Bartha-k61 vaccine protects growing pigs against challenge with an emerging variant pseudorabies virus

Since late 2011, pseudorabies (PR) has resurfaced in many large pig farms, causing great economic loss for the swine industry in China. The PRV variant strain with high virulence and antigenic variation has been considered to be the main cause, and much attention has been focused on how to prevent and control the reoccurrence of this disease in China. In this study, two kinds of vaccination strategy were employed to evaluate the protective effects of Bartha-k61vaccine against both variant PRV (XJ5) and classical PRV (Ra) strain challenge. Humoral immunity response, clinical signs, survival rate, body weight, virus shedding and pathology were assessed in commercial pigs. The results showed that Bartha-k61vaccine, administered either once or twice, was effective against the PRV variant (XJ5) challenge, while no significant differences were observed between single and prime-boost vaccinated pigs. However, pigs vaccinated twice had better body weight gains than those vaccinated once, following challenge with the classical PRV strain (Ra) (p < 0.01). Therefore, the Bartha-k61 vaccine appears to be an effective vaccine to control the spread of PRV variants in China in the absence of new powerful candidate vaccines specific to these PRV strains.     

Pseudorabies Virus Variant in Bartha-K61–Vaccinated Pigs,China, 2012

The widely used pseudorabies virus (PRV) Bartha-K61 vaccine has played a key role in the eradication of PRV. Since late 2011, however, a disease characterized by neurologic symptoms and a high number of deaths among newborn piglets has occurred among Bartha-K61–vaccinated pigs on many farms in China. Clinical samples from pigs on 15 farms in 6 provinces were examined. The PRV gE gene was detectable by PCR in all samples, and sequence analysis of the gE gene showed that all isolates belonged to a relatively independent cluster and contained 2 amino acid insertions. A PRV (named HeN1) was isolated and caused transitional fever in pigs. In protection assays, Bartha-K61 vaccine provided 100% protection against lethal challenge with SC (a classical PRV) but only 50% protection against 4 challenges with strain HeN1. The findings suggest that Bartha-K61 vaccine does not provide effective protection against PRV HeN1 infection.     

Novel pseudorabies virus variant with defects in TK,gE and gI protects growing pigs against lethal challenge

One of the distinct features of the emerging Chinese pseudorabies virus (PRV) variant is its ability to cause severe neurological signs and high mortality in growing pigs in Bartha-K61-vaccinated pig farms. Either single- or multiple-gene-deleted live vaccine candidates have been developed; however, none was evaluated thoroughly in growing pigs. Here, we generated rSMXΔgI/gEΔTK, an attenuated PRV variant with defects in TK, gI and gE genes. The growth kinetics of the attenuated virus was similar to the wild type (wt) strain. It was safe for 1-day-old piglets. Twenty one-day-old weaned pigs were immunized intramuscularly either with 10^6.0 TCID₅₀ of rSMXΔgI/gEΔTK or one dose of commercial Bartha-K61 vaccine, or with DMEM, and were challenged intranasally with 10^7.0 TCID₅₀ wt virus at 28 days post vaccination. rSMXΔgI/gEΔTK elicited higher level neutralization antibody against both PRV variant SMX and Bartha-K61 strain, while Bartha-K61 vaccine elicited lower neutralization activity of antibody against SMX. After challenge, all pigs in rSMXΔgI/gEΔTK group survived without any clinical signs, while unvaccinated group showed 100% mortality, and Bartha-K61 group showed severe respiratory symptoms and 3 out of 5 pigs exhibited severe neurological signs. Pigs in rSMXΔgI/gEΔTK group gained significantly higher body weight and diminished viral excretion titer and period, compared with Bartha-K61 group. Furthermore, the safety and efficacy of rSMXΔgI/gEΔTK was also evaluated in sheep and compared with local vaccine in growing pigs. These data suggest that the attenuated strain rSMXΔgI/gEΔTK is a promising live marker vaccine candidate for PR control in the context of emerging PRV variants.     

Efficacy of the oral rabies virus vaccine strain SPBN GASGAS in foxes and raccoon dogs

To test the immunogenicity and efficacy of a new oral rabies virus vaccine strain SPBN GASGAS in wildlife target species, one group of foxes and two groups of raccoon dogs were offered a bait containing 1.7 ml of the vaccine (10^6.6 FFU/ml; 10^6.8 FFU/dose) and subsequently challenged approximately 180 days later with a fox rabies virus isolate. One group of raccoon dogs (n = 30) received the same challenge dose (10^0.7 MICLD₅₀/ml) as the red foxes (n = 29). The other group with raccoon dogs (n = 28) together with 8 animals that received the vaccine dose by direct instillation into the oral cavity (DIOC) were infected with a 40-fold higher dose of the challenge virus (10^2.3 MICLD₅₀/ml). All but one of the 29 vaccinated foxes survived the challenge infection; meanwhile all 12 control foxes succumbed to rabies. Twenty-eight of 30 vaccinated raccoon dogs challenged with the same dose survived the infection, however only six of 12 control animals succumbed. When the higher challenge dose was administered, all 12 control animals died from rabies and all 36 vaccinated animals (28 baited plus 8 DIOC) survived. Blood samples were collected at different time points post vaccination and examined by both RFFIT and ELISA. The kinetics of the measured immune response was similar for both species, although in RFFIT slightly higher values were observed in foxes than in raccoon dogs. However, the immune response as measured in ELISA was identical for both species. The oral rabies virus vaccine SPBN GASGAS meets the efficacy requirements for live rabies virus vaccines as laid down by the European Pharmacopoeia.     

A effective DNA vaccine against diverse genotype J infectious hematopoietic necrosis virus strains prevalent in China

Infectious hematopoietic necrosis virus (IHNV) is the most important pathogen threatening the aquaculture of salmonid fish in China. In this study, a DNA vaccine, designated pIHNch-G, was constructed with the glycoprotein (G) gene of a Chinese IHNV isolate SD-12 (also called Sn1203) of genotype J. The minimal dose of vaccine required, the expression of the Mx-1 gene in the muscle (vaccine delivery site) and anterior kidney, and the titers of the neutralizing antibodies produced were used to evaluate the vaccine efficacy. To assess the potential utility of the vaccine in controlling IHNV throughout China, the cross protective efficacy of the vaccine was determined by challenging fish with a broad range of IHNV strains from different geographic locations in China. A single 100 ng dose of the vaccine conferred almost full protection to rainbow trout fry (3 g) against waterborne or intraperitoneal injection challenge with IHNV strain SD-12 as early as 4 days post-vaccination (d.p.v.), and significant protection was still observed at 180 d.p.v. Intragenogroup challenges showed that the DNA vaccine provided similar protection to the fish against all the Chinese IHNV isolates tested, suggesting that the vaccine can be widely used in China. Mx-1 gene expression was significantly upregulated in the muscle tissue (vaccine delivery site) and anterior kidney in the vaccinated rainbow trout at both 4 and 7 d.p.v. Similar levels of neutralizing antibodies were determined with each of the Chinese IHNV strains at 60 and 180 d.p.v. This DNA vaccine should play an important role in the control of IHN in China.     

Evaluation of the attenuation,immunogenicity, and efficacy of a live virus vaccine generated by codon-pair bias de-optimization of the 2009 pandemic H1N1 influenza virus,in ferrets

Codon-pair bias de-optimization (CPBD) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. Previously, this technology has been used to attenuate the influenza A/Puerto Rico/8/34 (H1N1) virus. The de-optimized virus was immunogenic and protected inbred mice from challenge. In order to assess whether CPBD could be used to produce a live vaccine against a clinically relevant influenza virus, we generated an influenza A/California/07/2009 pandemic H1N1 (2009 pH1N1) virus with de-optimized HA and NA gene segments (2009 pH1N1-(HA + NA)^Min), and evaluated viral replication and protein expression in MDCK cells, and attenuation, immunogenicity, and efficacy in outbred ferrets. The 2009 pH1N1-(HA + NA)^Min virus grew to a similar titer as the 2009 pH1N1 wild type (wt) virus in MDCK cells (∼10⁶ TCID₅₀/ml), despite reduced HA and NA protein expression on western blot. In ferrets, intranasal inoculation of 2009 pH1N1-(HA + NA)^Min virus at doses ranging from 10³ to 10⁵ TCID₅₀ led to seroconversion in all animals and protection from challenge with the 2009 pH1N1 wt virus 28 days later. The 2009 pH1N1-(HA + NA)^Min virus did not cause clinical illness in ferrets, but replicated to a similar titer as the wt virus in the upper and lower respiratory tract, suggesting that de-optimization of additional gene segments may be warranted for improved attenuation. Taken together, our data demonstrate the potential of using CPBD technology for the development of a live influenza virus vaccine if the level of attenuation is optimized.     

Antigenic variation of LaSota and genotype VII Newcastle disease virus (NDV) and their efficacy against challenge with velogenic NDV

Continued monitoring and evaluation of vaccine efficacy against prevalent or newly isolated strains has great importance in advising Newcastle disease (ND) immunization strategy. In this study, we systematically analysed the antigenic variation between genotype VII NDV aSG10 and the commercial vaccine strain LaSota, and assessed their efficacy against challenge with velogenic NDV by serological analysis and animal testing. We show that these two viruses are antigenically distinguishable; anti-NDV aSG10 hyper-immune sera demonstrated higher haemagglutination inhibition (HI) titres (11.13 ± 0.30log₂) against the aSG10 virus, compared with titres against LaSota (9.53 ± 0.50log₂). Conversely, the hyper-immune sera from LaSota showed higher HI titres against LaSota virus (9.73 ± 0.36log₂), but 2-fold lower HI titre against aSG10 (8.87 ± 0.38log₂). Each serum neutralised heterologous virus, but neutralisation titres were always 3- to 6-fold higher against its homologous strain than heterologous virus. The cross-reactivity R value between aSG10 and LaSota was 0.23, indicating that they are loosely related with major antigenic differences within a single serotype. The results of animal tests revealed that the aSG10 vaccine had a significantly higher protection rate than the LaSota vaccine against genotype VII NDV, regardless of intramuscular (IM) or eye drop/intranasal (ED/IN) route of SG10 challenge. Compared with IM administration, chicken flocks needed higher HI antibody levels to obtain sufficient protection when challenged by the natural ED/IN route. These results are highly informative for better control of ND in the poultry industry.     

Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge

The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0 × 10⁸ to 2.1 × 10¹¹ particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R² = 0.97) and viremia (R² = 0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R² = 0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge.     

Simultaneous subcutaneous and conjunctival administration of the influenza viral vector based Brucella abortus vaccine to pregnant heifers provides better protection against B. abortus 544 infection than the commercial B. abortus S19 vaccine

In this study, we explored possibility of increasing the protective efficacy of our novel influenza viral vector based B. abortus vaccine (Flu-BA) in pregnant heifers by adapting an innovative method of vaccine delivery. We administered the vaccine concurrently via the conjunctival and subcutaneous routes to pregnant heifers, and these routes were previously tested individually. The Flu-BA vaccination of pregnant heifers (n = 9) against a challenge B. abortus 544 infection provided protection from abortion, infection of heifers and fetuses/calves by 88.8%, 100% and 100%, respectively (alpha = 0.004–0.0007 vs. negative control; n = 7). Our candidate vaccine using this delivery method provided slightly better protection than the commercial B. abortus S19 vaccine in pregnant heifers (n = 8), which provided protection from abortion, infection of heifers and fetuses/calves by 87.5%, 75% and 87.5%, respectively. This improved method of the Flu-BA vaccine administration is highly recommended for the recovery of farms which has high prevalence of brucellosis.     

Recombinant CP40 from Corynebacterium pseudotuberculosis confers protection in mice after challenge with a virulent strain

BackgroundCaseous Lymphadenitis (CLA) is a contagious, infectious, chronic disease caused by Corynebacterium pseudotuberculosis, which affects mainly sheep and goats. The clinical prevalence of CLA in Brazil is 30%, resulting in decreased milk production, weight loss, and unusable meat and leather. Prophylaxis is based on vaccination; however, current vaccinations do not offer effective protection against the infection, which makes the development of a new vaccine essential to control this disease.Experimental approachHere, we developed a recombinant vaccine based on CP40 protein (rCP40) combined with an adjuvant (Freund's complete adjuvant or saponin) and evaluated its efficacy in a murine model of CLA. Female BALB/c mice were used in an immunization assay.Key resultsrCP40 induced high levels of IgG2a and IgG2b antibodies. After challenge with a virulent strain of C. pseudotuberculosis C57 (10⁴ CFU/mL), the levels of IgG2a and IgG2b were sustained, indicating a Th1 response. The groups immunized with rCP40 protein (GES and GEF groups) showed 100% protection and was statistically significant in the GES and GEF groups (p < 0.037 and p < 0.0952, respectively).ConclusionsThe results indicated the recombinant protein CP40 induced an specific immune response in mice that was able to afford protection after challenge, regardless the adjuvant used in the formulation.     

Characterization of a moderately pathogenic pseudorabies virus variant isolated in China, 2014

In this study, we reported a moderately pathogenic pseudorabies virus (PRV) variant isolated from one Bartha-K61-vaccinated pig farm in Weifang, Shandong Province, China, 2014. The sick piglets in the farm were characterized by anorexia, weight loss and neurologic symptoms but did not die. Sequence alignment of the gE gene indicated that it belonged to a new mutated PRV strain and about 15% amino acid sites had mutations, deficiencies and insertions compared to the other PRV strains. The gD gene had two amino acid insertions and ten amino acid mutations in comparison with the Bartha-K61 vaccine strain. The TK and gM genes were the same as one highly pathogenic PRV TJ strain. Evidence from virus isolation, laboratory challenge, serological detection and histopathologic examination confirmed that the etiological agent of the disease is PRV SD1404, which is a moderately pathogenic strain and causes piglets to be sick but not to die. PRV SD1404 strain is different from other reports and should be paid more attention to avoid economic losses.     

An influenza viral vector Brucella abortus vaccine induces good cross-protection against Brucella melitensis infection in pregnant heifers

Brucella melitensis can be transmitted and cause disease in cattle herds as a result of inadequate management of mixed livestock farms. Ideally, vaccines against Brucella abortus for cattle should also provide cross-protection against B. melitensis. Previously we created a novel influenza viral vector B. abortus (Flu-BA) vaccine expressing the Brucella ribosomal proteins L7/L12 or Omp16. This study demonstrated Flu-BA vaccine with adjuvant Montanide Gel01 provided 100% protection against abortion in vaccinated pregnant heifers and good cross-protection of the heifers and their calves or fetuses (90–100%) after challenge with B. melitensis 16 M; the level of protection provided by Flu-BA was comparable to the commercial vaccine B. abortus S19. In terms of the index of infection and colonization of Brucella in tissues, both vaccines demonstrated significant (P = 0.02 to P < 0.0001) protection against B. melitensis 16 M infection compared to the negative control group (PBS + Montanide Gel01). Thus, we conclude the Flu-BA vaccine provides cross-protection against B. melitensis infection in pregnant heifers.     

A native outer membrane vesicle vaccine confers protection against meningococcal colonization in human CEACAM1 transgenic mice

BackgroundThe effect of protein-based meningococcal vaccines on prevention of nasopharyngeal colonization has been difficult to investigate experimentally because a reliable animal colonization model did not exist.MethodsHuman CEACAM1 transgenic mice, which can be colonized by meningococci, were immunized IP with one of two meningococcal native outer membrane vesicle (NOMV) vaccines prepared from mutants with attenuated endotoxin (lpxL1 knockout) and over-expressed sub-family B Factor H-binding proteins (FHbp). Animals were challenged intranasally two weeks after the third dose with wild-type strain H44/76, or were treated IP with anti-NOMV serum before and during the bacterial challenge.ResultsThe NOMV-1 vaccine, prepared from the serogroup B H44/76 mutant, elicited ∼40-fold higher serum bactericidal antibody titers against the wild-type H44/76 challenge strain than the NOMV-2 vaccine prepared from a heterologous serogroup W mutant strain with different PorA and FHbp amino acid sequence variants. Compared to aluminum hydroxide-immunized control mice, the efficacy for prevention of any H44/76 colonization was 93% (95% confidence interval, 52–99, P < 0.0001) for the NOMV-1 vaccine, and 19% (−3–36, P = 0.23) for NOMV-2. NOMV-2-vaccinated mice had a 5.6-fold decrease in geometric mean CFU of bacteria per animal in tracheal washes compared to control mice (P = 0.007). The efficacy of passive administration of serum from NOMV-1-vaccinated mice to immunologically naïve mice against colonization was 44% (17–61; P = 0.002).ConclusionsBoth NOMV vaccines protected against meningococcal colonization but there was greater protection by the NOMV-1 vaccine with antigens matched with the challenge strain. Meningococcal vaccines that target protein antigens have potential to decrease colonization.     

Regulated expression of virulence gene mviN provides protective immunity and colonization control of Salmonella in poultry

Current live attenuated vaccines for control of Salmonella in poultry persist in the ceca and may persist in the environment. In this paper we report the construction and characterization of the vaccine efficacy of a Salmonella mutant strain with inducible mviN expression and rapid clearance from the host. The mutant was effective in oral immunization of the broiler chicken host against a virulent Salmonella oral challenge strain, having a mean 7 × 10⁶ CFU/g in the ceca of unvaccinated controls compared to a mean 2 × 10³ CFU/g in the ceca of vaccinated chickens at 4 weeks post-challenge (6 weeks of age). The mutant strain also demonstrated immunogenicity, reduced organ colonization, and rapid clearance in broiler chickens within 3 weeks of inoculation.     

Adjuvant potential of resiquimod with inactivated Newcastle disease vaccine and its mechanism of action in chicken

Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10 birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log₂ HI titre of 6.4 ± 0.16 and 6.8 ± 0.13, respectively. The response was significantly higher than that of group B or C (P < 0.01). LTT stimulation index (P ≤ 0.01) as well as CD4⁺ and CD8⁺ cells in flow cytometry (P < 0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P < 0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes.     

Vaccination with a live attenuated Acinetobacter baumannii deficient in thioredoxin provides protection against systemic Acinetobacter infection

Multi-drug resistant Acinetobacter baumannii (MDR-Ab), an opportunistic pathogen associated with nosocomial and combat related infections, has a high mortality due to its virulence and limited treatment options. Deletion of the thioredoxin gene (TrxA) from a clinical isolate of MDR-Ab resulted in a 100-fold increase in 50% lethal dose (LD₅₀) in a systemic challenge murine model. Thus, we investigated the potential use of this attenuated strain as a live vaccine against MDR-Ab. Mice were vaccinated by subcutaneous (s.c.) injection of 2 × 10⁵ CFU of the ΔtrxA mutant, boosted 14 days later with an equivalent inoculum, and then challenged 30 days post-vaccination by i.p. injection with 10 LD₅₀ of the wild type (WT) Ci79 strain. Efficacy of vaccination was evaluated by monitoring MDR-Ab specific antibody titers and cytokine production, observing pathology and organ burdens after WT challenge, and measuring levels of serum pentraxin-3, a molecular correlate of A. baumannii infection severity, before and after challenge. Mice vaccinated with ΔtrxA were fully protected against the lethal challenge of WT. However, minimal immunoglobulin class switching was observed with IgM predominating. Spleens harvested from vaccinated mice exhibited negligible levels of IL-4, IFN-γ and IL-17 production when stimulated with UV-inactivated WT Ci79. Importantly, tissues obtained from vaccinated mice displayed reduced pathology and organ burden compared to challenged non-vaccinated mice. Additionally, serum pentraxin-3 concentrations were not increased 24 h after challenge in vaccinated mice, correlating with reduction of WT MDR-Ab infection in ΔtrxA immunized mice. Furthermore, passive immunization with ΔtrxA-immune sera provided protection against lethal systemic Ci79 challenge. Collectively, the defined live attenuated ΔtrxA strain is a vaccine candidate against emerging MDR Acinetobacter infection.     

Lasting immune memory against hepatitis B following challenge 10–11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11–12 months of age

BackgroundThe combined hexavalent diphtheria–tetanus–pertussis–hepatitis B-inactivated poliomyelitis – Haemophilus influenzae type b conjugate vaccine (Infanrix hexa™; DTPa-HBV-IPV/Hib: GlaxoSmithKline Vaccines) induces robust responses to the HBV component when administered at 3, 5 and 11–12 months of age. We assessed long term HBV antibody persistence 10–11 years after primary vaccination in infancy.MethodsAntibody persistence and immune memory were assessed post-primary vaccination at 3, 5, 11–12 months with DTPa-HBV-IPV/Hib, or monovalent HBV vaccine (Engerix™ B, GlaxoSmithKline Vaccines) co-administered with DTPa-IPV/Hib (Infanrix™-IPV/Hib, GlaxoSmithKline Vaccines) in 185 children aged 11–12 years. Blood samples were collected before and 1 month after a challenge dose of Engerix™ B (10 μg dose).Results10–11 years after primary vaccination the percentage of subjects with persisting anti-HBs antibody concentrations ≥10 mIU/ml was 48.4% in the DTPa-HBV-IPV/Hib group and 58.4% in the DTPa-IPV/Hib + HBV group. After the HBV challenge dose, the percentage with anti-HBs ≥100 mIU/ml increased from 14.7% to 93.6% in the DTPa-HBV-IPV/Hib group and 19.1% to 94.4% in the DTPa-IPV/Hib + HBV group. Anti-HBs GMCs increased by at least 187-fold in each group. An anamnestic response (≥4-fold increase in initially seropositive or anti-HBs concentration ≥10 mIU/ml in initially seronegative subjects) was observed in 96.8% and 96.6% of subjects in the DTPa-HBV-IPV/Hib and DTPa-IPV/Hib + HBV groups, respectively. No serious adverse events occurred that were considered related to challenge vaccination.ConclusionAdministration of HBV as part of a combination vaccine or as a monovalent vaccine induced long lasting immune memory against HBV in children primed at 3, 5 and 11 months of age. Antibody persistence and immune memory were similar, suggesting that protection afforded by DTPa-HBV-IPV/Hib and monovalent HBV vaccines, is likely to be of similar duration. The administration of HBV challenge dose 10–11 years after the 3, 5, 11–12 months primary schedule induced strong anamnestic responses and was well tolerated.This study is registered at www.clinicaltrials.gov NCT01138098.     

Protective effects of high-potency FMDV O1 Manisa monovalent vaccine in cattle challenged with FMDV O/SKR/2010 at 7 or 4 days post vaccination

Serotype O foot-and-mouth disease (FMD) virus belonging to the SEA topotype continues to be a significant problem in the Eastern Asia region, with outbreaks in Japan and South Korea resulting in the culling of over 3.5 million cattle and pigs in recent years. High-potency O1 Manisa vaccine was previously shown to provide protection in cattle 21 days post vaccination (dpv) following challenge with a representative virus, O/SKR/2010. This study tested the ability of the O1 Manisa vaccine to protect cattle from infection and disease with the O/SKR/2010 virus within just 4 or 7 days post vaccination. The vaccine protected 50% of cattle from clinical disease when administered 7 days prior to challenge, but was not protective with just 4 days between vaccination and challenge. Viraemia was significantly reduced in animals challenged 7 dpv but not 4 dpv, compared to unvaccinated controls, however, there were no effects on the level of virus detected in nasal and oral secretions regardless of vaccination time. The level of neutralising antibodies detected in cattle challenged 7 dpv correlated with protection from clinical disease. All animals seroconverted to FMDV non-structural proteins, suggesting no sterile protection. An equal number of animals became persistently infected in both vaccine groups. The results indicated that high-potency O1 Manisa vaccine administered just 7 days prior to challenge should provide partial protection of cattle if an outbreak of O/SKR/2010, or related viruses, occurs, and would be useful to limit spread of FMDV when used in conjunction with other control measures.