Yeast-expressed Puumala hantavirus nucleocapsid protein induces protection in a bank vole model

Hantaviruses are rodent-borne agents that cause severe human diseases. The coding sequences for the authentic and a His-tagged Puumala hantavirus (PUUV) nucleocapsid (N) protein were expressed in yeast (Saccharomyces cerevisiae). N-specific monoclonal antibodies demonstrated native antigenicity of the two proteins. All bank voles vaccinated with the His-tagged N protein in Freund's adjuvant (n=12) were defined as completely protected against subsequent virus challenge, based on the absence of viral N protein, RNA and G2-specific antibodies. In the group vaccinated with the yeast-expressed authentic N protein in Freund's adjuvant, 2/6 animals were defined as completely protected and 4/6 as partially protected. Moreover, when animals were vaccinated with the His-tagged N protein in an adjuvant certified for human use (alum), all (n=8) were at least partially protected (six completely, two partially). The general advantages of the yeast expression system make the described recombinant proteins promising candidate vaccines against hantavirus infection.     

Dietary fat during pregnancy and lactation increases milk fat and insulin-like growth factor I concentrations and improves neonatal growth rates in swine

Primiparous (n = 24) and multiparous (n = 24) sows were used to examine the effects of supplemental dietary fat and induction of parturition (d 112) on colostrum and milk composition and suckling piglet growth. Sows were assigned to one of eight treatments on d 90 of gestation that included variables such as parity (1 vs. >/=3), dietary fat (0 vs. 10%), and farrowing (natural vs. induction via lutalyse on d 112). Piglets suckling fat-supplemented dams grew up to 25% faster than control pigs nursing unsupplemented sows (250 vs. 200 g/d; P < 0.01). Improved growth was correlated with elevated milk fat and insulin-like growth factor (IGF) concentrations associated with fat supplementation. Dietary fat elevated milk fat concentration at 48 and 72 h postfarrowing by 21.6 and 22.6%, respectively (P < 0.05). Compared with nonfat-fed controls, multiparous sows fed 10% fat showed a more consistent rise in milk fat concentration, with 26% and 41% elevations for induced or naturally farrowing sows, respectively, vs. a 19% reduction or a 1% elevation in induced or naturally farrowing gilts (P < 0.01). The concentration of milk IGF-I tended to be lower in gilts than in multiparous sows (P < 0.2, 95.7 vs. 117.4 microg/L), and levels were particularly low in milk from induced gilts receiving no additional dietary fat (44.7 microg/L). However, fat supplementation elevated IGF-I to levels (110.6 microg/L) exceeding those measured in unsupplemented, naturally farrowing control sows and gilts (95.8 microg/L). In conclusion, supplemental dietary fat elevates milk fat in multiparous sows more than primiparous gilts regardless of farrowing treatment (induced vs. natural farrowing) and improves piglet growth throughout lactation irrespective of parity or farrowing treatment. The potential of supplemental dietary fat to reverse the reductions in milk IGF-I observed in first-parity females and in dams induced to farrow merits further investigation.     

Effect of porcine zonae pellucidae immunisation on ovarian follicular development and endocrine function in domestic ewes (Ovis aries)

Domestic ewes (Ovis aries) were immunised with porcine zonae pellucidae (pZP) or pZP conjugated to keyhole limpet haemocyanin (KLH) in adjuvant(s) to examine the feasibility of the species to serve as a model for further development of pZP-based vaccines in ungulates. Two immunisation groups were employed, with a third group receiving only adjuvant (n = 5 per group). Early in the study, oestrous activity was monitored by the use of a vasectomised ram fitted with a marking harness. Eventually, ewes were exposed to an intact ram for breeding. In addition, weekly serum and every-other-day faecal samples were collected to measure pZP antibodies and progesterone metabolite concentrations respectively. At the conclusion of the study, fecundity was established, and ovarian tissue was examined. Ewes immunised against pZP : KLH with adjuvant produced minimal antibody absorbance levels, displayed normal oestrous cycles, became pregnant upon introduction of the intact ram and exhibited normal ovarian histopathology. Ewes immunised against pZP with adjuvant produced high antibody absorbance levels, were acyclic following primary immunisation and were infertile. Examination of the ovarian tissue revealed atrophic changes that included: (1) the absence of growing follicles; (2) significant reduction in the number of primordial follicles; and (3) the presence of abnormal granulosa cell clusters lacking oocytes. Antisera displayed immunoreactivity to the major components of pZP, and immunohistochemical labelling of ovarian tissue showed specificity to the ZP. These data are the first generated in an ungulate species showing deleterious effects of pZP immunisation on folliculogenesis and oestrous cyclicity.     

QS-21 promotes an adjuvant effect allowing for reduced antigen dose during HIV-1 envelope subunit immunization in humans

Three separate studies were undertaken in HIV-1 uninfected persons to determine if the adjuvant QS-21 improves the magnitude or kinetics of immune responses induced by recombinant soluble gp120 HIV-1(MN) protein (rsgp120) immunization. The QS-21 was administered at two doses (50 and 100 microg), either alone or in combination with aluminum hydroxide (600 microg). At the highest doses of rsgp120 (100, 300, and 600 microg), QS-21 exerted no significant effect on either binding or neutralizing antibody titers. Antibody binding and neutralizing responses fell dramatically when rsgp120, formulated with alum alone, was given at low doses (3 and 30 microg). In contrast, antibody responses similar in titer to those in the high dose antigen groups were induced with the low dose rsgp120 formulated with QS-21. In addition, the lymphocyte proliferation and delayed type hypersensitivity skin testing were superior in the QS-21 recipients compared with the alum recipients at the low antigen doses. Moderate to severe pain was observed in majority of the volunteers receiving QS-21 formulations, and vasovagal episodes and hypertension were not infrequent. Thus, the use of QS-21 may provide a means to reduce the dose of a soluble protein immunogen.     

Humoral defence improvement and haematopoiesis stimulation in sows and offspring by oral supply of shark-liver oil to mothers during gestation and lactation

Shark-liver oil (SLO) contains two bioactive lipids: alkylglycerols and n-3 PUFA. Alkylglycerols have immunostimulating and haematopoietic properties, while n-3 PUFA are essential for optimal neonatal development. We investigated the beneficial effects of dietary supplementation with 32 g SLO/d to twelve pregnant and then lactating sows (from day 80 of pregnancy to weaning) on the growth and immune status of their offspring, compared with a control group. Sows were vaccinated against Aujeszky's disease 21 d before term. Blood samples were collected from sows before treatment, on delivery and 14 d later, and from five piglets per litter on days 2, 21 and 36 after birth; colostrum and milk samples were collected 12 h, 14 and 28 d postpartum. Compared with controls, supplemented sows had higher levels of both erythrocytes and Hb in their blood, and higher concentrations of IgG, alkylglycerols and n-3 PUFA in their mammary secretions. In piglets from supplemented sows, leucocytes and IgG were higher. Supplementation with SLO resulted in an increase in Aujeszky antibodies in both blood and colostrum of sows after vaccination, together with an increase in Aujeszky antibodies in piglet blood. Our findings demonstrate that improvement of both passive and active immune status in piglets is related to the consumption of alkylglycerols associated with n-3 PUFA in the sow diet. The overall improvement in offspring health status by SLO supplementation to the mother could be of interest for optimisation of the lipid diet during and after pregnancy.     

Serum antibody immunoreactivity and safety of native porcine and recombinant zona pellucida vaccines formulated with a non-Freund’s adjuvant in horses

Commercial and regulatory limitations associated with native porcine zona pellucida (pZP) vaccines formulated with Freund’s adjuvants may be overcome by developing effective recombinant ZP vaccines (reZP) and identifying alternative adjuvant formulations. A two-part preparatory study used 15 geldings and identified potentially effective alternative adjuvant formulations based on anti-pZP antibody response following treatment with pZP formulated with Addavax (AddaVax ?, Invivogen), Quil A (Quil-A® Adjuvant, Invivogen), Quil A and Poly (I:C) (HMW VacciGrade?, Invivogen), Pet Gel A (Montanide? Pet Gel A, Seppic) and Pet Gel A and Poly (I:C). Injection site reactions, rectal temperature and respiratory and heart rates were also monitored for three days post-treatment. Suitable anti-pZP antibody titres were seen in response to Pet Gel A and Pet Gel A and Poly (I:C). Subsequently in 31 mares, following administration of pZP, reZP and a combination of pZP and reZP proteins prepared in Pet Gel A and Poly (I:C), both serum anti-pZP and -reZP antibody responses were monitored. In addition, safety was assessed for up to seven days post-treatment by inspection and palpation of gluteal intramuscular injection sites and measurement of rectal temperature. The measured antibody titres in all treatment groups differed significantly to an adjuvant control group (P?<?0.001). Temporal changes in both anti-pZP and -reZP antibody titres in all ZP treatment groups were similar to patterns reported previously in various species vaccinated with pZP formulated with Freund’s adjuvants. There were no differences in anti-pZP antibody titres between the pZP and reZP treated groups (P?>?0.05). Side effects were mild and transient in nature. This represents the first application of a reZP vaccine formulated with non-Freund’s adjuvants evoking a similar antibody titre response to native pZP vaccination in mares.     

Protection against transplacental transmission of moderately virulent classical swine fever virus using live marker vaccine “CP7_E2alf”

Classical swine fever (CSF) remains as one of the most important infectious diseases of swine. While prophylactic vaccination is usually prohibited in free countries with industrialized pig production, emergency vaccination is still foreseen. In this context, marker vaccines are preferred as they can reduce the impact on trade.The live-attenuated Suvaxyn® CSF Marker vaccine by Zoetis (based on pestivirus chimera “CP7_E2alf”), was recently licensed by the European Medicines Agency. Its efficacy for the individual animal had been shown in prior studies, but questions remained regarding protection against transplacental transmission. To answer this question, a trial with eight pregnant sows and their offspring was performed as prescribed by the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Six of the sows were intramuscularly vaccinated on day 44 of gestation, while the other two remained as unvaccinated controls. All sows were challenged with the moderately virulent CSFV strain ”Roesrath” and euthanized shortly before the calculated farrowing date. Sows and piglets were grossly examined and necropsied. Organs (spleen, tonsil, lymph node, and kidney), EDTA-blood and serum were collected from all animals. All samples were tested for antibodies against CSFV glycoproteins E2 and E^rns as well as CSFV (virus, antigen and genome). It could be demonstrated that the vaccine complies with all requirements, i.e. no virus was found in the blood of vaccinated sows and their fetuses, and no antibodies were found in the serum of the fetuses from the vaccinated sows. All controls were valid.Thus, it was demonstrated that a single dose vaccination in the sows efficiently protected the offspring against transplacental infection with a moderately virulent CSFV strain.     

QS-21 structure/function studies: effect of acylation on adjuvant activity

QS-21 is a natural saponin adjuvant derived from the tree Quillaja saponaria Molina. Previous studies over a limited dose range suggested the acylation is critical to adjuvant activity. In this study, we prepared DS-1 (deacylated QS-21) and RDS-1 (reacylated DS-1 with dodecylamine at a different site than QS-21) to determine the effect on a dose-response curve over a wider range in mice. DS-1 and RDS-1 induced IgG1 responses at higher doses compared to that induced by QS-21. DS-1 was inactive for inducing IgG2a or CTL responses at any doses. RDS-1 showed moderate IgG2a response at 240 microg, but did not show CTL response at any dose evaluated.     

Effects of different adjuvants on rotavirus antibody responses and protection in mice following intramuscular immunization with inactivated rotavirus

I.m. immunization of mice with inactivated rotavirus particles protects against subsequent infection. To optimize protection, the effects of different adjuvants (QS-21, QS-7, QUIL A, PCPP and RAS) with potential for human use were compared. Twenty-eight days after i.m. immunization with 20 microg of purified, UV/psoralen-inactivated murine rotavirus (EDIM), either with or without adjuvant, BALB/c mice were orally challenged with live EDIM and virus shedding was measured. All five adjuvants stimulated large (P < 0.001) increases in rotavirus antibody, but significant differences were found between adjuvants. The order of rotavirus IgG responses, i.e. no adjuvant < RAS < QS-7 < Quil A < QS-21 < PCPP, was the same as the order of protection except that QS-21 and PCPP were reversed. These results establish the importance of adjuvants during i.m. immunization with rotavirus and identify those with the greatest potential.     

Immune response against grouper nervous necrosis virus by vaccination of virus-like particles

The grouper is a high-value fish in the seafood market. Grouper nervous necrosis virus (GNNV) causes mass mortality, near 100% in larvae and juveniles, which has great economic impact on the aquaculture of the marine fish. Since vaccination is one of the best methods against viral diseases, grouper Epinephelus lanceolatus was injected with virus-like particles (VLPs) of GNNV at different dosages and injection frequencies. The anti-sera of vaccinated fish were analyzed with antigen-capture ELISA to quantify immunization titer. The antibody titers in the vaccinated fish increased remarkably within 4 weeks, during which time the antibody was definitely capable to neutralize the native virus. With one shot of 10-250 microg VLPs, the stimulated antibody titer reached a steady saturation level in 1 month, among which the titers by one shot of 100 and 250 microg VLPs were 13% higher than by 10 microg. Two shots of 10 and 100 microg VLPs increased to maximum titer, which was 29% higher than one shot, whereas two shots of 250 microg VLPs and four shots of 100 microg VLPs dramatically downgraded the titers by -23% and -44%, respectively. These results imply that the overdose effects occurred in total dosages higher than 200 microg VLPs. The experiments of VLP vaccine with adjuvant revealed that the adjuvant is not required for increasing the efficacy of the VLP vaccine. Immunization with the VLPs can also stimulate fish to produce high antibody titer for more than 5 months, which can be correlated to long-term protection. When VLPs are used as vaccine agent, a dosage at 1 microg/g of fish body weight is enough to stimulate a full-scale immune response.     

Immunologic responses and adverse reactions to Freund's-adjuvanted porcine zona pellucida immuno-contraceptives in domestic cats

A vaccine of native PZP with Freund's adjuvant has been widely used in zoo and wild ungulates, but safety in felids has not been evaluated. General health, immune response, and ovarian histology were assessed in five domestic cats vaccinated with PZP-Freund's and five cats given Freund's adjuvant alone. Peak antibody titers occurred 3 weeks after the third vaccination, and no ovarian lesions were present 6 months after vaccination. Seven cats developed extensive granulomatous reactions at injection sites, lymph nodes, and multiple visceral organs including lungs and brain. Persistent hypercalcemia and compromised renal function occurred in three cats with elevated serum calcitriol of probable macrophage origin. One cat died from an injection site sarcoma. Because of these severe adverse reactions, Freund's adjuvant is contraindicated in cats, and other adjuvants for PZP vaccines should be tested in cats for adverse reactions before use.     

Assessment of the efficacy of an attenuated live marker classical swine fever vaccine (Flc-LOM-BErns) in pregnant sows

Here, we constructed an attenuated live marker classical swine fever (CSF) vaccine (Flc-LOM-BE^rns) to eradicate CSF. This was done by taking infectious clone Flc-LOM, which is based on an attenuated live CSF vaccine virus (LOM strain), and removing the full-length classical swine fever virus (CSFV) E^rns sequences and the 3′ end (52 base pairs) of the CSFV capsid. These regions were substituted with the full-length bovine viral diarrhoea virus (BVDV) E^rns gene sequence and the 3′ end (52 base pairs) of the BVDV capsid gene. Sows were vaccinated with the Flc-LOM-BE^rns vaccine 3 weeks before insemination and then challenged with virulent CSFV at the early, mid- or late stages of pregnancy. We then examined transplacental transmission to the foetuses. Piglets born to sows vaccinated with Flc-LOM-BE^rns did not show vertical infection, regardless of challenge time. In addition, CSFV challenge did not affect the delivery date, weight or length of the foetus. Pregnant sows inoculated with the Flc-LOM-BE^rns vaccine were anti-CSF E^rns antibody-negative and anti-BVDV E^rns antibody-positive. Challenge of pregnant sows with virulent CSFV resulted in anti-CSF E^rns antibody positivity. These results strongly indicate that differential diagnosis can be conducted between the Flc-LOM-BE^rns vaccinated animal and virulent CSFV affected animal by detecting antibody against BVDV E^rns or CSF E^rns gene. Therefore, the Flc-LOM-BE^rns vaccine may fulfil the function of differential diagnosis which required for DIVA vaccine.     

Effects of L-carnitine supplementation on milk production, litter gains and back-fat thickness in sows with a low energy and protein intake during lactation

The present study investigated the effect of L-carnitine supplementation during pregnancy (125 mg/d) and lactation (250 mg/d) on milk production, litter gains and back-fat thickness in sows fed a low-energy and low-protein diet during lactation. Sows supplemented with L-carnitine produced more milk on days 11 and 18 of lactation (+18 %; P<0.05) and had higher litter gains during suckling (+20 %; P<0.01) than control sows. Loss of body weight during lactation was similar in both groups, but sows supplemented with L-carnitine had a greater reduction of back-fat thickness (+45 %; P<0.05) during lactation than control sows. In conclusion, this study shows that L-carnitine increases milk production and litter gains in sows in a strongly negative energy and N balance, and enhances body fat mobilisation.     

Observations on experimental inactivated vaccines for contagious bovine pleuropneumonia

In two trials the efficacy of inactivated vaccines against contagious bovine pleuropneumonia was tested by exposing vaccinated cattle to droplet infection provided by close contact with experimentally infected 'donors'. Complete protection was given by an extreme form of vaccination in which a heavy suspension of killed Mycoplasma mycoides subsp. mycoides emulsified with Freund's complete adjuvant was given in two large doses. 'Mouse-protective antibody' (MPA) was also produced, i.e. serum transferred to mice 2-4 h before intraperitoneal challenge prevented the development of mycoplasmaemia. However, the study did not answer the question 'Is MPA protective for cattle?'. No protection was given by a milder form of vaccination in which a lighter suspension of killed mycoplasmas emulsified with Freund's incomplete adjuvant was given in a comparatively small dose on a single occasion.     

Effect of immunological adjuvant combinations on the antibody and T-cell response to vaccination with MUC1-KLH and GD3-KLH conjugates

A year ago we described a comparison of 19 immunological adjuvants for their ability to augment antibody and T-cell responses against vaccines containing two cancer antigens, GD3 ganglioside and MUC1 peptide, covalently attached to keyhole limpet hemocyanin (KLH). As in our previous experience, the saponin fraction QS-21 was the most potent single adjuvant but several other adjuvants also had potent adjuvant activity. Induction of an immune response against cancer antigens is generally difficult because these antigens are autoantigens. To get maximal benefit from the adjuvant component of cancer vaccines we have now tested whether combinations of the optimal adjuvants induced an improved immune response compared to QS-21 alone. Since over the intervening year a new semi-synthetic saponin adjuvant (GPI-0100) containing the dodecylamide derivative of hydrolyzed naturally-occurring saponins had become available, this was tested as well. Twelve different adjuvant combinations and GPI-0100 were compared for their ability to augment (1) antibody responses against GD3 and MUC1 and (2) T-cell responses against GD3, MUC1 and KLH. GPI-0100 and five adjuvant combinations were superior to QS-21 alone for induction of IgM and IgG antibodies against MUC1 and/or GD3: QS-21 plus bacterial nucleotide CpG, QS-21 plus monophosphoryl lipid A (MPL), QS-21 plus non-ionic block copolymer CRL-1005, QS-21 plus Titermax and Titermax plus CpG. Antibody responses were documented both by ELISA against purified antigens and by FACS for cell surface reactivity. There was no evidence for T-cell immunity against GD3 or MUC1. The antibody responses against GD3 and MUC1 were, however, strongly correlated with IFN-gamma release and DTH against KLH. These results demonstrate that combinations of immunological adjuvants are able to augment antibody and T-cell responses to these conjugates beyond that attainable with QS-21 alone, and again confirm the absolute necessity of potent adjuvants or adjuvant combinations for optimal immunogenicity with conjugate vaccines.     

Three double-blind, randomized trials evaluating the safety and tolerance of different formulations of the saponin adjuvant QS-21.

The effects of the adjuvant QS-21 in various formulations on immediate pain on injection after intramuscular injection were evaluated in three Phase I clinical trials in healthy adults. Each trial was designed as a double-blind, randomized, four-way or five-way cross-over study with each subject acting as his/her own control. In the first trial, four formulations designed to evaluate the effect of QS-21 or pH (over a range of 6--7.2) were evaluated: phosphate-buffered saline at pH 6.0 or 7.2, and 50 microg of QS-21 in phosphate-buffered saline at pH 6.0 or 7.2. Thirty-three volunteers received each of the four intramuscular injections in random order separated by approximately 1 week. The volunteers assessed the immediate injection pain from 0 to 10 (none to most pain). The data indicate that the presence of QS-21, but not pH, is associated with transient injection site pain. The second trial, which utilized the same design as the first trial, evaluated formulations of QS-21 in various excipients. Fifteen volunteers received phosphate-buffered saline, QS-21/PBS, QS-21/aluminum hydroxide, and QS-21/4 mg/ml of polysorbate 80. Polysorbate 80, but not aluminum hydroxide, reduced the mean pain score compared to QS-21/PBS. The third trial evaluated formulations of QS-21 in additional excipients. Fifteen volunteers received aluminum hydroxide (without QS-21), QS-21/PBS, QS-21/0.72% benzyl alcohol, QS-21/30 mg/ml of hydroxypropyl-beta-cyclodextrin, and QS-21/8-mg/ml of polysorbate 80. Benzyl alcohol, cyclodextrin, and the higher concentration of polysorbate 80 reduced the pain scores associated with QS-21. Hence, QS-21 is associated with injection pain in simple buffer formulations, but it is possible to improve the acceptability of QS-21-containing formulations through reformulation with certain excipients.     

Red blood cell-mediated delivery of recombinant HIV-1 Tat protein in mice induces anti-Tat neutralizing antibodies and CTL

The immunotherapeutic potential of biologically active HIV-1 Tat protein coupled to autologous red blood cells (RBCs) was evaluated in a mouse model. HIV-1 Tat expressed in Escherichia coli and purified to homogeneity was found to be active in viral trans activation and efficiently internalised by monocyte-derived dendritic cells (MDDCs). The product of HIV-Tat biotinylation and coupling to RBCs by means of a biotin-avidin-biotin bridge, (RBC-Tat), showed no trans activation activity and was still efficiently internalized by MDDCs as compared to uncoupled Tat.Balb/c mice were then immunized with 10 microg of soluble Tat in complete Freund's adjuvant or with 40 ng of Tat coupled on RBCs surface and boosted at week 3, 6 and 25 with 5 microg soluble Tat in incomplete Freund's adjuvant or with 20 ng of RBC-coupled Tat, respectively. Anti-Tat antibody response was similar in both groups; however, 2/6 animals immunized with soluble Tat and 6/6 animals immunized with RBC-Tat developed anti-Tat neutralizing antibodies. In addition, at week 28 cytolytic anti-Tat CTLs were detected in all animals although they were slightly higher in mice immunized with RBC-Tat. These results indicate that RBC-mediated delivery of HIV-1 Tat, in amounts 250 times lower than soluble Tat, is safe and induces specific CTL responses and neutralizing antibodies.     

Heterotypic protection from rotavirus infection in mice vaccinated with virus-like particles

Virus-like particles (VLPs) composed of rotavirus VP2, VP6, and VP7 of G1 or G3 serotype specificity were produced in insect cells coinfected with recombinant baculoviruses expressing single rotavirus genes. The VLPs were purified and subsequently evaluated for immunogenicity and protection in the adult mouse model of rotavirus infection. Mice were vaccinated twice intramuscularly with G1 VLPs formulated with Quillaja saponaria (QS-21) or adsorbed to aluminium hydroxide (AlOH), or with G1 VLPs alone. G3 VLPs, G1 plus G3 VLPs, inactivated SA11 virions formulated with QS-21, or adjuvants were similarly inoculated as controls. Mice were examined for serum and fecal antibody responses by ELISA or microneutralization assays. Protective efficacy of the VLP vaccine formulations against oral challenge with the G3 murine ECwt rotavirus was assessed by comparing the antigen shed in stool of the VLP-vaccinated mice to that of the adjuvant-immunized mice. G1 VLPs in QS-21 induced significantly higher serum and intestinal antibody titers than G1 VLPs in AlOH or G1 VLPs alone. QS-21 also heightened serum and fecal antibody responses to G3 VLPs. These QS-21-augmented antibody responses were further characterized by equivalent IgG1 and IgG2a titers in sera, suggesting that G1 or G3 VLPs in QS-21 induced a balanced Th1/Th2 response. G1 VLPs in QS-21 induced partial protection (88%) against oral challenge with the heterotypic ECwt virus, whereas G3 VLPs in QS-21 induced complete protection (100%). In contrast, G1 VLPs when formulated with AlOH induced a predominant Th2 response and did not protect (1%) mice from virus challenge. Our results indicate that the type of adjuvant used clearly influences both antibody responses to rotavirus VLPs and the protective efficacy against rotavirus infections. These data have important implications for the development of parenteral vaccines to ameliorate rotavirus disease.     

The effect of vaccination regimen on the transfer of foot and mouth disease antibodies from the sow to her piglets.

Four groups of pregnant sows were inoculated with type O1 foot and mouth disease (FMD) oil emulsion vaccine at various times before farrowing and samples of the sow''s serum, colostrum and milk, and piglet''s serum, collected during the first week after farrowing, were analysed for FMD virus neutralizing activity. No FMD neutralizing antibodies were detectable in the piglets serum at birth but they were present 1.5 h after suckling and peak titres were reached 1-3 days later. There was no significant difference between the antibody titres of colostrum samples collected from different teats at farrowing. However, similar samples collected 3 days later showed significant (P less than 0.005) fore to hind variation. The principal FMD virus neutralizing antibody class present in the sow''s serum at farrowing and in their 3-day-old piglets was governed by the inoculation schedule employed. When the last vaccinations were given congruent to 30 days before farrowing (dbf) the predominant FMD virus neutralizing class was IgG. However, when the sows were vaccinated only congruent to 12 dbf the predominant class was IgM. A significant correlation was observed between the sow''s serum titres and colostrum titres at farrowing (r = 0.90), and also between sows colostrum titres at farrowing and their 3-day-old piglets serum titres (r = 0.99).     

Vaccination against Schistosoma mansoni infection using 74 kDa Schistosoma protein antigen.

An IgG2a anti-Schistosoma mansoni mouse monoclonal antibody was shown to passively protect Swiss mice. The 74 kDa target antigen was isolated from antigenic extracts of S. mansoni adult worms. Swiss and C57 BL/6J mice were immunized with 30, 50, 100 and 200 microg antigen/mouse doses with and without Freund's adjuvant. Sera of immunized mice showed high reactivity against 74 kDa antigen. The highest protection level (76.6% in Swiss mice and 50.1% in C57 BL/6J mice) was obtained using the 50 microg antigen dose with and without Freund's adjuvant. A marked reduction in granuloma number and intensity of collagen and reticular granuloma fibers was observed. The 74 kDa antigen has the ability to protect mice of different strains and to modulate the host immune system.