PMID- 12388717
OWN - NLM
STAT- MEDLINE
DA  - 20021021
DCOM- 20021203
LR  - 20130418
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 76
IP  - 22
DP  - 2002 Nov
TI  - Immunization of macaques with formalin-inactivated respiratory syncytial virus
      (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV
      infection.
PG  - 11561-9
AB  - Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease 
      in infants and the elderly. RSV vaccine development has been hampered by results 
      of clinical trials in the 1960s, when formalin-inactivated whole-RSV preparations
      adjuvated with alum (FI-RSV) were found to predispose infants for enhanced
      disease following subsequent natural RSV infection. We have reproduced this
      apparently immunopathological phenomenon in infant cynomolgus macaques and
      identified immunological and pathological correlates. Vaccination with FI-RSV
      induced specific virus-neutralizing antibody responses accompanied by strong
      lymphoproliferative responses. The vaccine-induced RSV-specific T cells
      predominantly produced the Th2 cytokines interleukin-13 (IL-13) and IL-5.
      Intratracheal challenge with a macaque-adapted wild-type RSV 3 months after the
      third vaccination elicited a hypersensitivity response associated with lung
      eosinophilia. The challenge resulted in a rapid boosting of IL-13-producing T
      cells in the FI-RSV-vaccinated animals but not in the FI-measles virus-vaccinated
      control animals. Two out of seven FI-RSV-vaccinated animals died 12 days after
      RSV challenge with pulmonary hyperinflation. Surprisingly, the lungs of these two
      animals did not show overt inflammatory lesions. However, upon vaccination the
      animals had shown the strongest lymphoproliferative responses associated with the
      most pronounced Th2 phenotype within their group. We hypothesize that an
      IL-13-associated asthma-like mechanism resulted in airway hyperreactivity in
      these animals. This nonhuman primate model will be an important tool to assess
      the safety of nonreplicating candidate RSV vaccines.
AD  - Institute of Virology, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
      deswart@viro.fgg.eur.nl
FAU - De Swart, Rik L
AU  - De Swart RL
FAU - Kuiken, Thijs
AU  - Kuiken T
FAU - Timmerman, Helga H
AU  - Timmerman HH
FAU - van Amerongen, Geert
AU  - van Amerongen G
FAU - Van Den Hoogen, Bernadette G
AU  - Van Den Hoogen BG
FAU - Vos, Helma W
AU  - Vos HW
FAU - Neijens, Herman J
AU  - Neijens HJ
FAU - Andeweg, Arno C
AU  - Andeweg AC
FAU - Osterhaus, Albert D M E
AU  - Osterhaus AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Interleukin-13)
RN  - 0 (Respiratory Syncytial Virus Vaccines)
RN  - 0 (Vaccines, Inactivated)
RN  - 50-00-0 (Formaldehyde)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Asthma/etiology/pathology
MH  - Bronchial Hyperreactivity/etiology/pathology
MH  - *Formaldehyde
MH  - Humans
MH  - Immunization/*adverse effects
MH  - Interleukin-13/immunology
MH  - Lung/pathology
MH  - Macaca fascicularis
MH  - Respiratory Hypersensitivity/*etiology/pathology
MH  - Respiratory Syncytial Virus Infections/*immunology/prevention & control
MH  - Respiratory Syncytial Virus Vaccines/*adverse effects
MH  - Respiratory Syncytial Virus, Human/immunology
MH  - Vaccines, Inactivated/*adverse effects
PMC - PMC136757
OID - NLM: PMC136757
EDAT- 2002/10/22 04:00
MHDA- 2002/12/04 04:00
CRDT- 2002/10/22 04:00
PST - ppublish
SO  - J Virol. 2002 Nov;76(22):11561-9.