Brucellosis 2003 proceedings - PHIDIAS

Short Oral Communications
Vaccines
VO6- PASSIVE TRANSFER OF PROTECTION AGAINST Brucella melitensis 16M
INFECTION IN A MURINE MODEL .
Mina J. Izadjoo 1 , Richard H. Borschall 2 , Apurba K. Bhattacharjee 2 , Mikeljon P. Nikolich 2 , Ted L.
Hadfield 1 , and David L. Hoover 2 . (1) Armed Forces Institute of Pathology, Washington D.C, USA. (2)
Walter Reed Army Institute of Research, Forest Glen, Maryland, USA.
Immunization with Brucella melitensis WR201, a live, attenuated purine
auxotroph, protects mice against intranasal challenge with B. melitensis 16M. We
have previously shown that passive transfer of antibody or adoptive transfer of T cells
from mice immunized with WR201 protects Balb/c mice against intranasal challenge
with B. melitensis 16M. To determine the relative role of antibody directed against
surface O-polysaccharide (OPS) vs. antibody directed against non-OPS components,
we immunized BALB/c mice with WR201 or WRR51, a rough, wboA mutant of 16M,
collected serum 8 weeks later and purified IgG using a protein A/G column. IgG was
transferred to naïve BALB/c mice, which were then challenged intranasally with 16M.
IgG from mice immunized with WR201, but not from mice immunized with WRR51,
protected mice. To further elucidate the protection against Brucella melitensis 16M
infection in mice, we did passive transfer of immune nonhuman primate sera to mice
and demonstrated protective effects. Data from these studies demonstrate that
antibody is an important immune correlate of protection against infection with
Brucella and demonstrate the utility of our mouse model to screen candidate
vaccines in development.
VO7- ORAL IMMUNIZATION WITH WR201, A LIVE, ATTENUATED PURINE
AUXOTROPHIC STRAIN OF B. melitensis, PROTECTS MICE AND NONHUMAN
PRIMATES AGAINST RESPIRATORY CHALLENGE WITH B. melitensis 16M.
D. Hoover 1 , M. Izadjoo 2 , R. Borschel 1 , M. Mense 1 , A. Bhattacharjee 1 and C. Paranavitana 1 . (1) Walter
Reed Army Institute of Research, (2) Armed Forces Institute of Pathology, Washington, DC, USA.
Vaccination could provide protection for humans threatened by deliberate use
of aerosolized Brucella as a bioweapon, which could infect via the respiratory tract
and the conjunctiva. Successful vaccine development will require use of models of
immunization and challenge by a relevant route, and finding the appropriate balance
between safety and protective efficacy. To address these issues, we have orally
immunized mice and Rhesus macaques with B. melitensis WR201, a purine
auxotroph created by deletion of purEK from B. melitensis 16M, and challenged them
intranasally (mice) or via aerosol (monkeys). Mice given 10 11 CFU of WR201 became
systemically infected. Infection cleared from nearly all animals by 8 weeks postimmunization.
Immunization led to dose-related increases in anti-LPS serum
antibody and to production of IL-2 and IFN-γ by spleen cells cultured with Brucella
antigens. Approximately 70% of mice were protected against disseminated infection
after intranasal challenge; protection depended on immunizing dose and viability of
immunizing organisms. Immunization also led to accelerated clearance of bacteria
from the lungs of challenged animals. WR201 was also highly attenuated when given
orally to Rhesus macaques, although low numbers of bacteria persisted in lymph
nodes 8 weeks after immunization. Immunized monkeys developed serum anti-LPS
Brucellosis 2003 International Research Conference
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