nated mice were protected against infection by tick- 
borne Borrelia, and further that spirochetes were 
eliminated from infected ticks. This has made possi- 
ble an epidemiologic study of the efficacy of protec- 
tive immunity, since ticks can be collected in the 
wild and their ability to infect laboratory mice as- 
sayed. Although the results from any individual tick 
cannot be directly evaluated, the analysis of suffi- 
ciently large numbers of ticks will provide a statisti- 
cal sample that will test the efficacy of the vaccine 
in wild ticks. The first such study has been per- 
formed using ticks from Nantucket. Vaccination 
with OspA or OspB was effective against infection 
with wild ticks; and again the spirochetes were elim- 
inated from infected ticks. These studies are now 
being extended to ticks from other locations. It 
should therefore be possible to predict the breadth 
of protection that can be afforded by OspA and 
OspB, prior to human clinical studies. 
Research in the past year has also focused on 
mechanisms whereby the spirochete evades protec- 
tive immunity. Spirochetes have been identified in 
which one mechanism of evasion appears to be trun- 
cation of the OspB polypeptide. As Dr. Flavell's 
group showed previously for OspA, neutralizing de- 
terminants on OspB are found near the carboxyl ter- 
minus. A mutant form of B. burgdorferi strain N40 
has a truncated OspB that permits escape from im- 
mune surveillance in vaccinated mice, in contrast to 
wild-type Borrelia, which lacks this truncation. Fur- 
thermore, live spirochetes recovered from vacci- 
nated mice show alterations in outer surface pro- 
teins. These are now being characterized. (Grants 
from the National Institutes of Health, the Centers 
for Disease Control, and the Mathers Foundation 
provided partial support for the project described 
above.) 
Dr. Flavell is also Professor of Immunobiology 
at Yale University School of Medicine. 
Books and Chapters of Books 
Flavell, R.A., and Geiger, T. 1992. T cell tolerance 
to peripherally expressed antigens studied in 
transgenic mice. In Annual of Cardiac Surgery 
(Yacoub, M., and Pepper, J., Eds.). London: 
Current Science, pp 17-20. 
Geiger, T., Gooding, L., Hanahan, D., and Flavell, 
R.A. 1991. T cell tolerance to peripherally ex- 
pressed antigens studied using transgenic mice. 
In HLA-B27* Spondyloarthropathies (Lipsky, 
P.E., and Taurog, J.D., Eds.). New York: Elsevier 
Science, pp 13-19. 
Articles 
Berland, R., Fikrig, E., Rahn, D., Hardin, J., and Fla- 
vell, R.A. 1991. Molecular characterization of 
the humoral response to the 4l-kDa flagellar anti- 
gen of Borrelia burgdorferi, the Lyme disease 
agent. Infect Immun 59:3531-3535. 
Chang, C.-H., Hammer, J., Loh, J.E., Fodor, W.L., 
and Flavell, R.A. 1992. The activation of major 
histocompatibility complex class I genes by inter- 
feron regulatory factor 1 (IRF-1). Immunogenet- 
ics 35:378-384. 
de Souza, M.S., Fikrig, E., Smith, A.L., Flavell, R.A., 
and Barthold, S.W. 1992. Nonspecific prolifera- 
tive responses of murine lymphocytes to Borrelia 
burgdorferi antigens . / Infect Dis 165:471-478. 
Fikrig, E., Barthold, S.W., Kantor, F.S., and Flavell, 
R.A. 1991. Protection of mice from Lyme borre- 
liosis by oral vaccination with Escherichia coli 
expressing OspA. f Infect Dis 164:1224-1227. 
Fikrig, E., Barthold, S.W., Kantor, F.S., and Flavell, 
R.A. 1992. Long-term protection of mice from 
Lyme disease by vaccination with OspA. Infect 
Immun 60:11^-111 . 
Fikrig, E., Barthold, S.W., Marcantonio, N., Deponte, 
K., Kantor, F.S., and Flavell, R.A. 1992. Roles of 
OspA, OspB, and flagellin in protective immunity 
to Lyme borreliosis in laboratory mice. Infect Im- 
mun 60:657-661 . 
Fikrig, E., Barthold, S.W., Persing, D.H., Sun, X., 
Kantor, F.S., and Flavell, R.A. 1992. Borrelia 
burgdorferi strain 25015: characterization of 
outer surface protein A and vaccination against 
infection, f Immunol 148:2256-2260. 
Fikrig, E., Huguenel, E.D., Berland, R., Rahn, D.W., 
Hardin, J.A., and Flavell, R.A. 1992. Serologic 
diagnosis of Lyme disease using recombinant 
outer surface proteins A and B and flagellin. //w- 
fect Dis 165:1127-1132. 
Fikrig, E., Telford, S.R., III, Barthold, S.W., Kantor, 
F.S., Spielman, A., and Flavell, R.A. 1992. Elimi- 
nation of Borrelia burgdorferi from vector ticks 
feeding on OspA-immunized mice. Proc Natl 
Acad Sci USA 89:5418-5421. 
Geiger, T., Gooding, L.R., and Flavell, R.A. 1992. 
T-cell responsiveness to an oncogenic peripheral 
protein and spontaneous autoimmunity in trans- 
genic mice. Proc Natl Acad Sci USA 89:2985- 
2989. 
Loh, J.E., Chang, C.-H., Fodor, W.L., and Flavell, 
R.A. 1992. Dissection of the interferon7-MHC 
class II signal transduction pathway reveals that 
type I and type II interferon systems share com- 
mon signalling component(s) . EMBO /11:1351- 
1363. 
IMMUNOLOGY 329 
