An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitisvirus vaccine

The live attenuated vaccine strain of Venezuelan equine encephalitis virus (VEEV), TC-83, protects mice against challenge (subcutaneous and aerosol) w ith virulent VEEV but is not suitable for widescale human use. Elucidation of the immune response profile of protected mice should assist in the devel opment of an improved vaccine. We determined the optimum dose of TC-83 requ ired to consistently protect Balb/c mice from airborne challenge with the v irulent Trinidad Donkey strain of VEEV and studied the development of humor al and cellular immune responses in protected mice between 6 h and 21 days postvaccination. The most dramatic immune responses occurred in draining ly mph nodes 24 h following vaccination with increased levels of activated B c ells and T cells of both CD4(+) and CD8(+) subtypes. Activated monocyte/mac rophages and natural killer cells were also seen between 6 h and 7 days pos t-vaccination. Serum contained detectable VEEV-specific IgG on day 5 postva ccination with titres continuing to rise on days 7, 14 and 21. Isotypes of IgG measured on days 7 and 21 were predominantly of the IgG2a subclass, ind icating that the immune response was Th1-mediated. Cytokine mRNA was quanti fied by RT-PCR and revealed production of the Th1 cytokine IFN-gamma and th e inflammatory cytokine TNF-alpha, whereas the Th2 cytokine IL4 was not det ected above control levels at any of the time points studied. This data des cribes key cellular immune responses at early times post-vaccination and is consistent with previous data demonstrating protection against aerosol cha llenge with VEEV in the absence of detectable levels of specific IgG or IgA antibody. Crown Copyright (C) 2000 Published by Elsevier Science Ltd. All rights reserved.