotoxicity and transfection efficiency. Journal
of Controlled Release; 2005; 103: 643-653.
[22] T. Kiang, J. Wen, H.W. Lim & K.W. Leong. The effect of the degree of
chitosan deacetylation on the efficiency of gene transfection.
Biomaterials; 25: 5293-5301, 2005.
[23] Q. Gan, T. Wang, C. Cochrane & P. McCarron. Modulation of surface
charge, particle size and morphological properties of chitosan-TPP
nanoparticles intended for gene delivery. Colloids and Surfaces B:
Biointerfaces; 44: 65-73, 2005.
[24] A. M. De Campos, A. Sanchez, M. J. Alonso. Chitosan nanoparticles: a
new vehicle for the improvement of the delivery of drugs to the ocular
surface. Application to cyclosporine A. International Journal of
Pharmaceutics; 224: 159-168, 2001.
[25] M. H. El-Salbouri. Positively charged nanoparticles for improving the
oral bioavailability of cyclosporine A. International Journal of
Pharmaceutics; 249: 101-108, 2001.
[26] J. Zhang, X. G. Chen, Y. Y. Li & C. S. Liu. Self-assembled
nanoparticles based on hydrophobically modified chitosan as carriers for
doxorubicin. Nanomedicine: Nanotechnology, Biology, and Medicine; 3:
258-265, 2007.
[27] Q. Gan & T. Wang. Chitosan nanoparticles as protein delivery carrierssystematic
examination of fabrication conditions for efficient loading
and release. Colloids and Surfaces B: Biointerfaces; 59: 24-34, 2007.
[28] B. Sarmento, A. Ribeiro, F. Veiga & D. Ferreira. Development and
characterization of new insulin containing polysaccharide nanoparticles.
Colloids and Surfaces B: Biointerfaces; 53: 193-202, 2006.
[29] Y. Zheng. Nanoparticles based on the complex of chitosan with
polyaspartic acid sodium salt: preparation, characterization and the use
for 5-fluorouracil delivery, European Journal of Pharmaceutic and
Biopharmaceutics; 67: 621-631, 2007.
[30] P. G. Seferia & M. L. Martinez. Immune stimulating activity of two new
chitosan containing adjuvant formulation. Vaccine; 19: 661-668, 2001.
[31] O. Borges, J. Tavares, A. de Sousa, G. Borchard, H. E. Junginger & A.
Cordeiro-da-Silva. Evaluation of the immune response following a short
oral vaccination schedule with hepatitis B antigen encapsulated into
alginate-coated chitosan nanoparticles. European Journal of
Pharmaceutical Science; 32: 278-290, 2007.
[32] D. A. Zaharoff, J. R. Connie, W. H. Kenneth, S. Jeffrey, W. G. John.
Chitosan solution enhances the immunoadjuvant properties of GM-CSF.
Vaccine; 25: 8673-8686, 2007.
[33] I. M. vander Lubben, J. C. Verhoef, G. Borchard, H. E. Junginger.
Chitosan and its derivatives in mucosal drug and vaccine delivery.
European Journal of Pharmaceutical Science; 14: 201-207, 2001.
[34] A. Vila, A. Sanchez, K. Jane, I. Behrens, T. Kissel, J. L. V. Jato & M. J.
Alonso. Low molecular weight chitosan nanoparticles as a new carrier
for nasal vaccine delivery in mice. European Journal of Pharmaceutics
and Biopharmaceutics; 2004; 57: 123-131.
[35] K. Khatri, A. K. Goyal, P. N. Gupta, N. Mishra & S. P. Vyas. Plasmid
DNA loaded chitosan nanoparticles for nasal mucosal immunization
against hepatitis B. International Journal of Pharmaceutics; 354: 235-
241, 2008.
[36] O. Borges, G. Borchard, A. de Sousa, H. E. Junginger & A. Cordeiro-da-
Silva. Induction of lymphocytes activated maker CD69 following
exposure to chitosan and alginate biopolymers. International Journal of
Pharmaceutics; 337: 254-264, 2008.
[37] O. Borges, A. Cordeiro-da-Silva, J. Tavares, N. Santarem, A. Sousa, G.
Borchard & H.E. Junginger. Immune response by nasal delivery of
hepatitis B surface antigen and codelivery of a CpG ODN in alginate
coated chitosan nanoparticles. European Journal of Pharmaceutical and
Biopharmaceutics; 69: 405-416, 2008.
[38] Y. Yang, J. Chen, H. Li, Y. Wang, Z. Xie, M. Wu, H. Zang, Z. Zhao.
Porcine interleukin-2 gene encapsulated in chitosan nanoparticles
enhances immune response of mice to piglet paratyphoid vaccine.
Comparative Immunology, Microbiology & Infectious Diseases; 30: 19-
32, 2007.
[39] N. Hagennars, R. J. Verheul, I. Mooren, P. H. de Jong. Relationship
between structure and adjuvanticity of N, N, N - Trimethyl chitosan
(TMC) structural variants in a nasal influenza vaccine. Journal of
controlled Release; 140:126-133, 2009.
[40] D. Coucke, M. Schotsaert, C. Libert, E. Pringels, C. Vervaet, P.
Foreman, X. Saelens & J. P. Remon. Spray-dried powders of starch and
crosslinked poly (acrylic acid) as carriers for nasal delivery of
inactivated influenza vaccine. Vaccine; 27: 1279-1286, 2009.
[41] S. Shan, E. Poinern, T. Ellis, S. Fanwick, X. Le, J. Edward & J.T. Jiang.
Development of a Nano vaccine against wild bird H6N2 avian influenza
virus. Procedia in Vaccinology; 2: 40-43, 2010.
[42] L.V. Hiep, M.T. Thanh, D. T. H. Van, V. T. P. Khanh & N. A. Dzung.
Chitosan as a hopeful adjuvant for H5N1 influenza vaccine. Journal
Chitin and Chitosan; 13(10): 6-8, 2008.
[43] [43] WHO. Egg-based influenza vaccine manufacturing course manual,
2009, Part II. Netherlands Vaccine Institute, Bilthoven, The Netherlands.
[44] M. L. Killian. Haemaglutinine assay for Avian influenza Virus, In
Methods in Molecular Biology, Vol. 436: Avian Influenza Virus 2008;
47-56. Edited by Erica Spackman, Humana Press, Totowa, NY.
[45] M. Huang, C. W. Fong, E. Khor & Y. Y. Lim. Transfection efficiency of
chitosan vectors: effect of polymer molecular weight and degree of
deacetylation. Journal of Controlled Release; 106: 391-406, 2005.
[46] VTTC. Quality Control of DPT Vaccines, chapter 6: Toxicity testing,
RIVM, Netherland, 2000; 224-230.
[47] V. Kunzi, J. M. Klap, M. K. Seiberling, C. Herzog, K. Hartmann, O.
Kusteiner, R. Kompier, R. Grimaldi, J. Goudsmit. Immunogenicity and
safety of low dose virosomal adjuvant influenza vaccine administered
intradermally compared to intramuscular full dose administration.
Vaccine; 27: 3561-3567, 2009.
[48] M. Nishino, D. Mizuno, T. Kimoto, W. Shinahara, A. Fukuta, T. Takei,
K. Sumida, S. Kitamura, H. Shiota, H. Kido. Influenza vaccine with
Surfacten: a modified pulmonary surfactant, induce systemic and
mucosal immune responses without side effect in minipig. Vaccine; 27:
5620-5627, 2009.
[1] WHO. WHO Media Influenza Factsheet N0211. 2003;
http:/www.who.int/mediacentre/factsheets/2003/fs211/en/.
[2] WHO. 6th WHO Meeting on Evaluation of Pandemic Influenza Vaccines
in Clinical Trials, February, 2010.
[3] B. P. Arulanandam, M. O- Toole, D. W. Metzger. Intranasal interleukin-
12 is a powerful adjuvant for protective mucosal immunity. Journal
Infection Disease; 180: 940-949, 1999.
[4] B. Guy, N. Pascal, A. Francon. Design, characterization and preclinicl
efficacy of a cationic lipid adjuvant for influenza split vaccine. Vaccine,
Vol. 19: 1794-1805, 2001.
[5] I. Bracci, I. Caniti & S. Puzelli. Type I IFN as a vaccine adjuvant for
both systemic and mucosal vaccination against influenza virus. Vaccine;
24 (suppl.2):2: 56-57, 2006.
[6] S. K. Song, Z. Moldoveanu & H. H. Nguyen. Intranasal immunization
with influenza virus and Korean misteloe lectin C (KML-C) induces
heterosubtypic immunity in mice. Vaccine; 25: 6359-6366. 2007.
[7] S. Y. Ko, H. J. Ko, W. S. Chang, S.H. Park, M. N. Kweon & C. Y.
Kang. Alpha-Galactosylceramide can act as a nasal vaccine adjuvant
inducing protective immune responses against viral infection and tumor.
J. Immunol; 175: 3309-3317. 2005.
[8] H. J. Youn, S. Y. Ko & K. A. Lee. A single intranasal immunization
with inactivated influenza virus and alpha-Galactosylceramide induces
long-term protective immunity without redirecting antigen to the
respiratory pathogens. Vaccine; 25: 5189-5198, 2007.
[9] I. Illium, J. Gill, M. Hinchcliffe, A. N. Fisher & S. S. Davis. Chitosan as
a novel nasal delivery system for vaccines. Advanced drug delivery
review; 51: 81-96, 2001.
[10] J. Huang, R. J. Garmise & T. M. Crowder. A novel dry powder
influenza vaccine intranasal delivery technology: induction of systemic
and mucosal immune response in rats. Vaccine; 23: 144-153. 2004.
[11] M. Amidi, S. G. Romeijn, J. C. Verhoef, H. E. Junginger, L. Bungener,
A. Huckriede, D. J. A. Crommelin & W. Jiskoot. N- Trimethyl chitosan
(TMC) nanoparticles loaded subunit antigen for intranasal vaccination:
Biological properties and immunogenicity in a mouse model. Vaccine;
25: 144-153, 2007.
[12] R.J. Garmise, H. F. Staats & A. J. Hickey. A novel dry powder
preparation of whole inactivated influenza virus for nasal vaccination. e.
Design, characterization and preclinical efficacy of a cationic lipid
adjuvant for influenza split vaccine. Vaccine; 19: 1794-1805, 2007.
[13] R. M. N. V. Kumar. A review of chitin and chitosan applications.
Reactive & Funtion Polymer; 46, 1-27, 2000.
[14] M. Rinaudo. Chitin and chitosan: properties and application, Progress in
polymer science; 31, 603-632, 2006.
[15] H. K. No, N. J . Park, S. H. Lee, S. P. Meyers. Antibacterial activity of
chitosans and chitosan oligomers with different molecular weights.
International Journal of Food Microbiology; 74, 65 - 72, 2002.
[16] P. Sanpui, A. Murugadoss, P. V. Durga Prasad, S. S. Gosh, A.
Chattopadhyay. The antibacterial properties of a novel chitosan-Agnanoparticle.
International Journal of Food Microbiology; 124, 142-
146, 2008.
[17] L. Qi, Z. Xu, X. Jiang, C. Hu & X. Zou. Preparation and antibacterial
activity of chitosan nanoparticles. Carbohydrate Research; 339, 2693-
2700, 2004.
[18] M. R. Avadi, A.M.M. Sadeghi, A. Tahzibi, K. Bayati, M. Pouladzadeh,
M. Zohuriaan, M. Rafiee-Tehrani. Diethylmethyl chitosan as an
antimicrobial agent: Synthesis, characterization and antibacterial effects.
European Polymer Journal; 40: 1355-1361, 2004.
[19] K. Xing, X. G. Chen, Y.Y. Li, C.S. Liu, C.G. Liu, D.S. Cha, H.J. Park.
Antibacterial activity of oleoyl-chitosan nanoparticles: A novel
antibacterial dispersion system. Carbohydrate Polymer; 74: 114-120,
2008.
[20] F. C. MacLaughlin, R. J. Mumper, J. Wang, J. M. Tagliaferri, I. Gill, M.
Hinchcliffe, A.P. Rolland. Chitosan and depolymerized chitosan
oligomers as condensing carriers for in vivo plasmid delivery. Journal of
Controlled Release; 56: 259-272, 1998.
[21] T. Kean, S. Roth & M. Thanou. Trimethylated chitosans as non-viral
gene delivery vectors: Cytotoxicity and transfection efficiency. Journal
of Controlled Release; 2005; 103: 643-653.
[22] T. Kiang, J. Wen, H.W. Lim & K.W. Leong. The effect of the degree of
chitosan deacetylation on the efficiency of gene transfection.
Biomaterials; 25: 5293-5301, 2005.
[23] Q. Gan, T. Wang, C. Cochrane & P. McCarron. Modulation of surface
charge, particle size and morphological properties of chitosan-TPP
nanoparticles intended for gene delivery. Colloids and Surfaces B:
Biointerfaces; 44: 65-73, 2005.
[24] A. M. De Campos, A. Sanchez, M. J. Alonso. Chitosan nanoparticles: a
new vehicle for the improvement of the delivery of drugs to the ocular
surface. Application to cyclosporine A. International Journal of
Pharmaceutics; 224: 159-168, 2001.
[25] M. H. El-Salbouri. Positively charged nanoparticles for improving the
oral bioavailability of cyclosporine A. International Journal of
Pharmaceutics; 249: 101-108, 2001.
[26] J. Zhang, X. G. Chen, Y. Y. Li & C. S. Liu. Self-assembled
nanoparticles based on hydrophobically modified chitosan as carriers for
doxorubicin. Nanomedicine: Nanotechnology, Biology, and Medicine; 3:
258-265, 2007.
[27] Q. Gan & T. Wang. Chitosan nanoparticles as protein delivery carrierssystematic
examination of fabrication conditions for efficient loading
and release. Colloids and Surfaces B: Biointerfaces; 59: 24-34, 2007.
[28] B. Sarmento, A. Ribeiro, F. Veiga & D. Ferreira. Development and
characterization of new insulin containing polysaccharide nanoparticles.
Colloids and Surfaces B: Biointerfaces; 53: 193-202, 2006.
[29] Y. Zheng. Nanoparticles based on the complex of chitosan with
polyaspartic acid sodium salt: preparation, characterization and the use
for 5-fluorouracil delivery, European Journal of Pharmaceutic and
Biopharmaceutics; 67: 621-631, 2007.
[30] P. G. Seferia & M. L. Martinez. Immune stimulating activity of two new
chitosan containing adjuvant formulation. Vaccine; 19: 661-668, 2001.
[31] O. Borges, J. Tavares, A. de Sousa, G. Borchard, H. E. Junginger & A.
Cordeiro-da-Silva. Evaluation of the immune response following a short
oral vaccination schedule with hepatitis B antigen encapsulated into
alginate-coated chitosan nanoparticles. European Journal of
Pharmaceutical Science; 32: 278-290, 2007.
[32] D. A. Zaharoff, J. R. Connie, W. H. Kenneth, S. Jeffrey, W. G. John.
Chitosan solution enhances the immunoadjuvant properties of GM-CSF.
Vaccine; 25: 8673-8686, 2007.
[33] I. M. vander Lubben, J. C. Verhoef, G. Borchard, H. E. Junginger.
Chitosan and its derivatives in mucosal drug and vaccine delivery.
European Journal of Pharmaceutical Science; 14: 201-207, 2001.
[34] A. Vila, A. Sanchez, K. Jane, I. Behrens, T. Kissel, J. L. V. Jato & M. J.
Alonso. Low molecular weight chitosan nanoparticles as a new carrier
for nasal vaccine delivery in mice. European Journal of Pharmaceutics
and Biopharmaceutics; 2004; 57: 123-131.
[35] K. Khatri, A. K. Goyal, P. N. Gupta, N. Mishra & S. P. Vyas. Plasmid
DNA loaded chitosan nanoparticles for nasal mucosal immunization
against hepatitis B. International Journal of Pharmaceutics; 354: 235-
241, 2008.
[36] O. Borges, G. Borchard, A. de Sousa, H. E. Junginger & A. Cordeiro-da-
Silva. Induction of lymphocytes activated maker CD69 following
exposure to chitosan and alginate biopolymers. International Journal of
Pharmaceutics; 337: 254-264, 2008.
[37] O. Borges, A. Cordeiro-da-Silva, J. Tavares, N. Santarem, A. Sousa, G.
Borchard & H.E. Junginger. Immune response by nasal delivery of
hepatitis B surface antigen and codelivery of a CpG ODN in alginate
coated chitosan nanoparticles. European Journal of Pharmaceutical and
Biopharmaceutics; 69: 405-416, 2008.
[38] Y. Yang, J. Chen, H. Li, Y. Wang, Z. Xie, M. Wu, H. Zang, Z. Zhao.
Porcine interleukin-2 gene encapsulated in chitosan nanoparticles
enhances immune response of mice to piglet paratyphoid vaccine.
Comparative Immunology, Microbiology & Infectious Diseases; 30: 19-
32, 2007.
[39] N. Hagennars, R. J. Verheul, I. Mooren, P. H. de Jong. Relationship
between structure and adjuvanticity of N, N, N - Trimethyl chitosan
(TMC) structural variants in a nasal influenza vaccine. Journal of
controlled Release; 140:126-133, 2009.
[40] D. Coucke, M. Schotsaert, C. Libert, E. Pringels, C. Vervaet, P.
Foreman, X. Saelens & J. P. Remon. Spray-dried powders of starch and
crosslinked poly (acrylic acid) as carriers for nasal delivery of
inactivated influenza vaccine. Vaccine; 27: 1279-1286, 2009.
[41] S. Shan, E. Poinern, T. Ellis, S. Fanwick, X. Le, J. Edward & J.T. Jiang.
Development of a Nano vaccine against wild bird H6N2 avian influenza
virus. Procedia in Vaccinology; 2: 40-43, 2010.
[42] L.V. Hiep, M.T. Thanh, D. T. H. Van, V. T. P. Khanh & N. A. Dzung.
Chitosan as a hopeful adjuvant for H5N1 influenza vaccine. Journal
Chitin and Chitosan; 13(10): 6-8, 2008.
[43] [43] WHO. Egg-based influenza vaccine manufacturing course manual,
2009, Part II. Netherlands Vaccine Institute, Bilthoven, The Netherlands.
[44] M. L. Killian. Haemaglutinine assay for Avian influenza Virus, In
Methods in Molecular Biology, Vol. 436: Avian Influenza Virus 2008;
47-56. Edited by Erica Spackman, Humana Press, Totowa, NY.
[45] M. Huang, C. W. Fong, E. Khor & Y. Y. Lim. Transfection efficiency of
chitosan vectors: effect of polymer molecular weight and degree of
deacetylation. Journal of Controlled Release; 106: 391-406, 2005.
[46] VTTC. Quality Control of DPT Vaccines, chapter 6: Toxicity testing,
RIVM, Netherland, 2000; 224-230.
[47] V. Kunzi, J. M. Klap, M. K. Seiberling, C. Herzog, K. Hartmann, O.
Kusteiner, R. Kompier, R. Grimaldi, J. Goudsmit. Immunogenicity and
safety of low dose virosomal adjuvant influenza vaccine administered
intradermally compared to intramuscular full dose administration.
Vaccine; 27: 3561-3567, 2009.
[48] M. Nishino, D. Mizuno, T. Kimoto, W. Shinahara, A. Fukuta, T. Takei,
K. Sumida, S. Kitamura, H. Shiota, H. Kido. Influenza vaccine with
Surfacten: a modified pulmonary surfactant, induce systemic and
mucosal immune responses without side effect in minipig. Vaccine; 27:
5620-5627, 2009.
@article{"International Journal of Biological, Life and Agricultural Sciences:54192", author = "Nguyen Anh Dzung and Nguyen Thi Ngoc Hà and Dang Thi Hong Van and Nguyen Thi Lan Phuong and Nguyen Thi
Nhu Quynh and Dinh Minh Hiep and Le Van Hiep", title = "Chitosan Nanoparticle as a Novel Delivery System for A/H1n1 Influenza Vaccine: Safe Property and Immunogenicity in Mice", abstract = "The aims of this paper are to study the efficacy of
chitosan nanoparticles in stimulating specific antibody against
A/H1N1 influenza antigen in mice. Chitosan nanoparticles (CSN)
were characterized by TEM. The results showed that the average size
of CSN was from 80nm to 106nm. The efficacy of A/H1N1 influenza
vaccine loaded on the surface of CSN showed that loading efficiency
of A/H1N1 influenza antigen on CSN was from 93.75 to 100%. Safe
property of the vaccine were tested. In 10 days post vaccination,
group of CSN 30 kDa and 300 kDa loaded A/H1N1 influenza antigen
were the rate of immune response on mice to be 100% (9/9) higher
than Al(OH)3 and other adjuvant. 100% mice in the experiment of all
groups had immune response in 20 days post vaccination. The results
also showed that HI titer of the group using CSN 300 kDa as an
adjuvant increased significantly up to 3971 HIU, over three-fold
higher than the Al(OH)3 adjuvant, chitosan (CS), and one hundredfold
than the A/H1N1 antigen only. Stability of the vaccine
formulation was investigated.", keywords = "Chitosan nanoparticles, A/H1N1 influenza antigen,
vaccine, immunogenicity, adjuvant, antibody titer", volume = "5", number = "12", pages = "902-8", }
