Nanostructured SBA-15 silica as an adjuvant in immunizations with hepatitis B vaccine

To evaluate the applicability of SBA-15 silica as an adjuvant in immunizations with purified particles of the viral protein HBsAg, the main component of hepatitis B vaccine, Butang^®, produced by Instituto Butantan.

Methods:

BALB/c mice orally or subcutaneously received 0.5 μg of HBsAg adsorbed/encapsulated to SBA-15 or adsorbed to Al(OH)₃. To assess the secondary immune response, a subcutaneous booster was administered 30 days after the first immunization. Individual serum and fecal samples of each group were periodically collected for specific antibody titration by ELISA.

Results:

Analysis of secretory IgA showed that mice orally primed with HBsAg on SBA-15 had increased levels of specific antibodies in primary and secondary immune responses. Specific serum IgA and IgG titers in HBsAg:SBA-15-orally immunized mice reached higher levels after the booster, demonstrating the effectiveness of oral vaccination with the use of silica. All immunized groups showed higher IgG1 levels.

Conclusion:

Our results clearly indicate the promising use of SBA-15 as an adjuvant, especially in oral immunizations.

Keywords:
Hepatitis B; Oral vaccination; Adjuvants; Immunological memory

Authorship

Karina Scaramuzzi

Immunochemistry Laboratory, Instituto Butantan, São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilImmunochemistry Laboratory, Instituto Butantan, São Paulo (SP), Brazil

Denise Cristina André Oliveira

Hepatitis Division, Instituto Butantan – São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilHepatitis Division, Instituto Butantan – São Paulo (SP), Brazil

Luciana Vieira Carvalho

Immunochemistry Laboratory, Instituto Butantan, São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilImmunochemistry Laboratory, Instituto Butantan, São Paulo (SP), Brazil

Denise Vilarinho Tambourgi

Immunochemistry Laboratory, Instituto Butantan, São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilImmunochemistry Laboratory, Instituto Butantan, São Paulo (SP), Brazil

Elisabeth Christina Nunes Tenório

Hepatitis Division, Instituto Butantan – São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilHepatitis Division, Instituto Butantan – São Paulo (SP), Brazil

Marisa Rizzi

Farmacêutica Cristália, São Paulo (SP), BrazilFarmacêutica CristáliaBrazilSão Paulo, SP, BrazilFarmacêutica Cristália, São Paulo (SP), Brazil

Juliana Mussalem

Farmacêutica Cristália, São Paulo (SP), BrazilFarmacêutica CristáliaBrazilSão Paulo, SP, BrazilFarmacêutica Cristália, São Paulo (SP), Brazil

Márcia Carvalho de Abreu Fantini

Department of Applied Physics, Universidade de São Paulo – USP, São Paulo (SP), BrazilUniversidade de São Paulo – USPBrazilSão Paulo, SP, BrazilDepartment of Applied Physics, Universidade de São Paulo – USP, São Paulo (SP), Brazil

Viviane Fongaro Botosso

Hepatitis Division, Instituto Butantan – São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilHepatitis Division, Instituto Butantan – São Paulo (SP), Brazil

Osvaldo Augusto Sant´Anna Corresponding author: Osvaldo Augusto Sant´Anna – Immunochemistry Laboratory, Butantan Institute – São Paulo (SP), Brazil – Tel.: 11 3726-7222 – extension: 2001 – Email: gbrazil@usp.br

Immunochemistry Laboratory, Instituto Butantan, São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilImmunochemistry Laboratory, Instituto Butantan, São Paulo (SP), Brazil

Corresponding author: Osvaldo Augusto Sant´Anna – Immunochemistry Laboratory, Butantan Institute – São Paulo (SP), Brazil – Tel.: 11 3726-7222 – extension: 2001 – Email: gbrazil@usp.br

Conflict of interest: none

SCIMAGO INSTITUTIONS RANKINGS

Immunochemistry Laboratory, Instituto Butantan, São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilImmunochemistry Laboratory, Instituto Butantan, São Paulo (SP), Brazil

Hepatitis Division, Instituto Butantan – São Paulo (SP), BrazilInstituto ButantanBrazilSão Paulo, SP, BrazilHepatitis Division, Instituto Butantan – São Paulo (SP), Brazil

Farmacêutica Cristália, São Paulo (SP), BrazilFarmacêutica CristáliaBrazilSão Paulo, SP, BrazilFarmacêutica Cristália, São Paulo (SP), Brazil

Figures

Figures (5)

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Figure 1
Mesoporous nanostructured SBA-15. (A) Transmission Electron Microscopy (TEM) of SBA-15 silica, highlighting its hexagonal ordered porous structure with mean pore diameter of around 10 nm. (B) Scanning Electron Microscopy (SEM) picture of SBA-15 particles of around 30 μm in diameter, showing their macroporous morphology

Thumbnail

Figure 2
Antibody production by orally or subcutaneously immunized BALB/c mice. (A) Serum IgG, (B) IgG1, (C) IgG2a anti-HBsAg levels (n = 5 animals/group). Antibody titers measured by ELISA 7, 14 and 30 days after booster, administrated subcutaneously 30 days after first immunization. Group of animals immunized with rHBsAg was used as reference for the unpaired Student t test analysis, *p < 0.05; ••• p < 0.001. Antibodies titers at days 7, 14 and 30 after booster were also used as reference for the unpaired Student t test analysis, °p < 0.05

Thumbnail

Figure 3
IgG1 and IgG2a antibody production by subcutaneously immunized BALB/c mice. Serum IgG1 and IgG2a anti-HBsAg antibody levels (n = 5 animals/group). Antibody titers measured by ELISA 7, 14 and 30 days after booster, administrated subcutaneously 30 days after first immunization. IgG1 and IgG2a responses between the groups were used as reference for the unpaired Student t test analysis, *p < 0.05

Thumbnail

Figure 4
IgG1 and IgG2a antibody production by orally immunized BALB/c mice. Serum IgG1 and IgG2a anti-HBsAg antibody levels (n = 5 animals/group). Antibody titers measured by ELISA 7, 14 and 30 days after booster, administrated subcutaneously 30 days after first immunization. IgG1 and IgG2a response between the groups were used as reference for the unpaired Student t test analysis, *** p < 0.05

Thumbnail

Figure 5
Antibody production by orally or subcutaneously immunized BALB/c mice. (A) Secretory IgA (s-IgA) and (B) serum IgA anti-HBsAg levels (n = 5 animals/group). Antibody titers measured by ELISA during primary and secondary immune responses. Subcutaneous booster was administrated 30 days after first oral immunization. Groups of animals non-immunized and immunized with rHBsAg were used as reference for the unpaired Student t test analysis

Figure 1 Mesoporous nanostructured SBA-15. (A) Transmission Electron Microscopy (TEM) of SBA-15 silica, highlighting its hexagonal ordered porous structure with mean pore diameter of around 10 nm. (B) Scanning Electron Microscopy (SEM) picture of SBA-15 particles of around 30 μm in diameter, showing their macroporous morphology

Figure 2 Antibody production by orally or subcutaneously immunized BALB/c mice. (A) Serum IgG, (B) IgG1, (C) IgG2a anti-HBsAg levels (n = 5 animals/group). Antibody titers measured by ELISA 7, 14 and 30 days after booster, administrated subcutaneously 30 days after first immunization. Group of animals immunized with rHBsAg was used as reference for the unpaired Student t test analysis, *p < 0.05; ••• p < 0.001. Antibodies titers at days 7, 14 and 30 after booster were also used as reference for the unpaired Student t test analysis, °p < 0.05

Figure 3 IgG1 and IgG2a antibody production by subcutaneously immunized BALB/c mice. Serum IgG1 and IgG2a anti-HBsAg antibody levels (n = 5 animals/group). Antibody titers measured by ELISA 7, 14 and 30 days after booster, administrated subcutaneously 30 days after first immunization. IgG1 and IgG2a responses between the groups were used as reference for the unpaired Student t test analysis, *p < 0.05

Figure 4 IgG1 and IgG2a antibody production by orally immunized BALB/c mice. Serum IgG1 and IgG2a anti-HBsAg antibody levels (n = 5 animals/group). Antibody titers measured by ELISA 7, 14 and 30 days after booster, administrated subcutaneously 30 days after first immunization. IgG1 and IgG2a response between the groups were used as reference for the unpaired Student t test analysis, *** p < 0.05

Figure 5 Antibody production by orally or subcutaneously immunized BALB/c mice. (A) Secretory IgA (s-IgA) and (B) serum IgA anti-HBsAg levels (n = 5 animals/group). Antibody titers measured by ELISA during primary and secondary immune responses. Subcutaneous booster was administrated 30 days after first oral immunization. Groups of animals non-immunized and immunized with rHBsAg were used as reference for the unpaired Student t test analysis

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Nanostructured SBA-15 silica as an adjuvant in immunizations with hepatitis B vaccine

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[1] Corresponding author: Osvaldo Augusto Sant´Anna – Immunochemistry Laboratory, Butantan Institute – São Paulo (SP), Brazil – Tel.: 11 3726-7222 – extension: 2001 – Email: gbrazil@usp.br