Efficiency of inactivated vaccines against heartwater in Burkina Faso: Impact of Ehrlichia ruminantium genetic diversity

In order to identify the appropriate strains to use in vaccination trials against heartwater in Burkina Faso, the protective effect of Gardel and Welgevonden strains was assessed against local strains on sheep vaccinated by infection-and-treatment method: Gardel protected significantly against Burkina Faso strains tested (survival rate 59% for immunised sheep vs 13% for control sheep) while Welgevonden did not (survival rate 45% for immunised sheep vs 25% for control sheep). The efficacy of the ISA50 inactivated vaccine, produced under industrial process, was evaluated in sheep during field challenges in two successive years. During year 1, there was a limited protective effect of the Gardel vaccine with 65% of survival rate for the vaccinated group compared to 49% for the control group (N = 153, p = 0.053). During year 2, the vaccine containing Gardel and a local strain gave an increased protective effect compared to the first trial: 72% of the vaccinated animals survived compared to 47% of the naïve animals (N = 173, p < 0.001). There was an important genetic diversity of strains in the field with detection of 11 different map1 genotypes in brains from control and vaccinated sheep post mortem. Map1 genotyping of strains detected in brains from control sheep showed that genotype distribution varied according to time and study areas, which could explain the difference in efficacy of the vaccine.     

First data on Eurasian wild boar response to oral immunization with BCG and challenge with a Mycobacterium bovis field strain

The Eurasian wild boar (Sus scrofa) is considered a reservoir for bovine tuberculosis (bTB) caused by Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex in south-central Spain. The vaccination of wildlife with BCG offers an alternative to culling and to movement restriction for the control of bTB among wildlife reservoirs. In this study, we hypothesized that oral BCG immunization of wild boar would affect the expression of immunoregulatory genes and confer protection against M. bovis. Three groups were used to describe the infection, pathological findings and gene expression profiles in wild boar: BCG-vaccinated and M. bovis-challenged (vaccinated challenged group; N = 6), non-vaccinated and M. bovis-challenged (non-vaccinated challenged group; N = 4), and non-vaccinated and mock-infected (control group; N = 2) animals. M. bovis was isolated from 50% (3/6) and 75% (3/4) of vaccinated challenged and non-vaccinated challenged animals, respectively. All four wild boar from the non-vaccinated challenged group developed bTB-compatible lesions 114 days after challenge. In contrast, only 50% of vaccinated challenged wild boar developed lesions. The PBMC mRNA levels of IL4, RANTES, C3, IFN-gamma and methylmalonyl-CoA mutase (MUT) were analyzed at several days post-vaccination (dpi). When vaccinated challenged animals were compared to controls, all five genes were significantly upregulated at the time of M. bovis infection at 186 dpi but IFN-gamma levels were also upregulated at 11 and 46 dpi. The C3 and MUT mRNA levels were higher at 46 dpi, and 11 and 186 dpi, respectively, in vaccinated protected wild boar when compared to non-vaccinated challenged animals. At the end of the experiment (300 dpi), the mRNA levels of selected genes were lower in non-vaccinated challenged animals when compared to control wild boar. Exposing wild boar to a dose of 10⁴ cfu of M. bovis by the oropharyngeal route is an adequate protocol to produce an infection model in this species. Our results suggested that oral BCG immunization of wild boar results in the upregulation of immunoregulatory genes that may be associated with protective response to M. bovis infection in this species. More studies on vaccine efficacy, delivery, and safety will be needed to confirm if oral vaccination with BCG could be used in bTB control programs for reducing M. bovis infection and clinical disease in wild boar.     

Transmission of mumps virus from mumps-vaccinated individuals to close contacts

During a recent mumps epidemic in the Netherlands caused by a genotype D mumps virus strain, we investigated the potential of vaccinated people to spread mumps disease to close contacts. We compared mumps viral titers of oral fluid specimens obtained by quantitative PCR from vaccinated (n = 60) and unvaccinated (n = 111) mumps patients. We also investigated the occurrence of mumps infection among the household contacts of vaccinated mumps patients. We found that viral titers are higher for unvaccinated patients than for vaccinated patients during the 1st 3 days after onset of disease. While no symptomatic cases were reported among the household contacts (n = 164) of vaccinated mumps patients (n = 36), there were cases with serological evidence of asymptomatic infection among vaccinated household contacts (9 of 66 vaccinated siblings). For two of these siblings, the vaccinated index patient was the most probable source of infection. We conclude that, in this particular outbreak, the risk of a close contact becoming infected by vaccinated patients was small, but present.     

Comparative varicella vaccine effectiveness during outbreaks in day-care centres

Background

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).

Methods

Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age < 11 months, vaccinated at age < 11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).

Findings

Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57–81, p < 0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix^® (RR = 2.8, 95%CI 1.0–7.8, p = 0.05) or Priorix-Tetra^® (RR = 2.4, 95%CI 0.7–8.3, p = 0.18) but lower for 2 doses of Priorix-Tetra^® (RR = 0.5, 95%CI 0.1–2.7, p = 0.41) than for 1 dose of Varivax^®.

Interpretation

Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.     

A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens

We studied the time course of serum IgG antibodies against 3 different pertussis vaccine antigens: PT (pertussis toxin), FHA (filamentous hemagglutinin), Prn (pertactin) in sera from individuals vaccinated with four different pertussis vaccines at 4 years of age: (N = 44, 44, 23 and 23, respectively,) and compared the responses to/after natural infection with Bordetella pertussis (N = 44, age 1–8 years).     

Sero-prevalence of mumps antibodies in subpopulations subsequently affected by a large scale mumps epidemic in Israel

Background and aims

Despite the high national vaccination coverage, a large outbreak of mumps occurred in Israel, in 2009-2010, with onset and heavy transmission in ultraorthodox Jewish communities and further country-wide spread. We examined the sero-prevalence of mumps antibodies in the subpopulations subsequently affected by this large mumps outbreak, compared with the general population.

Methods

The study was conducted in ultraorthodox Jewish communities, in Jerusalem district (N = 251), in Bnei Brak city in Tel Aviv district (N = 453), and in the general population (N = 1846), using residual sera of 1-20 year old subjects. Mumps IgG antibodies were measured using Enzygnost anti-parotitis virus IgG ELISA kit.

Results

Mumps sero-positivity was significantly lower in Jerusalem: 51.8% (95% CI 51.9-61.0), and Bnei Brak: 56.5% (95% CI 45.6-57.9), than in the general population: 68.1% (95% CI 66.0-70.2). Sero-positivity increased with age, however in Jerusalem it was substantially low (46%) in the age group 10-20 years. This age group comprised a significant portion of mumps patients in the 2009-2010 outbreak.

Conclusions

Low immunity levels, combined with overcrowding and social mixing, were the main predisposing factors of the enhanced epidemic transmission of mumps in the ultraorthodox Jewish communities and further country-wide spread.     

Molecular characterization of SG33 and Borghi vaccines used against myxomatosis

Myxoma virus is a poxvirus responsible for myxomatosis in European Rabbits (Oryctolagus cuniculus). The entire genome of the myxoma virus has been sequenced, allowing a systemic survey of the functions of a large number of putative pathogenic factors that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts. In Italy, industrial rabbits are mostly vaccinated against myxomatosis using the attenuated myxoma virus strains Borghi or SG33. We have identified genetic markers specific for Borghi or SG33 vaccine strains and established a PCR-based assay that could be used to: (a) rapidly diagnose the presence of myxoma virus in infected organs; (b) discriminate between field strain-infected and vaccinated rabbits and (c) differentiate between Borghi or SG33 vaccine strain.     

The epidemiology of varicella cases among children in Beijing's Fengtai District from 2008 to 2012

In recent years, the number of breakthrough cases of varicella (onset >42 days after vaccination) increased each year, and varicella outbreaks continue to occur in Beijing. Data from the Immunization Information System and the Infectious Disease Reporting System demonstrated that in Beijing's Fengtai District, the varicella breakthrough rate increased from 0.7% in 2008 to 2.5% in 2012 and showed an increased trend (P < 0.001). Among the varicella cases in children (age of 3–15 years), the number of breakthrough cases increased from 167 in 2008 to 622 in 2012, which was 45.2% (n = 1735) of the total child cases (n = 3842). From 2008 to 2012, a total of 62 outbreaks occurred; among the 787 affected child outbreak cases, 61% were vaccinated. Altogether, the results from this study indicated that 1-dose vaccination cannot sufficiently prevent the occurrence of breakthrough cases of varicella or control varicella outbreaks in Beijing's Fengtai District.     

The uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis in the community

We examined the uptake of rotavirus vaccine and its effectiveness in preventing acute gastroenteritis (AGE) in the community. Data on rotavirus vaccines purchases and AGE were extracted from the computerized database of a large health maintenance organization in Israel. The incidence of AGE requiring a physician visit during 2008-09 rotavirus season among vaccinated and non-vaccinated children were compared, and vaccine effectiveness was calculated as: (1 − Relative Risk) × 100. During the study period, the uptake of rotavirus vaccine (mostly monovalent) reached 55.1% (N = 19,108) of the studied cohort. The risk of AGE requiring a physician visit was 23.2% and 46.4% among vaccinated and unvaccinated children, respectively, yielding an effectiveness of 50.1% (95% CI: 47.5%, 52.6%). Rotavirus monovalent vaccine was highly effective in preventing AGE in the community.     

Efficacy of a divalent and a multivalent water-in-oil formulated vaccine against a highly virulent strain of Flavobacterium psychrophilum after intramuscular challenge of rainbow trout (Oncorhynchus mykiss)

Flavobacterium psychrophilum is a well-known pathogen causing significant problems in aquaculture worldwide. In recent years an increasing number of disease outbreaks caused by F. psychrophilum has been reported on juvenile and post smolts of rainbow trout (Oncorhynchus mykiss) in Norway. The current study was performed to assess the efficacy of two autogenous water-in-oil formulated vaccines containing whole cell antigens of F. psychrophilum to induce protective immunity against challenge. The vaccines were formulated either as multivalent (FLAVO AVM6) or divalent (FLAVO IPN) and administered by the intraperitoneal route. Intramuscular challenge with a field strain of F. psychrophilum was carried out 552 day degrees post vaccination, at a time when the FLAVO AVM6 and FLAVO IPN vaccinated groups had significantly higher antibody responses compared to the negative control. Results from the challenge study showed that the multivalent and the divalent vaccines had capacity to induce significant protection, with RPS₆₀ > 87% and RPS_end > 77.5% for both vaccines. The high level of protection seen in the vaccinated groups was also reflected in the reduced ulceration rates observed at the injection site. Combining our results demonstrate that vaccination with FLAVO AVM6 and FLAVO IPN induces responses capable of protecting rainbow trout against infections with F. psychrophilum.     

DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial

Background

We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED™ (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge.

Methods

Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 μg Trivalent influenza DNA vaccine, 2 μg Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus.

Results

Vaccination with 4 μg Trivalent or 2 μg Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 μg Trivalent group (N = 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = −1.5, 67.7) for ‘Any illness with or without fever’ and 53% for ‘Upper respiratory tract infection’ (95% CI = 8.0, 77.7).

Conclusion

It was concluded that PMED vaccination with 4 μg Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination.     

Clinical and immunologic predictors of influenza illness among vaccinated older adults

The diagnosis of influenza is often missed in older adults and illness presentation may be modified by prior vaccination. We evaluated the symptoms and immunologic markers predicting laboratory-confirmed influenza (LCI) among vaccinated older adults. In subjects with influenza-like illness (ILI), fever distinguished subjects with laboratory-confirmed influenza (LCI) from those with other ILI (39% vs. 12.5%, p = 0.009). In LCI subjects who did not seroconvert to influenza infection, pre-infection levels of the cytolytic mediator, granzyme B, correlated with fever (r = 1.000; p = 0.01) and the IFN-γ:IL-10 ratio (r = 0.999; p = 0.03), and increased following influenza infection in LCI vs. ILI subjects (p = 0.03). The cell-mediated immune response to influenza distinguishes A/H3N2 LCI from other ILI in older adults, and suggests a link between cell-mediated immunity and influenza illness severity in vaccinated older adults.     

HPV vaccine and adolescent males

In 2009, the United States approved quadrivalent HPV vaccine for males 9-26 years old, but data on vaccine uptake are lacking. We determined HPV vaccine uptake among adolescent males, as well as stage of adoption and vaccine acceptability to parents and their sons. A national sample of parents of adolescent males ages 11-17 years (n = 547) and their sons (n = 421) completed online surveys during August and September 2010. Analyses used multivariate linear regression. Few sons (2%) had received any doses of HPV vaccine, and most parents and sons were unaware the vaccine can be given to males. Parents with unvaccinated sons were moderately willing to get their sons free HPV vaccine (mean = 3.37, SD = 1.21, possible range 1-5). Parents were more willing to get their sons vaccinated if they perceived higher levels of HPV vaccine effectiveness (β = 0.20) or if they anticipated higher regret about their sons not getting vaccinated and later developing an HPV infection (β = 0.32). Vaccine acceptability was also modest among unvaccinated sons (mean = 2.98, SD = 1.13, possible range 1-5). Sons were more willing to get vaccinated if they perceived higher peer acceptance of HPV vaccine (β = 0.39) or anticipated higher regret about not getting vaccinated and later developing an HPV infection (β = 0.22). HPV vaccine uptake was nearly nonexistent a year after permissive national recommendations were first issued for males. Vaccine acceptability was moderate among both parents and sons. Efforts to increase vaccine uptake among adolescent males should consider the important role of peer acceptance and anticipated regret.     

Safety and efficacy of human rotavirus vaccine during the first 2 years of life in Asian infants: Randomised,double-blind,controlled study

This study evaluates the safety and efficacy against severe rotavirus gastroenteritis of the oral live attenuated human rotavirus vaccine RIX4414 (Rotarix™) during the first 2 years of life in Asian infants from high-income countries. Healthy infants were enrolled to receive 2 doses of RIX4414 (N = 5359) or placebo (N = 5349). From 2 weeks post-dose 2 to 2 years of age, vaccine efficacy was 96.1% (95%CI:85.1%; 99.5%) against severe rotavirus gastroenteritis, 100% (95%CI:80.8%; 100%) against wild-type G1P[8] and 93.6% (95%CI:74.7%; 99.3%) against circulating non-G1 rotavirus types. No intussusception cases were reported within 31 days post-vaccination. RIX4414 shows a good safety profile and offers high protection during the first 2 years of life with potentially significant public health impact in this population.     

Reproductive,productivity, and mortality outcomes in late-gestation gilts and their litters following simulation of inadvertent exposure to a modified-live vaccine strain of porcine reproductive and respiratory syndrome (PRRS) virus

The study evaluated the safety of a modified live-virus (MLV) porcine reproductive and respiratory syndrome (PRRS) vaccine in susceptible, pregnant gilts. To simulate inadvertent exposure secondary to postvaccination shedding of PRRS-MLV, seronegative gilts (n = 51) were exposed by IM vaccination at 90 days of gestation. Vaccinated and nonvaccinated, seronegative control gilts (n = 25) were maintained in separate facilities. The PRRS-MLV vaccine was given in a 2 mL dose on day 0. On day 7 all vaccinated gilts were PRRSV-PCR-positive for PRRSV and had responded serologically as determined by an ELISA. All control gilts remained PRRSV-PCR- and ELISA-negative throughout the study. Abortions did not occur in gilts from either group. The difference between vaccinated and control gilts in average number of piglets per litter (12.43 and 12.16, respectively), number of live births per litter (11.21 and 11.54), and mean piglet birth weight (3.22 and 3.26 lbs) were not significantly different. Piglets in the control group had significantly greater average daily gain versus piglets from vaccinated gilts (0.52 vs. 0.46 lbs, P < 0.0001). Preweaning mortality was significantly greater (P = 0.0023) in piglets from the vaccinated gilts (19.7% vs. 10.9%). A single gilt accounted for 18.2% of stillbirths in the vaccinated group. Air samples were borderline PRRSV-PCR-positive for PRRSV on days 29 and 32, after more than 98% of gilts had farrowed. Results demonstrated that vaccination of pregnant gilts at the time of peak fetal susceptibility was non-abortigenic and that the PRRS-MLV agent did not significantly affect reproductive outcomes. Lower ADG in piglets from vaccinated gilts may be due to PRRS-MLV viremia following transplacental or post-farrowing exposure. Air sampling results indicated that environmental contamination with PRRS-MLV shed from vaccinated gilts was minimal.     

First field trial of a transmissible recombinant vaccine against myxomatosis and rabbit hemorrhagic disease

As a novel approach for immunisation of wild rabbits, we have recently developed a transmissible vaccine against myxomatosis and rabbit hemorrhagic disease (RHD) based on a recombinant myxoma virus (MV) expressing the RHDV capsid protein [J. Virol. 74 (2000) 1114]. The efficacy and safety of the vaccine have been extensively evaluated under laboratory conditions. In this study, we report the first limited field trial of the candidate vaccine that was undertaken in an island of 34 Has containing a population of around 300 rabbits. Following administration by the subcutaneous route to 76 rabbits, the vaccine induced specific antibody responses against both myxomatosis and RHDV in all the inoculated rabbits. Furthermore, the recombinant virus exhibited a limited horizontal transmission capacity, promoting seroconversion of around 50% of the uninoculated rabbit population. No evidence of undesirable effects due to the recombinant virus field release was detected.     

Immunogenicity and protective efficacy of a psoralen-inactivated dengue-1 virus vaccine candidate in Aotus nancymaae monkeys

Psoralens are photoreactive compounds that cross-link pyrimidines after exposure to UVA radiation. In this experiment, we tested the protective efficacy of a psoralen-inactivated dengue vaccine candidate in non-human primates. Two groups of 7 Aotus nancymaae monkeys received either 10 ng per dose of inactivated DENV1 plus alum adjuvant or alum alone (controls). Doses were injected intradermally on days 0, 14, and 28. Monkeys then received a challenge inoculation of 1.1 × 10⁴ PFUs of WestPac 74 DENV-1 on day 132. At 62 days, only 1/7 vaccinated monkeys had detectable IgM, but IgG and neutralizing antibody remained detectable in 7/7. No IgM, IgG, or neutralizing antibody was detectable in control monkeys. DENV-1 viremia was detected after challenge in 3/7 vaccinated monkeys and 5/6 control monkeys (with one removed due to pregnancy) (p = 0.27), but days of viremia were reduced from 3.67 days/animal among controls to 0.71 days/animal among vaccinated monkeys (p = 0.051). Psoralen-inactivated DENV1 is immunogenic in Aotus nancymaae with a trend towards a reduction in days of viremia following experimental challenge.     

Acceptability of the human papillomavirus vaccine and reasons for non-vaccination among parents of adolescent sons

Routine administration of the quadrivalent human papillomavirus (HPV) vaccine has been recommended for 11–12-year-old males since 2011, but coverage remains low. In a U.S. national sample of parents of 11–17-year-old males (n = 779), 78.6% of parents reported their sons had not received the HPV vaccine. The most common reason for non-vaccination (56.7%) was “My doctor or healthcare provider has not recommended it.” Parents citing only logistical reasons for non-vaccination (e.g., lack of recommendation, access, or education, n = 384) reported significantly higher vaccine acceptability than parents reporting a combination of attitudinal (e.g., concerns about vaccine safety or efficacy) and logistical barriers (n = 92), while parents citing only attitudinal barriers (n = 73) reported the lowest level of vaccine acceptability. In sum, many parents are willing but have not vaccinated sons due to logistical barriers, most commonly lack of healthcare provider recommendation. These findings have important implications for increasing HPV vaccination coverage among adolescent males.     

The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9 ± 4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p < 0.0001) in both groups and were found to be protective (>0.35 μg/ml) in 87–100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p < 0.05). A ≥4-fold increase of the baseline titers to ≥5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p = 0.0697). No patient developed vaccine-associated serious adverse events or disease flares.