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Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

ABSTRACT: Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal adjuvant for an inactivated split virion H5N1 clade 1 A/Viet Nam1203/2004 (A/VN/1203/04) vaccine in a mouse model. Protollin-adjuvanted vaccines elicited enhanced serum protective hemagglutination inhibition titers, mucosal IgA responses, and H5N1-specific cell-mediated immunity that resulted in complete protection against a lethal challenge with a homologous virus as well as a heterologous clade 2 virus A/Indonesia/05/2005 (A/IN/05/05). Detailed analysis of adaptive immunity revealed that Protollin increased the frequency of lymphoid- as well as local tissue-resident antibody-secreting cells, local germinal center reaction of B cells, broad-spectrum of CD4 T cell response. Our findings suggest that nasal delivery of H5N1 vaccine with Protollin adjuvant can overcome the poor immunogenicity of H5N1 vaccines, induce both cellular and humoral immune responses, enhance protection against challenge with clade 1 and clade 2 H5N1 viruses and achieve significant antigen dose-sparing.

SUBMITTER: Cao W

PROVIDER: S-EPMC7115484 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

Cao Weiping W Kim Jin Hyang JH Reber Adrian J AJ Hoelscher Mary M Belser Jessica A JA Lu Xiuhua X Katz Jacqueline M JM Gangappa Shivaprakash S Plante Martin M Burt David S DS Sambhara Suryaprakash S

Vaccine 20170509 25

Sporadic, yet frequent human infections with avian H5N1 influenza A viruses continue to pose a potential pandemic threat. Poor immunogenicity of unadjuvanted H5N1 vaccines warrants developing novel adjuvants and formulations as well as alternate delivery systems to improve their immunogenicity and efficacy. Here, we show that Protollin, a nasal adjuvant composed of Neisseria meningitides outer membrane proteins non-covalently linked to Shigella flexneri 2a lipopolysaccharide, is a potent nasal a ...[more]

PMID: 28499553

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Project description:Since the first case of human avian influenza A (H7N9) virus infection in 2013, five H7N9 epidemics have occurred in China, all of which caused severe diseases, including pneumonia and acute respiratory distress syndrome, and the fatality rates of these epidemics were as high as 30-40%. To control the prevalence of H7N9 influenza, an effective vaccine is urgently needed. In the present study, we used chitosan and recombinant human interleukin-2 as an adjuvant (JY) to promote the systemic and mucosal immune responses induced by the H7N9 vaccine. Mice were immunized intranasally with the inactivated split influenza A (H7N9) virus (A/Shanghai/02/2013) vaccine with or without JY. The hemagglutination inhibition (HI) titers of mice immunized with the JY-adjuvanted vaccine were significantly higher than those of mice immunized with the vaccine without adjuvant (21.11 ± 9.58 vs. 5.04 ± 3, P < 0.05). The JY-adjuvanted H7N9 nasal spray vaccine induced higher HI titers (8 ± 0.82 vs. 6.7 ± 0.67, P = 0.0035) than those did the poly (I:C)-adjuvanted H7N9 vaccine or the LTB-adjuvanted H7N9 vaccine (8 ± 0.82 vs. 6.9 ± 0.88, P = 0.0186). The optimal immunization regimen for the nasal spray H7N9 vaccine was determined to be a 21-day interval between the primary immunization and booster, with a dose of 4.5 μg hemagglutinin per mouse. The immunogenicities of the nasal spray H7N9 vaccine and intramuscular vaccine (containing only the inactivated split virus) were compared in mice. Two doses of the nasal spray H7N9 vaccine induced higher titers of HI (6.7 ± 0.67 vs. 5.3 ± 1.16, P = 0.004) and anti-HA IgG in sera (19.26 ± 0.67 vs. 13.97 ± 0.82, P < 0.0001) and of anti-HA sIgA (7.13 ± 2.54 vs. 0, P = 0.0000) in bronchoalveolar lavage fluid (BALF) than one dose of intramuscular H7N9 vaccine 3 weeks after the last immunization. However, when we immunized the mice with two doses of both vaccines separately, the nasal spray H7N9 vaccine induced higher titers of anti-HA IgG (19.26 ± 0.67 vs. 17.56 ± 0.57, P < 0.0001) and anti-HA sIgA (7.13 ± 2.54 vs. 4.02 ± 0.33, P = 0.0026) than did the intramuscular H7N9 vaccine, and there was no difference in HI titer between the two groups (P = 0.3745). This finding indicates that the JY-adjuvanted nasal spray H7N9 vaccine induced not only the systemic immune response but also a local mucosal response, which may improve the efficacy of H7N9 influenza prevention through respiratory tract transmission.

Dataset Information

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

Publications

Nasal delivery of Protollin-adjuvanted H5N1 vaccine induces enhanced systemic as well as mucosal immunity in mice.

Similar Datasets

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