Effect of high and low levels of maternally derived antibodies on porcine circovirus type 2 (PCV2) infection dynamics and production parameters in PCV2 vaccinated pigs under field conditions

The present study aimed to compare the efficacy of a porcine circovirus type 2 (PCV2) commercial vaccine in terms of average daily weight gain (ADWG) as well as infection dynamics in pigs with different maternally derived antibody (MDA) levels. A total of 337 animals from a PCV2 subclinically infected farm were distributed into two groups based on weight and PCV2 antibody levels (high [H] or low [L]) at 2 weeks of age. One week later, these animals were subdivided in four groups according to the treatment received. Vaccinated pigs (H-V and L-V) received 1 mL of a commercial vaccine and NV (H-NV and L-NV) received 1 mL of PBS. All piglets were subsequently bled at 7, 12, 18, 22 and 25 weeks of age and weighted at 12 and 25 weeks of age. V animals showed significantly lower PCV2 infection rates and viral load as well as higher ELISA S/P ratios and ADWG than NV ones. Compared with H-V piglets, L-V pigs showed numerically lower PCV2 infection rates, lower area under the curve of viral load, an earlier seroconversion and a numerically, but not significantly, higher ADWG. In this study, MDA did not seem to interfere with the effect of PCV2 vaccination on ADWG. However, only when a small subpopulation of pigs with the highest ELISA S/P ratios at vaccination was considered, an apparent interference of vaccine efficacy on ADWG was noticed. Therefore, the impact of the putative interference under field conditions is probably negligible for most farms.     

Porcine reproductive and respiratory syndrome virus (PRRSv) modified-live vaccine reduces virus transmission in experimental conditions

Some vaccination strategies have shown good results in reducing the clinical outcomes of PRRS. Nevertheless the effect of vaccines on viral transmission is poorly described, so we aimed to fill this gap with the present study. Twelve Specific Pathogen Free (SPF) piglets, vaccinated against PRRSv at 3 weeks of age (Porcilis PRRS ID^®, MSD), were inoculated at 31 days post-vaccination with a heterologous genogroup 1.1 strain, and put in contact with 12 vaccinated piglets during 49 days. The same protocol was carried out simultaneously with SPF non-vaccinated piglets. Piglets were monitored individually for clinical symptoms on a daily basis and individual blood samples were taken twice a week. In inoculated piglets, the genome viral load specific to the inoculated strain was reduced and viraemia shortened in vaccinated piglets (28 days versus 38 days in non vaccinated piglets). In contact pigs, the challenge strain was detected in the serum of only one vaccinated piglet whereas it was detected in all contact non-vaccinated piglets. Transmission parameters were estimated by a Bayesian analysis of transmission data in the two groups. The estimated transmission rate was 10-times lower in vaccinated than in non-vaccinated piglets and the duration of infectiousness was reduced, leading to a reproduction ratio R significantly lower (0.30 [0.05–0.96] versus 5.42 [2.94–9.04] in non vaccinated piglets). Hence, in our experimental conditions, vaccination was able to decrease considerably PRRSv spread. A complementary evaluation in field conditions would be required to identify circumstances associated with infection control failures that can be observed in pig farms.     

Effect on nasopharyngeal pneumococcal carriage of replacing PCV7 with PCV13 in the Expanded Programme of Immunization in The Gambia

IntroductionIn 2011, two years after the introduction of 7-valent Pneumococcal conjugate vaccine (PCV7), the Gambian immunization programme replaced PVC7 with PCV13 (13-valent). Our objective was to assess the additional impact of PCV13 on prevalence of pneumococcal nasopharyngeal carriage.MethodsWe recruited healthy Gambian infants who had received three PCV doses. Nasopharyngeal swabs were collected from infants and their mothers during two cross-sectional surveys (CSS) conducted in infants vaccinated with PCV7 (CSS1) and vaccinated with PCV13 (CSS2). Pneumococci were isolated and serotyped following standardized methods. Whole genome sequencing was performed on non-typable pneumococcus isolated in CSS1 and CSS2.Results339 and 350 infants and their mothers were recruited in CSS1 and CSS2, respectively. Overall prevalence of pneumococcal carriage was 85.4% in infants. Among infants, prevalence of vaccine type (VT) carriage was lower in CSS2 [9.4% versus 4.9% (p = 0.025) for PCV7-VT; 33.3% versus 18.3% (p < 0.001) for PCV13-VT and 23.9% versus 13.7% (p = 0.001) for the 6 additional serotypes included in PCV13]. At CSS2, there was a decrease of serotypes 6A (from 15.3% to 5.7%, p < 0.001) and 19F (from 5.6% to 1.7%, p = 0.007), and an increase of non-typable pneumococci (0.3–6.0%, p < 0.001), most of which (82.4%) were from typable serotype backgrounds that had lost the ability to express a capsule. Prevalence of overall and VT carriage in mothers was similar in CSS1 and CSS2.ConclusionsReplacing PCV7 for PCV13 rapidly decreased prevalence of VT carriage among vaccinated Gambian infants. An indirect effect in mothers was not observed yet. Vaccine-driven selection pressure may have been responsible for the increase of non-typable isolates.     

A novel subunit vaccine co-expressing GM-CSF and PCV2b Cap protein enhances protective immunity against porcine circovirus type 2 in piglets

Porcine circovirus type 2 (PCV2) causes porcine circovirus-associated disease. Capsid (Cap) protein of PCV2 is the principal immunogenic protein that induces neutralizing antibodies and protective immunity. GM-CSF is an immune adjuvant that enhances responses to vaccines. In this study, recombinant baculoviruses Ac-Cap and Ac-Cap-GM-CSF expressing the Cap protein alone and co-expressing the Cap protein and porcine GM-CSF, respectively, were constructed successfully. The target proteins were analyzed by western blotting and IFA. Further, these proteins were confirmed by electron microscopy, which showed that Cap proteins could self-assemble into virus-like particles having diameters of 17–25 nm. Animal experiments showed that pigs immunized with Cap-GM-CSF subunit vaccine showed significantly higher levels of PCV2-specific antibodies and neutralizing antibodies than pigs immunized with the Cap subunit vaccine and a commercial vaccine (Ingelvac CircoFLEX; P < 0.05). After PCV2 wild strain challenged, Pigs receiving the Cap-GM-CSF subunit vaccine showed significantly higher average daily weight gain after wild-type PCV2 challenge than pigs receiving the other three vaccines (P < 0.05). None of PCV2 DNA was detected in all immunized animals, except control animals immunized with phosphate-buffered saline. These results indicated that GM-CSF was a powerful immunoadjuvant for PCV2 subunit vaccines because it enhanced humoral immune response and improved immune protection against PCV2 infection in pigs. Thus, the novel Cap-GM-CSF subunit vaccine has the potential to be used as an effective and safe vaccine candidate against PCV2 infection.     

Impact of the 13-valent pneumococcal conjugate vaccine on Streptococcus pneumoniae multiple serotype carriage

IntroductionPneumococcal multiple serotype carriage is important for evolution of the species and to understand how the pneumococcal population is changing with vaccination. We aimed to determine the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on multiple serotype carriage.Methods and materialsNasopharyngeal samples from fully vaccinated pneumococcal carriers (4 doses of PCV13, n = 141, aged 18–72 months) or from non-vaccinated pneumococcal carriers (0 doses of any PCV, n = 140, same age group) were analyzed. Multiple serotype carriage was evaluated by DNA hybridization with a molecular serotyping microarray that detects all known serotypes.ResultsVaccinated children had a lower prevalence of multiple serotype carriage than the non-vaccinated group (20.6% vs 29.3%, p = 0.097), and a significantly lower proportion of PCV13 serotypes (6.4% vs 38.5%, p = 0.0001). PCV13 serotypes found among vaccinated children were mostly detected as a minor serotype in co-colonization with a more abundant non-vaccine serotype. Vaccinated children were colonized by a significantly higher proportion of commensal non-pneumococcal Streptococcus spp. (58.2% vs 42.8%, p = 0.012). In vaccinated children there were significantly less non-vaccine type (NVT) co-colonization events than expected based on the distribution of these serotypes in non-vaccinated children.ConclusionsThe results suggest that vaccinated children have lower pneumococcal multiple serotype carriage prevalence due to higher competitive abilities of non-vaccine serotypes expanding after PCV13 use. This might represent an additional benefit of PCV13, as decreased co-colonization rates translate into decreased opportunities for horizontal gene transfer and might have implications for the evolution and virulence of pneumococci.     

Immunogenicity and immunoprotection of porcine circovirus type 2 (PCV2) Cap protein displayed by Lactococcus lactis

The capsid (Cap) protein, an important immunoprotective protein of porcine circovirus type 2 (PCV2), was expressed on the cell surface of the Gram-positive food-grade bacterium, Lactococcus lactis. Cap protein was fused to the peptidoglycan binding domain (known as the protein anchor domain, PA) of the lactococcal AcmA cell-wall hydrolase. The Cap protein fusion was non-covalently rebound to the surface of non-genetically modified, non-living high-binder L. lactis cells (designated Gram-positive enhancer matrix (GEM) particles). Expression of the recombinant GEM-displaying capsid protein (GEM-PA-Cap) was verified by Western blotting and immunofluorescence and transmission electron microscopy assays. To evaluate the immunogenicity of the recombinant Cap protein (rCap), 20 PCV2-seronegative piglets were immunized with the GEM-PA-Cap subunit vaccine, GEM alone, or phosphate-buffered saline (PBS, challenge control and empty control). Each group consisted of five piglets. The results showed that the level of PCV2-specific antibodies in piglets immunized with the GEM-PA-Cap subunit vaccine was significantly higher than that of the piglets immunized with GEM alone or the control group at all the time points post-vaccination (P < 0.01). After challenge with the PCV2 wild-type strain, piglets that received the GEM-PA-Cap subunit vaccine showed significantly higher average daily weight gain (DWG) and shorter fever duration than the other two groups (P < 0.001). Furthermore, a significant reduction in the gross lung lesion scores and lymph node lesion scores was noted in the GEM-PA-Cap-immunized group compared with the scores of the GEM or PBS-treated group (P < 0.01). The results suggest that recombinant rCap displayed by L. lactis GEM particles provided the piglets with significant immunoprotection from PCV2-associated disease. Thus, the novel GEM-PA-Cap subunit vaccine has potential to be considered an effective and safe candidate vaccine against PCV2 infection in piglets.     

Efficacy of a new bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae (Fostera™ PCV MH) under experimental conditions

The objective of this study was to evaluate the efficacy of a new bivalent vaccine (Fostera™ PCV MH, Zoetis) of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae in growing pigs under experimental conditions. A total of 80 pigs were randomly divided into 8 groups (10 pigs per group). The pigs were administered the bivalent vaccine intramuscularly as a 2.0 mL dose at 21 days of age based on the manufacturer's instructions. Three weeks after vaccination, the pigs were inoculated with either PCV2 (intranasal route) or M. hyopneumoniae (intratracheal route) or both. Regardless of the type of inoculation, vaccinated pigs after challenge exhibited effective reduction of clinical signs, PCV2 viremia levels and mycoplasma nasal shedding, and lung and lymphoid lesion when compared to unvaccinated challenged pigs. Vaccinated challenged pigs had significantly higher (P < 0.05) levels of PCV2-specific neutralizing antibodies, and numbers of PCV2-and M. hyopneumoniae-specific interferon-γ secreting cells compared to unvaccinated challenged pigs. This study demonstrates that the bivalent vaccine is able to protect pigs against either PCV2 or M. hyopneumoniae infection or both based on clinical, microbiological, immunological, and pathological evaluation.     

Efficacy of a reformulated inactivated chimeric PCV1-2 vaccine based on clinical,virological, pathological and immunological examination under field conditions

Inactivated chimeric porcine circovirus (PCV) 1-2 vaccine was initially taken off the market due to concerns that the vaccine virus was not killed and thus further replicated and spread in the pig population. In August 2011, a reformulated inactivated chimeric PCV1-2 vaccine re-entered the market. The efficacy of the reformulated inactivated chimeric PCV1-2 vaccine was evaluated under field conditions for registration as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based on their history of postweaning multisystemic wasting syndrome (PMWS). On each farm, a total of 50 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated at 3 weeks of age and (ii) non-vaccinated. Clinical examination indicated that vaccinated animals displayed an improved average daily weight gain (672.2 g/day vs. 625 g/day; difference of +47.3 g/day; P < 0.05) and a reduced time to market (177 days vs. 183 days; difference of −6 days; P < 0.05). Virological examination indicated that vaccinated animals displayed a reduced PCV2 load in the blood and nasal swabs compared to non-vaccinated animals. Pathological examination indicated that vaccination of pigs against PCV2 effectively reduced the number of PMWS-associated microscopic lesions and the PCV2 load in lymphoid tissues compared to non-vaccinated animals in the 3 herds. Immunological examination indicated that vaccinated animals induced PCV2-specific neutralizing antibodies (NA) and interferon-γ-secreting cells (IFN-γ-SCs). A reduction in the PCV2 load in the blood coincided with the appearance of both PCV2-specific NA and IFN-γ-SCs in the vaccinated animals. The number of CD4⁺ cells was decreased in non-vaccinated animals compared to vaccinated animals. The reformulated inactivated chimeric PCV1-2 vaccine seems to be very effective in controlling PCV2 infection based on clinical, virological, pathological, and immunological evaluations under field conditions.     

A commercial porcine circovirus (PCV) type 2a-based vaccine reduces PCV2d viremia and shedding and prevents PCV2d transmission to naïve pigs under experimental conditions

Porcine circovirus type 2 (PCV2) vaccination has been effective in protecting pigs from clinical disease and today is used extensively. Recent studies in vaccinated populations indicate a major PCV2 genotype shift from the predominant PCV2 genotype 2b towards 2d. The aims of this study were to determine the ability of the commercial inactivated PCV2a vaccine Circovac® to protect pigs against experimental challenge with a 2013 PCV2d strain and prevent transmission. Thirty-eight pigs were randomly divided into four groups with 9–10 pigs per group: NEG (sham-vaccinated, sham-challenged), VAC (PCV2a-vaccinated, sham-challenged), VAC + CHAL (PCV2a-vaccinated and PCV2d-challenged), and CHAL (sham-vaccinated, PCV2d-challenged). Vaccination was done at 3 weeks of age using Circovac® according to label instructions. The CHAL and VAC + CHAL groups were challenged with PCV2d at 7 weeks of age and all pigs were necropsied 21 days post-challenge (dpc). The VAC-CHAL pigs seroconverted to PCV2 by 21 days post vaccination (dpv). At PCV2d challenge on 28 dpv, 3/9 VAC and 1/9 VAC + CHAL pigs were seropositive. NEG pigs remained seronegative for the duration of the study. Vaccination significantly reduced PCV2d viremia (VAC + CHAL) at dpc 14 and 21, PCV2d fecal shedding at dpc 14 and 21 and PCV2d nasal shedding at dpc 7, 14 and 21 compared to CHAL pigs. Vaccination significantly reduced mean PCV2 antigen load in lymph nodes in VAC + CHAL pigs compared to CHAL pigs. When pooled serum or feces collected from VAC + CHAL and CHAL pigs at dpc 21 were used to expose single-housed PCV2 naïve pigs, a pooled fecal sample from CHAL pigs contained infectious PCV2 whereas this was not the case for VAC + CHAL pigs suggesting reduction of PCV2d transmission by vaccination. Under the study conditions, the PCV2a-based vaccine was effective in reducing PCV2d viremia, tissue loads, shedding and transmission indicating that PCV2a vaccination should be effective in PCV2d-infected herds.     

Virus replication kinetics and pathogenesis of infection with H7N9 influenza virus in isogenic guinea pigs upon intratracheal inoculation

Since 2013, avian influenza viruses of subtype H7N9 have been transmitted from poultry to humans in China and caused severe disease. Concerns persist over the pandemic potential of this virus and further understanding of immunity and transmission is required. The isogenic guinea pig model uniquely would allow for investigation into both. Eighteen female isogenic guinea pigs 12–16 weeks were inoculated intratracheally with either A/H7N9 virus (n = 12) or PBS (n = 6) and sacrificed on days 2 and 7 post-inoculation. Nasal and pharyngeal swabs were taken daily to assess viral replication kinetics and necropsies were performed to study pathogenesis. All animals showed peak virus titers in nasal secretions at day 2 post-inoculation and by day 7 post-inoculation infectious virus titers had decreased to just above detectable levels. At day 2, high virus titers were found in nasal turbinates and lungs and moderate titers in trachea and cerebrum. At day 7, infectious virus was detected in the nasal turbinates only. Histology showed moderate to severe inflammation in the entire respiratory tract and immunohistochemistry (IHC) demonstrated large numbers of viral antigen positive cells in the nasal epithelium at day 2 and fewer at day 7 post-inoculation. A moderate number of IHC positive cells was observed in the bronchi(oli) and alveoli at day 2 only. This study indicates that isogenic guinea pigs are a promising model to further study immunity to and transmission of H7N9 influenza virus.     

A Porcine circovirus type 2b (PCV2b)-based experimental vaccine is effective in the PCV2b-Mycoplasma hyopneumoniae coinfection pig model

Porcine circovirus type 2 (PCV2) is one of the major swine pathogens causing high economic losses due to PCV2-associated disease (PCVAD). PCV2 infection is not only immunosuppressive by damaging lymphoid tissues but is also exacerbated by co-infections with other pathogens including Mycoplasma hyopneumoniae. While PCV2 can be divided into several genotypes, currently only PCV2a, PCV2b and PCV2d are globally prevalent and considered of major importance. Most commercial PCV2 vaccines are based on PCV2a isolates; however, the high prevalence of PCV2b and PCV2d in the global pig population is raising concerns among pig veterinarians. The objective of this study was to evaluate the efficacy of an experimental PCV2b-based subunit vaccine in a combined PCV2b and M. hyopneumoniae coinfection model. Briefly, a total of 49 PCV2- and M. hyopneumoniae-free 3-week-old pigs were randomly divided into four groups: A non-vaccinated, non-infected NEG-CONTROL group, a non-vaccinated, PCV2b-infected, POS-CONTROL group, and two vaccinated and PCV2b-infected groups (SINGLE-VAC, DUAL-VAC). SINGLE-VAC and DUAL-VAC pigs were vaccinated at 3 weeks of age and DUAL-VAC pigs received a booster dose at 5 weeks of age. All pigs, except NEG-CONTROLs, were experimentally infected with M. hyopneumoniae 28 days after initial vaccination and challenged with PCV2b one week later. The pigs were necropsied 21 days after PCV2b challenge. Prior to PCV2b challenge, both vaccinated groups had detectable humoral and cell-medicated immune responses to PCV2. Vaccination significantly reduced PCV2b viremia and also reduced or eliminated PCV2-associated lymphoid lesions compared to the POS-CONTROL pigs. Under the study conditions, an experimental PCV2b vaccine protected conventional growing pigs against PCV2b viremia and associated lesions in a coinfection model with some advantages of the two-dose regimen versus the one dose regimen. Both protocols induced neutralizing antibodies against PCV2a and PCV2d prior to challenge.     

Porcine kobuvirus 1 in healthy and diarrheic pigs: Genetic detection and characterization of virus and co-infection with rotavirus A

The porcine kobuvirus 1 (PKV-1) is believed to be an enteric virus. To investigate the prevalence of PKV-1 in pigs, virus was detected by RT-PCR in rectal swabs originating from 414 healthy and diarrheic pigs of different age categories on farms in Slovakia. Among all ages of animals, PKV-1 was detected equally in diarrheic (63.8%) and clinically healthy (62.9%) pigs. PKV-1 was more often detected in diarrheic (74.6%) than in healthy (64.4%) suckling piglets (< 28 days) but data was not statistically significant. Results in weaned (28–70 days) and fattening (> 70 days) of both healthy and diarrheic pigs were inconsistent ranging in interval 56.2% to 67.9%. This study did not confirm a clear relationship of PKV-1 infection with diarrhea in pigs. Rotavirus A infection was detected among the same animals in 39% diarrheic and 9.2% healthy suckling piglets (p < 0.001) confirming rotavirus as a causative agent of diarrhea in this age group. The difference was not significant in older pigs with both diarrheic and healthy pigs being infected within a range of 0% to 12.2%. Co-infection with PKV-1 and rotavirus A was detected overall in 5.6% of healthy and in 13.5% of diarrheic pigs and was highest in suckling piglets (33.9%). The PKV-1sequences from pigs in Slovakia were analyzed at the genetic level in the partial 3D gene region for the first time. The viral sequences were grouped in phylogenetic clusters according to their farm of origin. When compared with 157 nucleotide sequences originating from pig samples of different countries around the world Slovakian PKV-1 sequences were clustered in the phylogenetic tree with Asian sequences but not with nucleotide sequences from the neighbouring countries of Czech Republic or Hungary.     

Protection of non-human primates against glanders with a gold nanoparticle glycoconjugate vaccine

The Gram-negative Burkholderia mallei is a zoonotic pathogen and the causative agent of glanders disease. Because the bacteria maintain the potential to be used as a biothreat agent, vaccine strategies are required for human glanders prophylaxis. A rhesus macaque (Macaca mulatta) model of pneumonic (inhalational) glanders was established and the protective properties of a nanoparticle glycoconjugate vaccine composed of Burkholderia thailandensis LPS conjugated to FliC was evaluated. An aerosol challenge dose of ∼1 × 10⁴ CFU B. mallei produced mortality in 50% of naïve animals (n = 2/4), 2–3 days post-exposure. Although survival benefit was not observed by vaccination with a glycoconjugate glanders vaccine (p = 0.42), serum LPS-specific IgG titers were significantly higher on day 80 in 3 vaccinated animals who survived compared with 3 vaccinated animals who died. Furthermore, B. mallei was isolated from multiple organs of both non-vaccinated survivors, but not from any organs of 3 vaccinated survivors at 30 days post-challenge. Taken together, this is the first time a candidate vaccine has been evaluated in a non-human primate aerosol model of glanders and represents the initial step for consideration in pre-clinical studies.     

Vaccine effectiveness of PCV13 in a 3 + 1 vaccination schedule

ObjectiveTo assess the vaccine effectiveness (VE) of PCV13 for invasive pneumococcal disease (IPD) regarding the extra six serotypes with a 3 + 1 schedule in Germany.MethodsActive surveillance for IPD in children <16 years eligible for PCV13 vaccination. We used the Broome method and logistic regression to estimate VE.ResultsData on 164/304 reported IPD cases were informative and met the inclusion criteria. VE for the extra six serotypes was 88% [95% confidence interval (CI): 73; 95] and 83% [56; 94] for at least one and for at least two doses respectively. VE for the complete 3 + 1 vaccination schedule was not conclusive because of a wide 95% CI. For serotype 3 VE appeared to be zero with an even wider 95% CI.ConclusionPCV13 VE against the extra six serotypes with the 3 + 1 schedule in Germany was only marginally higher compared to previously published data for the 2 + 1 schedule.     

Impact of PCV7/PCV13 introduction on invasive pneumococcal disease (IPD) in young children: Comparison between meningitis and non-meningitis IPD

BackgroundThe worldwide introduction of pneumococcal conjugate vaccines (PCV) into National Immunization Programs resulted in rapid and substantial reduction of invasive pneumococcal disease (IPD) rates in children. However, the reduction of meningitis vs. non-meningitis IPD (nm-IPD) was not yet fully elucidated. We compared 7-valent and 13-valent PCV (PCV7 and PCV13) impact on pneumococcal-meningitis vs. nm-IPD in Israeli children <5 years.MethodsWe conducted an ongoing nationwide, prospective, population-based, active surveillance. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All pneumococcal isolates (blood and/or CSF) from IPD episodes in children <5 years from July 2000 through June 2015 were included. Extrapolation for missing serotypes (34.7% of all isolates) was conducted.Results4163 IPD cases were identified; 3739 nm-IPD (89.8%) and 424 meningitis (10.2%). During the pre-PCV period (2000–2008), children <12 months constituted 52.1% and 33.7% of meningitis and nm-IPD, respectively (p < 0.001). The respective proportions of non-PCV13 serotypes (non-VT) were 18.2% vs. 10.1%, (p < 0.001).Comparing the last study year (2014–2015) to the mean of pre-PCV period, meningitis incidence in children <5 years decreased non-significantly by 27%, while nm-IPD decreased significantly by 69%. Dynamic rates of meningitis and nm-IPD caused by PCV13 serotypes were similar, with 93% and 95% overall reductions, respectively. However, non-VT increased in meningitis relatively to nm-IPD, mainly in children <24 months. Serotype 12F rose sharply and significantly since 2009–2010 through 2014–2015 (28.6% of all non-VT meningitis in children <24 m).ConclusionsThe overall impact of PCV7/PCV13 in children <5 years in Israel was less prominent in meningitis than in nm-IPD. This could be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar. Continuous monitoring of meningitis and nm-IPD is warranted.     

Safety of classical swine fever virus vaccine strain LOM in pregnant sows and their offspring

The present study aimed to evaluate the safety of the classical swine fever virus (CSFV) vaccine strain LOM in pregnant sows. Pregnant sows with free CSFV antibody were inoculated with a commercial LOM vaccine during early pregnancy (day 38; n = 3) or mid-pregnancy (days 49–59; n = 11). In pregnant sows vaccinated during the early stages of gestation, abortion (day 109) was observed in one case, with two stillbirths and seven mummified fetuses. The viability of live-born piglets was 34.9% in sows vaccinated during mid-pregnancy compared with 81.8% in the control group. Post-mortem examination of the organs of the sows and piglets did not reveal any pathological lesions caused by CSFV; however, CSFV RNA was detected in the organs of several vaccinated sows and their litters. The LOM strain was transmitted from sows with free CSFV antibody to their fetus, but did not appear to induce immune tolerance in the offspring from vaccinated pregnant sows. Side effects were not observed in pregnant sows with antibody to the LOM strain: transmission from sow to their litters and stillbirth or mummified fetuses. The LOM strain may induce sterile immunity and provide rapid, long-lasting, and complete protection against CSFV; however, it should be contraindicated in pregnant sows due to potential adverse effects in pregnant sows with free CSFV antibody.     

The impact of private use of PCV7 in 2009 and 2010 on serotypes and antimicrobial resistance of Streptococcus pneumoniae carried by young children in Portugal: Comparison with data obtained since 1996 generating a 15-year study prior to PCV13 introduction

In Portugal, the 7-valent pneumococcal conjugate vaccine (PCV7) was not introduced in the national immunization plan but was commercially available between 2001 and 2010. We studied serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae carried by children in 2009 and 2010. Vaccination with PCV7 was extracted from children's immunization bulletins and information on recent antimicrobial consumption was obtained through a questionnaire. For comparison, we included data from previous studies conducted since 1996: 1996–1999, 2001–2003, 2006–2007. Pneumococci were isolated from nasopharyngeal samples of 1092 children up to six years old attending day-care in an urban area. Among these, 76% (819/1070) were vaccinated and 62% (677/1092) carried pneumococci. In 2009–2010, serotype replacement was extensive. Carriage of PCV7 serotypes was 4.9% and 5.8%, in 2009 and 2010, respectively, with the majority being of serotype 19F (carried by 4.3% and 4.6% of all participants, respectively). Colonization by serotype 19F was associated with vaccine status (7.7% (19/248) of non-vaccinees vs. 3.5% (29/818) of PCV7-vaccinees, p = 0.010). Carriage of serotype 19A was high in 2009 and 2010 (8.6% of all participants) consistent with values already observed in 2007; carriage of serotype 6A was <1% (10/1092), indicating a major decline after 2007 (5.8% or 31/538, p < 0.001). Non-vaccine serotypes increased and serotype 6C became the most frequently carried serotype in 2010 (11.2% (54/481)). High-level resistance to penicillin (MIC ≥2 mg/L) showed a decreasing trend (p < 0.001), whereas resistance to both penicillin and erythromycin increased (p < 0.001) and was detected in 15–20% of all isolates in 2009–2010, most of which were non-vaccine serotypes. Antimicrobial use decreased over time (p < 0.001). In conclusion, widespread private use of PCV7 has impacted on colonization leading to near elimination of all PCV7 serotypes except for serotype 19F. Antimicrobial consumption declined but it may be too soon to observe generalized changes in antimicrobial resistance rates.     

Attempts to enhance cross-protection against porcine reproductive and respiratory syndrome viruses using chimeric viruses containing structural genes from two antigenically distinct strains

Due to significant antigenic variations between field isolates of porcine reproductive and respiratory syndrome virus (PRRSV), suboptimal cross-protection between different viruses impedes the effective control of PRRS via vaccination. Our previous study showed that chimeric viruses containing mixed structural genes from two distinct strains (VR2332 and JA142) of PRRSV were highly susceptible to the viral neutralizing activity of antisera generated against both parental strains. In this study, three chimeric viruses (JAP5, JAP56 and JAP2–6) were constructed by replacing ORF5, ORFs 5 and 6, and ORFs 2-6 of VR2332 with the corresponding genes of JA142, respectively, and their ability to confer cross-protection against challenge with the VR2332 and JA142 strains was evaluated in vivo. A total of 114 pigs were divided into 6 groups, and each group was intramuscularly injected with one of the 3 chimeric viruses (n = 16 pigs per group), VR2332 (n = 24), JA142 (n = 24), or sham inoculum (n = 18). At 44 days post-inoculation (dpi), these pigs were further divided into 15 groups (n = 6 or 8 pigs per group) and intranasally challenged with VR2332, JA142, or sham inoculum. All pigs inoculated with one of the chimeric viruses prior to challenge had lower viremia levels than the challenge control pigs. Prior inoculation with JAP56 markedly decreased viremia to nearly undetectable levels in pigs challenged with either VR2332 or JA142. These results suggest that chimeric viruses harboring mixed structural genes from two distinct PRRSV strains can provide protection against both donor viruses.     

Frequency of complications and the effects of pneumococcal vaccination in young children with acute respiratory tract infection

BackgroundAcute respiratory infection (ARI) is the most frequent reason for children being seen by doctors worldwide. We aimed to estimate the frequency of complications in children aged 6–23 months during ARI episode and to evaluate risk factors present on recruitment associated with complications after the universal implementation of pneumococcal vaccine (PCV10) in our region.MethodsThis prospective cohort enrolled children who had shown ARI for up to 7 days and who were subsequently followed up 14–21 days after, in Salvador, Brazil. Data on recruitment were registered. The vaccine card was personally checked. Complication was defined when hospitalization, pneumonia or acute otitis media (AOM) were informed during the follow-up visit. Pneumonia and AOM were diagnosed by a doctor. Multiple logistic regression analysis was performed.ResultsOf 576 children, 422 (73%) returned and 79 (19%; 95%CI: 15–23%) had complications. The mean interval between admission and follow-up was 23 ± 13 days. Pneumonia (n = 47; 11%), hospitalization (n = 28; 7%), and AOM (n = 17; 4%) were reported. Most of the patients presented one complication (n = 66; 84%) followed by two (n = 13; 16%). Report of fever (92% versus 79%; OR [95%CI]: 2.90 [1.18–7.14]), bird at home (24% versus 14%; OR [95%CI]: 2.13 [1.07–4.26]), ronchi (48% versus 36%; OR [95%CI]: 2.06 [1.16–3.67]) or crackles (17% versus 7%; OR [95%CI]: 2.36 [1.04–5.38]) on auscultation were directly associated with complications whereas PCV10 (59% versus 75%; OR [95%CI]: 0.46 [0.26–0.82]) was inversely associated. Bird at home (OR [95%CI]: 5.80 [1.73–19.38]) and ronchi (OR [95%CI]: 6.39 [1.96–20.85]) were associated with AOM; PCV10 was inversely associated with AOM (OR [95%CI]: 0.16 [0.05–0.52]). Crackles were associated with pneumonia (OR [95%CI]: 2.55 [1.01–6.40]).ConclusionsOne fifth of the children presented complications. PCV10 was independently associated with lower odds of development of AOM. Bird at home and ronchi are risk factors of otitis. Crackles are associated with pneumonia.