The impact of porcine circovirus associated diseases on live attenuated classical swine fever vaccine in field farm applications

Porcine circovirus associated diseases (PCVADs) are among the most important diseases affecting the worldwide swine industry. Vaccination against porcine circovirus type 2 (PCV2) infection has been utilized for disease control and effectively reduces clinical signs of PCVADs. To evaluate the efficacy of the PCV2 vaccine in field farms, we conducted a trial using conventional pigs immunized with the subunit PCV2 vaccine followed by PCV2 challenge. Immunized pigs demonstrated lower serum viral loads, less viral antigen staining in lymph nodes, and higher average daily weight gain, confirming the protective efficacy of the vaccine. However, low levels of PCV2 infection were still detected in vaccinated pigs after challenge, suggesting that the PCV2 vaccine was unable to eradicate the virus, which could lead to asymptomatic PCV2 subclinical infection (PCV2-SI) in pig farms. Additionally, PCV2 infection is a risk factor for impaired pig immune response development during the weaning to growth stages, which is a crucial period to receive vaccines against classical swine fever (CSF). Therefore, the impact of PCV2-SI or PCV2-systemic disease (PCV2-SD) on live attenuated CSF vaccine was investigated. After PCV2 challenge, there was no difference in levels of classical swine fever virus (CSFV) neutralizing antibodies (NA) between pigs with PCV2-SD and PCV2-SI, suggesting that the efficacy of CSF vaccine was compromised. Moreover, results of long-term monitoring of CSFV NA titers in PCV2-SI pigs with minimized interference by maternally-derived antibodies suggested that serum PCV2 viral loads greater than 10² copies/mL may compromise the efficacy of CSF vaccine. Overall, a conventional pig model was established to demonstrate the impaired efficacy of the subunit PCV2 vaccine and its impact on the CSF vaccine in vaccination-challenge trials. Additionally, the impaired efficacy of the PCV2 vaccine resulted in increased PCV2-SI, eventually leading to compromised the live attenuated CSF vaccine induced NA response in field farm applications.     

Protective immunity against influenza virus challenge by norovirus P particle-M2e and HA2-AtCYN vaccines in chickens

Development of a broadly reactive influenza vaccine that can provide protection against emerging type A influenza viruses is a big challenge. We previously demonstrated that a vaccine displaying the extracellular domain of the matrix protein 2 (M2e) on the surface loops of norovirus P-particle (M2eP) can partially protect chickens against several subtypes of avian influenza viruses. In the current study, a chimeric vaccine containing a conserved peptide from the subunit 2 of hemagglutinin (HA) glycoprotein (HA2) and Arabidopsis thaliana cyanase protein (AtCYN) (HA2-AtCYN vaccine) was evaluated in 2-weeks-old chickens. Depending on the route of administration, the HA2-AtCYN vaccine was shown to induce various levels of HA2-specific IgA in tears as well as serum IgG, which were associated with partial protection of chickens against tracheal shedding of a low pathogenicity H5N2 challenge virus. Furthermore, intranasal administration with a combination of HA2-AtCYN and M2eP vaccines resulted in enhanced protection compared to each vaccine alone. Simultaneous intranasal administration of the vaccines did not interfere with secretory IgA induction by each vaccine. Additionally, significantly higher M2eP-specific proliferative responses were observed in peripheral blood mononuclear cells of all M2eP-vaccinated groups when compared with the mock-vaccinated group. Although tripling the number of M2e copies did not enhance the protective efficacy of the chimeric vaccine, it significantly reduced immunodominance of P-particle epitopes without affecting the robustness of M2e-specific immune responses. Taken together, our data suggests that mucosal immunization of chickens with combinations of mechanistically different cross-subtype-conserved vaccines has the potential to enhance the protective efficacy against influenza virus challenge.     

Are refugees arriving in Denmark an under-immunised group for measles? A cross-sectional serology study

BackgroundIn 2018, Europe faced the highest number of Measles cases in a decade. In Denmark, the childhood vaccination programme has a coverage of approximately 90%. To eliminate the disease, vaccine coverage needs to be above the herd immunity threshold of 95%. This can be even more difficult to obtain, when vaccination programmes break down due to war, natural disasters etc. and concern has been raised, that unvaccinated refugees could facilitate spread of measles when migrating.MethodsIn order to address this concern, we tested 513 newly arrived refugees and family reunified refugees aged between 0 and 70 years for measles IgG antibodies. The participants were tested as part of a general health assessment between May 2016 and October 2018. In the cohort, 50% were males and the majority came from Syria (55%).ResultsWe found that 85% of the total group of refugees had immunity against measles. The 15% lacking antibodies were evenly distributed between the various countries of origin. Moreover, we found immunity to increase with age, leaving young children most vulnerable to infection, 79.9% (<19 years) vs 89.1% (≥19 years). Interview questions on previous vaccinations did not correlate to serology.ConclusionRefugees have measles immunity slightly lower than the host population.     

Risk factors for measles virus infection and susceptibility in persons aged 15 years and older in China: A multi-site case-control study, 2012–2013

IntroductionEndemic measles persists in China, despite >95% reported coverage of two measles-containing vaccine doses and nationwide campaign that vaccinated >100 million children in 2010. An increasing proportion of infections now occur among adults and there is concern that persistent susceptibility in adults is an obstacle to measles elimination in China. We performed a case-control study in six Chinese provinces between January 2012 to June 2013 to identify risk factors for measles virus infection and susceptibility among adults.MethodsPersons ≥15 years old with laboratory-confirmed measles were age and neighborhood matched with three controls. Controls had blood specimens collected to determine their measles IgG serostatus. We interviewed case-patients and controls about potential risk factors for measles virus infection and susceptibility. Unadjusted and adjusted matched odds ratios and 95% confidence intervals (CIs) were calculated via conditional logistic regression. We calculated attributable fractions for infection for risk factors that could be interpreted as causal.Results899 cases and 2498 controls were enrolled. Among controls, 165 (6.6%) were seronegative for measles IgG indicating persistent susceptibility to infection. In multivariable analysis, hospital visit and travel outside the prefecture in the prior 1–3 weeks were significant risk factors for measles virus infection. Occupation and reluctance to accept measles vaccination were significant risk factors for measles susceptibility. The calculated attributable fraction of measles cases from hospital visitation was 28.6% (95% CI: 20.6–38.8%).ConclusionsExposure to a healthcare facility was the largest risk factor for measles virus infection in adults in China. Improved adherence to hospital infection control practices could reduce risk of ongoing measles virus transmission and increase the likelihood of achieving and sustaining measles elimination in China. The use of control groups stratified by serological status identified distinct risk factors for measles virus infection and susceptibility among adults.     

Young men who have sex with men’s awareness,acceptability, and willingness to participate in HIV vaccine trials: Results from a nationwide online pilot study

BackgroundNew cases of human immunodeficiency virus (HIV) among young men who have sex with men (YMSM) underscore the need to examine their willingness to use biomedical prevention methods, including an acceptable and efficacious HIV vaccine. We examined whether YMSM’s vaccine altruism and vaccine-related socials concerns factors were associated with HIV vaccine acceptability across two vaccine efficacy scenarios, and their awareness and willingness to participate in HIV vaccine research.MethodsThis secondary analysis uses data from a mHealth trial with YMSM at heightened HIV risk (N = 137; 50% racial/ethnic minority; M = 21.7 years). Most YMSM (91.2%) had tested for HIV, and 17.5% (N = 24) reported a prior STI. We used paired-samples t-test to compare differences in efficacy acceptability (50% vs 85%), followed by multivariable regressions examining whether vaccine attitudes (altruism and social concerns) were associated with vaccine acceptability and awareness and willingness to participate in HIV vaccine trials. We controlled for age, education, race/ethnicity, prior HIV testing, and STI diagnosis in our analyses.ResultsAcceptability for the HIV vaccine with 85% efficacy (M = 8.86; SD = 1.76) was greater than acceptability in the 50% efficacy scenario (M = 7.60; SD = 2.58). Altruistic attitudes were associated with greater vaccine acceptability at 50% (β = 0.62) and 85% (β = 0.59) efficacy. Higher educational attainment was negatively associated with a vaccine with 50% efficacy (β = −0.20, but not for 85% efficacy. Greater vaccine-related social concerns were negatively associated with HIV vaccine research awareness (AOR = 0.38 (95% CI: 0.22, 0.67). Willingness to participate in a HIV vaccine trial was positively associated with age (β = 0.18) and altruism (β = 0.60), and negatively associated with education (β = −0.21).ConclusionsYMSM find HIV vaccines as an acceptable prevention modality and are willing to participate in HIV vaccine trials. Findings highlight the need to consider YMSM's altruistic and social concerns attitudes in HIV vaccine research and explore how to leverage these attitudes in research campaigns.ClinicalTrials.gov Identifier: NCT02842060.     

MomsTalkShots: An individually tailored educational application for maternal and infant vaccines

IntroductionThe development and initial assessment in a clinical setting of a theory-driven, individually tailored educational application (app), MomsTalkShots, focused on increasing uptake of maternal and infant vaccines is described.MethodsMomsTalkShots algorithmically tailored videos based on parent needs to deliver an intervention that was specifically responsive to individual vaccine attitudes, beliefs and intentions, demographics, and source credibility. MomsTalkShots was evaluated among 1103 pregnant women recruited from 23 geographically and socio-demographically diverse obstetrician-gynecologist offices in Georgia and Colorado in 2017. Self-reported information needs were assessed pre-and post-videos and participants self-reported factors related to usability and analyzed in 2018.ResultsThe vast majority of women reported MomsTalkShots was helpful (95%), trustworthy (94%), interesting (97%) and clear to understand (99%), none of which varied by demographics or parity. Reported usability was slightly lower among vaccine hesitant women, yet the majority reported MomsTalkShots was helpful (91%), trustworthy (85%), interesting (97%) and clear (99%). The majority of women (72%) who did not have enough vaccine information pre-videos reported enough information post-videos.ConclusionsMomsTalkShots was designed to provide individually tailored vaccine information to pregnant women from a population with varied vaccine intentions, confidence and vaccine concerns. MomsTalkShots was extremely well-received among pregnant women, even among women who were initially vaccine hesitant and did not intend to vaccinate themselves and their infants according to the recommended immunization schedule. Next steps include evaluation to assess impact on vaccine uptake and expansion to adolescent and adult vaccines.     

Anal human papillomavirus infections in young unvaccinated men who have sex with men attending a sexual health clinic for HPV vaccination in Melbourne,Australia

The Victorian Government introduced a time-limited quadrivalent human papillomavirus (HPV) vaccination catch-up program targeting gay and bisexual men who have sex with men (MSM) aged up to 26 years in 2017. As of 2017, men aged ≥20 years were not eligible for the school-based HPV vaccination program. This study examined the prevalence of anal HPV among 496 MSM aged 20–26 years before they received the first dose of the HPV vaccine at the Melbourne Sexual Health Centre, Australia. More than half (56.5%) had any high-risk HPV genotypes detected in the anus. Almost half (43.1%) had at least one quadrivalent HPV vaccine-preventable genotype (6, 11, 16 or 18) and one-fifth (21.0%) had HPV 16 detected in the anus. These findings suggest that a targeted catch-up HPV vaccination program for MSM is still beneficial to protect against high-risk HPV genotypes associated with anal cancer, as well as low-risk HPV genotypes.     

Neospora caninum antigens displaying virus-like particles as a bivalent vaccine candidate against neosporosis

Neospora caninum is a causative and transmissible agent of dog and bovine neosporosis. The resulting reproductive failures in infected cattle lead to significant economic losses worldwide. However, there is no satisfactory treatment or vaccine currently available to combat this pathogen. Thus, the development of appropriate vaccines to manage its infection and transmission is urgently needed. In this study, we expressed Rous sarcoma virus-like particles (RSV-LP) that displayed dual N. caninum antigens in silkworms. The antigen candidates are modified by adding a transmembrane domain of GP64 protein from Bombyx mori nucleopolyhedrovirus (BmNPV) to the C-terminus of surface antigen 1 (NcSAG1) and SAG1-related sequence 2 (NcSRS2). The NcSRS2 alone or the NcSAG1/NcSRS2 bivalent form displaying RSV-LPs were purified using sucrose density gradient centrifugation. These purified VLPs were then used for immunizations in gerbils, Meriones unguiculatus, to evaluate the anti-N. caninum effects in vivo. The results demonstrated that antigens displaying RSV-LPs in immunized gerbils produced the antigen-specific antibody, leading to a relatively lower parasite load after infections of N. caninum. To the best of our knowledge, this is the first study to present an RSV-LP vaccine displaying bivalent antigens from neosporosis. Taken together, our strategy suggests that silkworm-expressed virus-like particles (VLPs) are promising bivalent vaccine candidates against N. caninum infections.     

Do Gender and Season Modify the Triggering Effect of Ambient Temperature on Ischemic Stroke?

BackgroundIschemic stroke (IS) is a multifactorial disorder, a leading cause of long-term disability, and the second most common cause of death. Previous studies have examined the association between stroke and weather conditions with conflicting results. In this study we aimed to investigate the association between changes in ambient temperature and risk of IS onset.MethodsWe used a time-stratified case-crossover study design including all patients admitted to Soroka University Medical Center in southern Israel between 2012 and 2014 for IS. Exposure windows of 6, 12, 24, 48, 72, and 96 hours were examined. All patients were assessed and classified by a neurologist. Temperature (°C), and relative humidity (%) were obtained from monitoring stations located in Beer-Sheva.ResultsA total of 1,174 patients visited Soroka University Medical Center for admission for an IS during the study period. Among them, 56% were male, on average 69.8 ± 13.1 years old. IS incidence was associated with increase in temperature during the summer and autumn season over the 96 hours preceding symptoms onset; the odds ratio (OR) for an increase of 5°C was 3.10 (95% CI, 1.45–6.61) during the summer and 1.86 (95% CI, 1.15–2.99) in autumn. The association between temperature and stroke onset during the winter was negative (OR, 0.68; 95% CI, 0.48–0.97) for 96-hour moving average temperature exposure. Men were more sensitive to 96-hour exposure window temperature fluctuations (OR, 1.35; 95% CI, 1.01–1.80) than women (OR, 0.96; 95% CI, 0.68–1.36). We did not find any associations between IS onset and differences between the maximum and minimum measurements of temperature.ConclusionsOur findings showed that short-term exposure to high temperatures is associated with a higher risk of IS in men but not in women. Further study is needed to validate this observation and to understand its pathophysiology.