Hepatitis B vaccine induces apoptotic death in Hepa1-6 cells

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" We conclude that exposure of Hepa1-6 cells to a low dose of adjuvanted

hepatitis B vaccine leads to loss of mitochondrial integrity, apoptosis

induction, and cell death, apoptosis effect was observed also in C2C12

mouse myoblast cell line after treated with low dose of vaccine (0.3,

0.1, 0.05 ?g/ml). In addition In vivo apoptotic effect of hepatitis B

vaccine was observed in mouse liver. " (1)

" Findings suggest that U.S. male neonates vaccinated with the hepatitis

B vaccine prior to 1999 (from vaccination record) had a threefold higher

risk for parental report of autism diagnosis compared to boys not

vaccinated as neonates during that same time period. Nonwhite boys bore

a greater risk. " (2)

1. Hepatitis B vaccine induces apoptotic death in Hepa1-6 cells.

<http://www.ncbi.nlm.nih.gov/pubmed/22249285>

Hamza H, Cao J, Li X, Li C, Zhu M, Zhao S.

Apoptosis. 2012 Jan 17. [Epub ahead of print]

Vaccines can have adverse side-effects, and these are predominantly

associated with the inclusion of chemical additives such as aluminum

hydroxide adjuvant. The objective of this study was to establish an in

vitro model system amenable to mechanistic investigations of

cytotoxicity induced by hepatitis B vaccine, and to investigate the

mechanisms of vaccine-induced cell death. The mouse liver hepatoma cell

line Hepa1-6 was treated with two doses of adjuvanted (aluminium

hydroxide) hepatitis B vaccine (0.5 and 1 ?g protein per ml) and cell

integrity was measured after 24, 48 and 72 h. Hepatitis B vaccine

exposure increased cell apoptosis as detected by flow cytometry and

TUNEL assay. Vaccine exposure was accompanied by significant increases

in the levels of activated caspase 3, a key effector caspase in the

apoptosis cascade. Early transcriptional events were detected by

qRT-PCR. We report that hepatitis B vaccine exposure resulted in

significant upregulation of the key genes encoding caspase 7, caspase 9,

Inhibitor caspase-activated DNase (ICAD), Rho-associated coiled-coil

containing protein kinase 1 (ROCK-1), and Apoptotic protease activating

factor 1 (Apaf-1). Upregulation of cleaved caspase 3,7 were detected by

western blot in addition to Apaf-1 and caspase 9 expressions argues that

cell death takes place via the intrinsic apoptotic pathway in which

release of cytochrome c from the mitochondria triggers the assembly of a

caspase activation complex. We conclude that exposure of Hepa1-6 cells

to a low dose of adjuvanted hepatitis B vaccine leads to loss of

mitochondrial integrity, apoptosis induction, and cell death, apoptosis

effect was observed also in C2C12 mouse myoblast cell line after treated

with low dose of vaccine (0.3, 0.1, 0.05 ?g/ml). In addition In vivo

apoptotic effect of hepatitis B vaccine was observed in mouse liver.

2. Hepatitis B vaccination of male neonates and autism diagnosis, NHIS

1997-2002. <http://www.ncbi.nlm.nih.gov/pubmed/21058170>

Gallagher CM, Goodman MS.

J Toxicol Environ Health A. 2010;73(24):1665-77.

Universal hepatitis B vaccination was recommended for U.S. newborns in

1991; however, safety findings are mixed. The association between

hepatitis B vaccination of male neonates and parental report of autism

diagnosis was determined. This cross-sectional study used weighted

probability samples obtained from National Health Interview Survey

1997-2002 data sets. Vaccination status was determined from the

vaccination record. Logistic regression was used to estimate the odds

for autism diagnosis associated with neonatal hepatitis B vaccination

among boys age 3-17 years, born before 1999, adjusted for race, maternal

education, and two-parent household. Boys vaccinated as neonates had

threefold greater odds for autism diagnosis compared to boys never

vaccinated or vaccinated after the first month of life. Non-Hispanic

white boys were 64% less likely to have autism diagnosis relative to

nonwhite boys. Findings suggest that U.S. male neonates vaccinated with

the hepatitis B vaccine prior to 1999 (from vaccination record) had a

threefold higher risk for parental report of autism diagnosis compared

to boys not vaccinated as neonates during that same time period.

Nonwhite boys bore a greater risk.

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