tetano
Editor, Senior Moderator
Aalzen de Haana,
Bert Jan Haijemab, Corresponding author contact information, E-mail the corresponding author,
Petra Voornb,
Tjarko Meijerhofa,
Maarten L. van Roosmalenb,
Kees Leenhoutsb
a Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
b Mucosis BV, Groningen, The Netherlands
Received 1 February 2012. Revised 5 April 2012. Accepted 9 April 2012. Available online 23 April 2012.
http://dx.doi.org/10.1016/j.vaccine.2012.04.032, How to Cite or Link Using DOI
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.
Highlights
► Supplementation of IN administered vaccine with BLP increases serum IgG. ► Supplementation of IN administered vaccine with BLP induces sIgA. ► In BLP-adjuvanted vaccine provides protection against live virus infection. ► In BLP-adjuvanted vaccine reduces lung viral titers compared to IM vaccination.
http://www.sciencedirect.com/science/article/pii/S0264410X12005634
Bert Jan Haijemab, Corresponding author contact information, E-mail the corresponding author,
Petra Voornb,
Tjarko Meijerhofa,
Maarten L. van Roosmalenb,
Kees Leenhoutsb
a Department of Medical Microbiology, Molecular Virology Section, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands
b Mucosis BV, Groningen, The Netherlands
Received 1 February 2012. Revised 5 April 2012. Accepted 9 April 2012. Available online 23 April 2012.
http://dx.doi.org/10.1016/j.vaccine.2012.04.032, How to Cite or Link Using DOI
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.
Highlights
► Supplementation of IN administered vaccine with BLP increases serum IgG. ► Supplementation of IN administered vaccine with BLP induces sIgA. ► In BLP-adjuvanted vaccine provides protection against live virus infection. ► In BLP-adjuvanted vaccine reduces lung viral titers compared to IM vaccination.
http://www.sciencedirect.com/science/article/pii/S0264410X12005634