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Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration.
Vaccine. 2012 Jul 06; 30(32):4884-91.V

Abstract

Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local protective antibodies, i.e. S-IgA. Most commercially available vaccines however are inactivated non-replicating vaccines and have a low immunogenicity when administered intranasally. Local administration of these vaccines would therefore need an adjuvant to boost systemic and local antibody responses. Here we explored the use of a safe adjuvant system, i.e. bacterium-like particles (BLPs) derived from the food-grade bacterium in Lactococcus lactis, in the induction of protective antibody responses after intranasal immunization of mice. Supplementation of H1N1 split vaccine with BLPs significantly increased levels of serum influenza-specific IgG and hemagglutination-inhibiting antibodies: this was dependent on the dose of admixed BLPs and number of immunizations. Admixing BLPs further boosted local influenza-specific S-IgA antibody levels at lung and nasal mucosal sites, but also at distant mucosal sites such as the vaginal mucosal tissue. Mice immunized IN with BLP-adjuvanted vaccine and IM with non-adjuvanted vaccine were protected against weight loss upon homologous infection with H1N1 A/PR/8/34. Full protection against weight loss upon heterologous challenge with H1N1 A/PR/8/34 was seen in mice immunized IN with BLP-adjuvanted H1N1 A/New Caledonia-derived split virus vaccine, but not in those receiving the split virus vaccine IM. Mice immunized IN with BLP-adjuvanted vaccine had significantly lower lung viral titers upon homologous and heterologous challenge when compared to titers detected in mice immunized by IM injection of non-adjuvanted vaccine. Thus, adjuvantation of IN-administered influenza vaccines with BLPs effectively enhances systemic and local antibody responses leading to a superior protection against homologous and heterologous influenza infection compared to conventional IM immunization.

Authors+Show Affiliations

Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22537989

Citation

de Haan, Aalzen, et al. "Bacterium-like Particles Supplemented With Inactivated Influenza Antigen Induce Cross-protective Influenza-specific Antibody Responses Through Intranasal Administration." Vaccine, vol. 30, no. 32, 2012, pp. 4884-91.
de Haan A, Haijema BJ, Voorn P, et al. Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration. Vaccine. 2012;30(32):4884-91.
de Haan, A., Haijema, B. J., Voorn, P., Meijerhof, T., van Roosmalen, M. L., & Leenhouts, K. (2012). Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration. Vaccine, 30(32), 4884-91. https://doi.org/10.1016/j.vaccine.2012.04.032
de Haan A, et al. Bacterium-like Particles Supplemented With Inactivated Influenza Antigen Induce Cross-protective Influenza-specific Antibody Responses Through Intranasal Administration. Vaccine. 2012 Jul 6;30(32):4884-91. PubMed PMID: 22537989.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration. AU - de Haan,Aalzen, AU - Haijema,Bert Jan, AU - Voorn,Petra, AU - Meijerhof,Tjarko, AU - van Roosmalen,Maarten L, AU - Leenhouts,Kees, Y1 - 2012/04/23/ PY - 2012/02/01/received PY - 2012/04/05/revised PY - 2012/04/09/accepted PY - 2012/4/28/entrez PY - 2012/4/28/pubmed PY - 2012/10/26/medline SP - 4884 EP - 91 JF - Vaccine JO - Vaccine VL - 30 IS - 32 N2 - Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local protective antibodies, i.e. S-IgA. Most commercially available vaccines however are inactivated non-replicating vaccines and have a low immunogenicity when administered intranasally. Local administration of these vaccines would therefore need an adjuvant to boost systemic and local antibody responses. Here we explored the use of a safe adjuvant system, i.e. bacterium-like particles (BLPs) derived from the food-grade bacterium in Lactococcus lactis, in the induction of protective antibody responses after intranasal immunization of mice. Supplementation of H1N1 split vaccine with BLPs significantly increased levels of serum influenza-specific IgG and hemagglutination-inhibiting antibodies: this was dependent on the dose of admixed BLPs and number of immunizations. Admixing BLPs further boosted local influenza-specific S-IgA antibody levels at lung and nasal mucosal sites, but also at distant mucosal sites such as the vaginal mucosal tissue. Mice immunized IN with BLP-adjuvanted vaccine and IM with non-adjuvanted vaccine were protected against weight loss upon homologous infection with H1N1 A/PR/8/34. Full protection against weight loss upon heterologous challenge with H1N1 A/PR/8/34 was seen in mice immunized IN with BLP-adjuvanted H1N1 A/New Caledonia-derived split virus vaccine, but not in those receiving the split virus vaccine IM. Mice immunized IN with BLP-adjuvanted vaccine had significantly lower lung viral titers upon homologous and heterologous challenge when compared to titers detected in mice immunized by IM injection of non-adjuvanted vaccine. Thus, adjuvantation of IN-administered influenza vaccines with BLPs effectively enhances systemic and local antibody responses leading to a superior protection against homologous and heterologous influenza infection compared to conventional IM immunization. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/22537989/Bacterium_like_particles_supplemented_with_inactivated_influenza_antigen_induce_cross_protective_influenza_specific_antibody_responses_through_intranasal_administration_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(12)00563-4 DB - PRIME DP - Unbound Medicine ER -