h ac a, N .Y . Ab stract. T hirty-two of 51 catt le infected with Mycobacterium paratub ercu los is ha dchro nic e nte riti s , chro nic lymp hangiti s o r me senter ic lym p hade no p a th y , or a ll three , at sla ug hte r. G ran ulom a tous inflammato ry le sion s were mi ld to a d va nce d a nd predominant ly invol ve d t he dista l sma ll in testi ne . Re ctal invo lveme nt wa s see n on ly in five ca tt le . Fourteen ha d microgran ulom as in the live r . There were t hree cytologica l form s o f macrop hage s : hist ioc ytic , po lygon al a nd e p it he lio id . T he la tt e r two types ha d engulfed mode rate num be rs of acid-fast b aci lli. T he h ist io cytic m acro p hages usua lly were packed with ac id-fast bacilli. Except in th e live r a nd occasiona lly its node s , remote le sio ns of para tubercu lo sis were no t found in ot her orga ns. One animal had endocardial a nd ao rt ic ca lcification s. Most catt le with sig ns of diarr hea ha d glo bule leu ko cytes in or around mye nteric ganglio n ce lls . T he thymus of 3-to 8-year-o ld catt le wit h clinical signs freq uent ly had mi ld to a d va nce d involut ion . T he th ym us of sim ila r ly aged infected a n ima ls without clin ica l signs, a nd of pa ratu be rc ulos is-nega tive animals , ha d no t involuted .Parat ube rc ulosis (Jo hne's disease ) , a chro nic infectio us disease of do mes ticated and wild rum inant s, has been recognized t hro ug ho ut the world since it first was descri bed in 1895 . Its ca usat ive agen t is Mycobacterium paratuberculosis, a faculta tive intracellul a r acid-fast bacte rium . T he macroscopic a nd hist ol ogic lesion s of pa ratubercul o sis basically remain confined to th e in tes ti ne , mesenteric and ileocaecall ymph nodes [7] . A lt ho ug h M . paratuberculosis has been cultured from a variety o f othe r orga ns , microscopic lesio ns have been found o nly in th e live r [1 2] . M . paratuberculosis is ass umed to sprea d prim a rily via circulati ng macrophages. In the liver th ese macro ph ages ma y become foca lly tra pped in sin usoi ds a nd with lymphocytes ma y give rise to micr ogr anulo mas .Early inves tiga tors of par atubercul osis e mp has ize d its similarity to leprosy [3 , 5 , 10] . Bo th diseases are ca use d by acid-fas t bacte ria th at a re diff icult to culture a nd hav e lon g gro wth periods . T he inflamm at o ry response in both d iseases is similar. Despite invo lveme nt of differe nt orga n syste ms, th e micro scopic lesion s a re dom inated by macr oph ages an d Lan gh an s' gia nt ce lls .Le prosy has bee n classified int o two po la r fo rms -tube rcul o id an d leprom at ou s 19 6

We have previously reported that Vivax Malaria Protein 001 (VMP001), a vaccine candidate based on the circumsporozoite protein of Plasmodium vivax, is immunogenic in mice and rhesus monkeys in the presence of various adjuvants. In the present study, we evaluated the immunogenicity and efficacy of VMP001 formulated with a TLR9 agonist in a water-in-oil emulsion. Following immunization, the vaccine efficacy was assessed by challenging Aotus nancymaae monkeys with P. vivax sporozoites. Monkeys from both the low- and high-dose vaccine groups generated strong humoral immune responses to the vaccine (peak median titers of 291,622), and its subunits (peak median titers to the N-term, central repeat and C-term regions of 22,188; 66,120 and 179,947, respectively). 66.7% of vaccinated monkeys demonstrated sterile protection following challenge. Protection was associated with antibodies directed against the central repeat region. The protected monkeys had a median anti-repeat titer of 97,841 compared to 14,822 in the non-protected monkeys. This is the first report demonstrating P. vivax CSP vaccine-induced protection of Aotus monkeys challenged with P. vivax sporozoites.

The immune response of cattle to nonliving vaccines derived from Brucella abortims rough strain 45/20 was studied. Vaccines contained trehalose dimycolate and a derivative of muramyl dipeptide, N-acetylmuramyl-L-cx-aminobutyryl-Disoglutamine. A factorial experiment was designed to test the effects of type of antigen, quantity of antigen, and quantity of mineral oil on the immune response to porin. Muramyl dipeptide was kept constant at 5 mg per dose, and 1 part of trehalose dimycolate was incorporated for two parts of dry matter. Over a 10-week period, blastogenesis responses to porin were largest in cattle immunized with outer membranes; the highest antibody titers to the porin-lipopolysaccharide complex were achieved by immunization with detergent-extracted outer membrane proteins. There was no advantage in the use of 25, rather than 5, mg of any of the antigens, but antibody responses were improved by increasing the quantity of oil from 0.6 to 1.8 ml per dose. In other animals, blastogenesis and antibody responses were sustained at high levels longer than 3 months after two vaccinations with outer membrane proteins. Intradermal injection of porin evoked inflammatory reactions histologically consistent with delayed-type hypersensitivity. Cross-reactions in cases of delayed-type hypersensitivity occurred with porin derived from a smooth strain of B. abortils but were less extensive than in the blastogenesis test. The magnitude of the delayed-type hypersensitivity and blastogenesis responses induced by vaccination exceeded those observed after natural or experimental infections. No ill effects were observed after vaccination. These findings provide a basis for the use of trehalose dimycolate and muramyl dipeptide adjuvants in evaluating nonviable vaccines for bovine brucellosis.Development of an effective nonviable vaccine for Brlcella abortus would constitute a major advance toward the goal of eradicating bovine brucellosis from the United States. It is well established that B. abortus is a facultative intracellular parasite for which a cell-mediated immune response associated with delayed-type hypersensitivity (DTH) is crucial for protective immunity (8,14). Such a response can be induced effectively by nonviable vaccines in which trehalose dimycolate (TDM) and muramyl dipeptide (MDP) have been incorporated as adjuvants (for reviews, see references 1 and 7). Woodard et al. (25) have demonstrated that guinea pigs immunized with killed cells of B. t Present address: Syncor International Corp., Berkeley. CA 94710.abortus rough strain 45/20 combined with both TDM and MDP adjuvants developed a relatively high level of resistance to infection with virulent B. abortuls 2308. The use of these adjuvants would be feasible in a commercial vaccine for cattle because the absence of mycobacteria and the low content of mineral oil minimize local reactions and prevent development of tuberculin hypersensitivity.We have isolated and characterized the major outer membrane proteins (OMP) of B. abortlls (21). One of these (group 2)...

Cure of female cattle with venereal vibriosis by systemic immunization with killed Campylobacter fetus cells in incomplete Freund adjuvant was investigated. Heifers infected in the cervicovaginal area with a cloned population of C. fetus venerealis were vaccinated subcutaneously 14 and 24 days thereafter with the infecting strain in incomplete Freund adjuvant. Six of eight vaccinated heifers were free of infection 25 to 48 days postinfection. One of the cured animals had an intercurrent infection which precluded interpretation of a vaccine effect. All controls remained infected 48 to 51 days postinfection, when the experiment was terminated. In vaccinated animals, agglutination titers against whole cells of the infecting strain reached peaks varying from 1,280 to 20,480 in serum and from 20 to 5,120 in cervicovaginal mucus (CVM) within days 24 to 32 postinfection. No consistent relationship was noted between levels of whole cell antibodies in serum and those in CVM. Evidence for the occurrence of antigenic variation in the organism after vaccination was sought by comparing the agglutinability of the infecting strain and CVM isolates in serum and CVM extracts. Serum samples of most cured heifers agglutinated whole cells prepared from isolates of the respective heifers to the same extent as cells of the infecting strain. In the corresponding comparisons, those from noncured animals agglutinated isolates to lower titers. CVM extracts from one cured animals agglutinated isolates derived from the same or closely spaced CVM samples to titers comparable with those obtained with the infecting strain. In the remaining animals, CVM extracts which agglutinated the infecting strain produced lower or undetectable reactions with corresponding isolates. It is proposed that the elimination of infection is dependent upon opposing responses of host and parasite, of which the degree of antigenic alteration in the infecting strain and the rate of mobilization and the concentration of specific antibodies in the genital secretions are key factors.