The hepatitis B vaccine (HBV) is administered to more than 70% of neonates worldwide. Whether this neonatal vaccination affects brain development is unknown.
HBV induced impaired behavioral performances…
At 6w, there was decreased neurogenesis, M1 microglial activation and a neurotoxic profile of neuroimmune molecule expression… in the hippocampus of the HBV-vaccinated mice.
These findings suggest that neonatal HBV vaccination of mice results in neurobehavioral impairments in early adulthood…
Perinatal immune activation has been demonstrated to influence brain development and behavior. The brain is still developing in the early postnatal time period and thus immune activation can impact the developmental programming of the brain.
[E]arly vaccination with HBV, which induces strong immune activation, is suspected to influence brain development and behavior.
HBV that we used contained HBsAg [Hepatitis B surface antigen] and an aluminum adjuvant. Immunization with a protein antigen with an aluminum adjuvant, such as the HEL [hen egg lysozyme] in alum, primarily drives the Th2 response.
In agreement with the HBV results, neonatal HEL /alum injection… impaired spatial cognition and increased anxiety-related behavior…
Cytokines and neurotrophins can mediate the effects of peripheral immune activation on the CNS.
Under physiological conditions IFN-γ [interferon-gamma] exerts a neurobeneficial role, including elevating levels of neurogenesis and inducing neuronal differentiation, whereas TNF-α [tumor necrosis factor-alpha] has a detrimental effect on many neurobehavior processes.
In this study, we found that there were reduced levels of IFN-γ and increased levels of TNF-α in the hippocampi of HBV-mice… These findings suggest that HBV induced a profile of cytokine expression in the hippocampus, which may be neurodetrimental.
Microglia can be activated into two different phenotypes: the M1 and M2 phenotypes. Classically activated M1 microglia produce proinflammatory cytokines and affect neuro- genesis and neuronal activities, whereas alternatively activated M2 microglia exert neuroprotective effects primarily through anti-inflammatory molecules and neurotrophins. This study verified that neonatal HBV vaccination skewed the microglia towards the M1 phenotype.
[T]hese results suggested that the neurobehavioral impairments were associated with microglial activation…
HBV’s behavioral effects are only detectable at the age of early adulthood… These findings suggest that the vaccine’s influence on behavior has a latency period prior to emergence…
This work provides innovative data supporting the long suspected potential association of HBV with certain neuropsychiatric disorders such as autism and multiple sclerosis.