A SPECIAL RFD EXTRA!: Vaccine Safety: Pathogenesis of Virus Vaccine Neurotoxicity

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A SPECIAL RFD EXTRA!

 

 

We’ve issued a special RFD EXTRA! due to the importance of this document:

 

An FDA Study: The Pathogenesis Of Virus Vaccine Neurotoxoicty

RAT MODEL OF AUTISM USING NEONATAL INFECTION WITH NEUROTROPIC VIRUSES REVEALS

AUTISTIC-LIKE CHANGES IN NEUROANATOMY, NEUROCHEMISTRY, NEUROLOGICAL DISEASE AND

BEHAVIOR

Administering insufficiently attenuated vaccines to infants may place the

child’s CNS at increased risk for injury. Thus, it is imperative to develop

methods of pre-clinical neurovirulence testing with which to predict which

vaccines might have significant neurovirulence potential for human CNS

 

 

 

 

http://www.fda.gov/cber/research/0200706.htm

 

 

Vaccine Safety: Pathogenesis of Virus Vaccine Neurotoxicity

Principal Investigator

K. M. Carbone

Laboratory

Laboratory of Pediatric and Respiratory Viral Diseases; Division of Viral

Products; Office of Vaccines Research and Review

Project Summary

Since the developing nervous system is uniquely sensitive to damage following

virus infection, postnatal CNS development during the first several years of

life provides for continued susceptibility of the infant CNS to damage by viral

infection after birth. Administering insufficiently attenuated vaccines to

infants may place the child's CNS at increased risk for injury. Thus, it is

imperative to develop methods of pre-clinical neurovirulence testing with which

to predict which vaccines might have significant neurovirulence potential for

human CNS.

Thus, it is important to develop valid molecular biological, in vitro and in

vivo models to evaluate the pathogenesis of the neurotoxic effects of vaccine

viruses. Development of these models will lead to improved safety of childhood

vaccines, cost saving and improved predictability of neurovirulence testing, and

information obtained in these studies will be useful in testing potentially

neurovirulent vaccines (e.g., measles, mumps, HIV, parainfluenza, Japanese

encephalitis).

Progress: 2001 CBER Outstanding Regulatory Research Project

 

Molecular Markers of Neurotoxicity: We have identified vaccine virus-related

perturbations in CNS gene expression by standard semiquantitative RT-PCR and by

differential display techniques, including endogenous immune mediators of the

CNS. We have recovered un-characterized gene products from new genes that are

altered by virus infection of the brain. We have initiated RPA to compare

changes in endogenous immune mediators in the CNS in animals infected with low

and high neurovirulence strains of mumps virus.

 

 

Animal Models of CNS Diseases Following Childhood Virus Infection: Autism.

Viruses are known etiologic agents of autism (e.g., rubella). Therefore,

concerns are raised regarding a possible relationship between childhood vaccines

and autism. Because no valid animal models existed to study the pathogenesis of

the neuroanatomical and behavioral signs of autism, we developed a rat model of

autism using neonatal infection with neurotropic viruses. We have characterized

autistic-like changes in neuroanatomy, neurochemistry, neurological disease and

behavior in these rats. In addition, we have identified regional and

developmental changes in neurotransmitters, including serotonin and

norepinephrine. A developmental study of damage to developing brain (e.g.,

cerebellum) in virus infected rats was performed demonstrating anatomical,

behavioral and neurological consequences.

 

Publications

 

J Virol 1998 Oct;72(10):8037-42

Comparison of the neurovirulence of a vaccine and a wild-type mumps virus strain

in the developing rat brain.

Rubin SA, Pletnikov M, Carbone KM

Pub Med

 

 

J Vet Diagn Invest 1998 Oct;10(4):338-43

Clinical, serologic, and histopathologic characterization of experimental Borna

disease in ponies.

Katz JB, Alstad D, Jenny AL, Carbone KM, Rubin SA, Waltrip RW 2nd

Pub Med

 

 

Behav Brain Res 1999 Apr;100(1-2):43-50

Developmental brain injury associated with abnormal play behavior in neonatally

Borna disease virus-infected Lewis rats: a model of autism.

Pletnikov MV, Rubin SA, Vasudevan K, Moran TH, Carbone KM

Pub Med

 

 

Brain Res Bull 1999 Jan 1;48(1):23-30

Borna disease virus-induced hippocampal dentate gyrus damage is associated with

spatial learning and memory deficits.

Rubin SA, Sylves P, Vogel M, Pletnikov M, Moran TH, Schwartz GJ, Carbone KM

Pub Med

 

 

J Infect Dis 1999 Aug;180(2):521-525

The Mumps Virus Neurovirulence Safety Test in Rhesus Monkeys:A Comparison of

Mumps Virus Strains.

Rubin SA, Snoy PJ, Wright KE, Brown EG, Reeve P, Beeler JA, Carbone KM

Pub Med

 

 

Physiol Behav 1999 Jul;66(5):823-31

Persistent neonatal Borna disease virus (BDV) infection of the brain causes

chronic emotional abnormalities in adult rats.

Pletnikov MV, Rubin SA, Schwartz GJ, Moran TH, Sobotka TJ, Carbone KM

Pub Med

 

 

J Virol 2000 Jun 1;74(11):5382-5384

Evaluation of a Neonatal Rat Model for Prediction of Mumps Virus Neurovirulence

in Humans.

Rubin SA, Pletnikov M, Taffs R, Snoy PJ, Kobasa D, Brown EG, Wright KE, Carbone

KM

Pub Med

 

 

Dev Brain Res 2000 Feb 7;119(2):179-85

Effects of neonatal rat Borna disease virus (BDV) infection on the postnatal

development of the brain monoaminergic systems.

Pletnikov MV, Rubin SA, Schwartz GJ, Carbone KM, Moran TH

Pub Med

 

 

Ann N Y Acad Sci 2001 Jun;939:318-9

Rat model of autism spectrum disorders. Genetic background effects on Borna

disease virus-induced developmental brain damage.

Pletnikov MV, Jones ML, Rubin SA, Moran TH, Carbone KM

Pub Med

 

 

Clin Microbiol Rev 2001 Jul;14(3):513-27

Borna disease virus and human disease.

Carbone KM

Pub Med

 

 

Mol Psychiatr 2000 Nov;5(6):577

Borna again, starting from the beginning.

Carbone KM, Pletnikov M

Pub Med

 

 

Ann Clin Biochem 2001 Jul;38(Pt 4):348-55

Synthetic peptide-based electrochemiluminescence immunoassay for anti-Borna

disease virus p40 and p24 antibodies in rat and horse serum.

Yamaguchi K, Sawada T, Yamane S, Haga S, Ikeda K, Igata-Yi R, Yoshiki K,

Matsuoka M, Okabe H, Horii Y, Nawa Y, Waltrip RW 2nd, Carbone KM

Pub Med

 

 

Brain Res Dev Brain Res 2001 Jan 31;126(1):1-12

Neonatal Borna disease virus infection (BDV)-induced damage to the cerebellum is

associated with sensorimotor deficits in developing Lewis rats.

Pletnikov MV, Rubin SA, Carbone KM, Moran TH, Schwartz GJ

Pub Med

 

 

Curr Opin Microbiol 2001 Aug;4(4):467-75

Borna disease: virus-induced neurobehavioral disease pathogenesis.

Carbone KM, Rubin SA, Nishino Y, Pletnikov MV

Pub Med

 

 

 

 

 

Last Updated: 4/1/2002

 

 

 

 

 

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