The Durability of Vaccine Efficacy against Ocular HSV-1 Infection Using ICP0 Mutants 0∆NLS and 0∆RING Is Lost over Time

Vaccines to viral pathogens in experimental animal models are often deemed successful if immunization enhances resistance of the host to virus challenge as measured by cumulative survival, reduction in virus replication and spread and/or lessen or eliminate overt tissue pathology. Furthermore, the duration of the protective response against challenge is another important consideration that drives a vaccination regimen. In the current study, we assessed the durability of two related vaccines, 0∆NLS and 0∆RING, against ocular herpes simplex virus type 1 (HSV-1) challenge in mice thirty days (short-term) and one year (long-term) following the vaccine boost. The short-term vaccine efficacy study found the 0∆RING vaccine to be nearly equivalent to the 0∆NLS vaccine in comparison to vehicle-vaccinated mice in terms of controlling virus replication and preserving the visual axis. By comparison, the long-term assessment of the two vaccines found notable differences and less efficacy overall as noted below. Specifically, the results show that in comparison to vehicle-vaccinated mice, the 0∆NLS and 0∆RING vaccinated groups were more resistant in terms of survival and virus shedding following ocular challenge. Moreover, 0∆NLS vaccinated mice also possessed significantly less infectious virus in the peripheral and central nervous systems but not the cornea compared to mice vaccinated with vehicle or 0∆RING which had similar levels. However, all vaccinated groups showed similar levels of blood and lymphatic vessel genesis into the central cornea 30 days post infection. Likewise, corneal opacity was also similar among all groups of vaccinated mice following infection. Functionally, the blink response and visual acuity were 25–50% lower in vaccinated mice 30 days post infection compared to measurements taken prior to infection. The results demonstrate a dichotomy between resistance to infection and functional performance of the visual axis that collectively show an overall loss in vaccine efficacy long-term in comparison to short-term studies in a conventional prime-boost protocol.

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Evaluation of a quadrivalent inactivated vaccine for the protection of cattle against diseases due to common viral infections : research report

Journal of the South African Veterinary Association ◽

10.4102/jsava.v75i3.469 ◽

2004 ◽

Vol 75 (3) ◽

Cited By ~ 6

Author(s):

J.R. Patel

Keyword(s):

Quadrivalent Vaccine ◽

Research Report ◽

Control Group ◽

Short Term ◽

Challenge Virus ◽

Virus Shedding ◽

Virus Challenge ◽

Diarrhoea Virus ◽

Syncytial Virus

Efficacy of an inactivated quadrivalent vaccine containing infectious bovine rhinotracheitis (IBR) virus, parainfluenza type 3 (PI3) virus, bovine virus diarrhoea virus (BVDV) and bovine respiratory syncytial virus (BRSV) was assessed in naive bovine calves to evaluate short-term (4-18 weeks) and long-term (24-38 weeks) protection following the basic intramuscular vaccination regime of 2 inoculations a month apart. Vaccination was staggered between the long-term and the short-term groups by about 5 months so that both groups, along with a matched group of 6 unvaccinated (control) calves, could be challenged at the same time. Sequential challenges at intervals of 3-8 weeks were done in the order: IBR virus (intranasally, IN), PI3 virus (IN and intratracheally, IT), pestiviruses (IN) and BRSV (IN and IT). The IBR virus challenge produced febrile rhinotracheitis (FRT) in control calves but both the severity and the duration of FRT was significantly reduced in both vaccinated groups. The amount and the duration of IBR virus shed by the vaccinated groups was significantly reduced compared to the control group. Although PI3 virus, pooled pestivirus and BRSV challenges did not result in a noteworthy disease, challenge virus shedding (amount and duration) from the upper (all 3 viruses) and the lower (BRSV) respiratory tracts was significantly reduced in vaccinated groups. After pestivirus challenge, sera and leukocytes from all control calves were infectious for 6-9 days whereas virus was recovered only from leukocytes in vaccinated calves and only for 1.6-2.7 days. Thus a standard course of the quadrivalent vaccine afforded a significant protection against IBR virus, PI3 virus, BVDV and BRSV for at least 6 months.

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The Effects of Delayed-Onset Chemotherapy using Famciclovir or Valaciclovir in a Murine Immunosuppression Model for HSV-1

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632029500600402 ◽

1995 ◽

Vol 6 (4) ◽

pp. 210-216 ◽

Cited By ~ 20

Author(s):

H. J. Field ◽

A. M. Thackray

Keyword(s):

Virus Replication ◽

Post Infection ◽

Cell Function ◽

Clinical Signs ◽

Cellular Level ◽

High Titre ◽

Beneficial Effects ◽

The Central Nervous System ◽

Uninoculated Control ◽

Hsv 1

BALB/c mice were immunosuppressed using a dosing regimen of cyclosporin-A previously shown to interfere with T-cell function. HSV-1 was then inoculated into the skin of the ear pinna and the infection allowed to progress for 5 days. In untreated mice, virus replication was observed in both ear tissue and the central nervous system (brainstem). Virus replication continued at high titre in both sites for 15 days, the duration of the experiment. This model was used to investigate the efficacy of famciclovir (FCV) and vaiaciclovir (VACV), which are the oral prodrugs of penciclovir and acyclovir, respectively, on an established HSV-1 infection. Mice were treated orally with either FCV or VACV at 50 mg kg−1, from day 5 to day 10 post-infection. Within 2 days of the onset of therapy, virus titres in both skin and neural tissues were reduced significantly, and by day 10 post-infection less than 101 p.f.u. per tissue was detectable compared with approximately 104 p.f.u. in the untreated control mice. However, when VACV therapy was stopped, there was a recurrence of infectious virus replication within the ear pinna and the brainstem 2 days later. No recurrence of virus replication was observed in mice that had been treated with FCV. In addition, FCV treatment was superior to VACV at reducing the incidence of clinical signs and disease. Furthermore, mice receiving FCV gained weight more quickly than infected controls and reached uninoculated control weights by the end of the study period. In contrast, VACV had no such beneficial effects. These results confirm that VACV and FCV have different effects on the pathogenesis of HSV. The reasons for this appear to result from critical differences in the mechanism of action of the two compounds at a cellular level. We suggest that these data have important implications for the treatment of severe herpesvirus infections in man.

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Evaluation of classical swine fever E2 (CSF-E2) subunit vaccine efficacy in the prevention of virus transmission and its potential application for virus eradication in field farms

10.21203/rs.3.rs-97837/v1 ◽

2020 ◽

Author(s):

Jing-Yuan Chen ◽

Chi-Ming Wu ◽

Zeng-Weng Chen ◽

Chih-Ming Liao ◽

Ming-Chung Deng ◽

...

Keyword(s):

Vaccine Efficacy ◽

Subunit Vaccine ◽

Clinical Symptoms ◽

Horizontal Transmission ◽

Classical Swine Fever ◽

Early Application ◽

Virus Eradication ◽

Virus Shedding ◽

The Impact

Abstract Background: Classical swine fever (CSF) is one of the most devastating pig diseases that affect the swine industry worldwide. Besides stamping out policy for eradication, immunization with vaccines of live attenuated CSF or the CSF-E2 subunit is an efficacious measure of disease control. However, after decades of efforts, it is still hard to eliminate CSF from endemically affected regions and reemerging areas. Most of previous studies demonstrated the efficacy of different CSF vaccines in laboratories under high containment conditions, which may not represent the practical performance in field farms. The inadequate vaccine efficacy induced by unrestrained factors may lead to chronic or persistent CSF infection in animals that develop a major source for virus shedding among pig populations. In this study, a vaccination-challenge-cohabitation trial on specific-pathogen-free (SPF) pigs and long-term monitoring of sows and piglets were used to evaluate the efficacy and the impact of maternally derived antibody (MDA) interference on CSF vaccines in farm applications.Results: The trials demonstrated higher neutralizing antibody (NA) titers with no clinical symptoms and significant pathological changes in the CSF-E2 subunit vaccine immunized group after CSFV challenge. Additionally, none of the sentinel pigs were infected during cohabitation indicating that the CSF-E2 subunit vaccine could provoke adequate acquired immunity to prevent horizontal transmission. In field farm applications, the CSF-E2 subunit vaccine significantly reduced CSF viral RNA detection via saliva monitoring in a sow population that was routinely immunized with live attenuated CSF vaccine long term. Moreover, no adverse effects and an average of higher, long-lasting and consistent NA level could be detected in sows immunized with CSF-E2 subunit vaccine before parturition. Furthermore, early application of the CSF-E2 subunit vaccine in 3-week-old piglets illustrated no MDA interference on primary immunization whereas interference of MDA was noted in piglets vaccinated with live attenuated CSF.Conclusions: The CSF-E2 subunit vaccine demonstrated more flexibility and efficacy for immunization in both pregnant sows and piglets. These advantages could provide a novel approach to avoid possible virus shedding in sow population and MDA interference in piglets for control of CSF in field farm applications.

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Impact of Candida auris infection in a neutropenic murine model

10.1101/731281 ◽

2019 ◽

Author(s):

Steven R. Torres ◽

Amber Pichowicz ◽

Fernando Torres-Velez ◽

Renjie Song ◽

Navjot Singh ◽

...

Keyword(s):

Post Infection ◽

Bloodstream Infections ◽

Global Public Health ◽

Short Term ◽

Candida Auris ◽

Infected Control ◽

Target Organs ◽

Head Bobbing ◽

Neutrophil Depletion

AbstractCandida auris has become a global public health threat due to its multidrug resistance and persistence in hospital and nursing home settings. Although a skin colonizer, C. auris can cause fatal bloodstream infections and most patients succumb to multi-organ failure. Currently, there are limited animal models to study the progression of C. auris infection. Here we compare two murine models of neutrophil depletion using monoclonal antibodies 1A8, anti-Ly6G+ and RB6-8C5 anti-Ly6G+-Ly6C+. We also compare inoculums of 107 and 108 as well as the intravenous and gavage routes of infection. The results reveal that neutrophil depletion in BALB/c mice is sustained long-term with the 1A8 antibody and short-term with RB6-8C5. Target organs were kidney, heart and brain as these had the highest organ fungal burden in neutrophil depleted and to some extent in infected control mice. We found that C. auris is shed in urine and feces for neutrophil depleted mice. The gavage model is not an ideal route as dissemination was not detected. Eight days post C. auris infection all surviving mice display a unique behavioral phenotype characterized by torticollis and tail spin that progresses to head bobbing and body curling like phenotype by day 22, that continues to persist even 104 days post infection. Lastly, we found C. auris remains in tissues of infected control mice, 34 plus days post infection suggesting that C. auris stays present in the host without causing disease but becomes opportunistic upon a change in the hosts immune status such as neutrophil depletion.

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Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

Behavioral and Brain Sciences ◽

10.1017/s0140525x15000928 ◽

2016 ◽

Vol 39 ◽

Author(s):

Mary C. Potter

Keyword(s):

Working Memory ◽

Rapid Serial Visual Presentation ◽

Language Comprehension ◽

Short Term Memory ◽

Visual Presentation ◽

Long Term Memory ◽

Short Term ◽

Term Memory ◽

Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

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Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159412 ◽

1990 ◽

Vol 48 (3) ◽

pp. 374-375

Author(s):

D.E. Loudy ◽

J. Sprinkle-Cavallo ◽

J.T. Yarrington ◽

F.Y. Thompson ◽

J.P. Gibson

Keyword(s):

Antidepressant Drug ◽

Beagle Dogs ◽

Long Term Effects ◽

Short Term ◽

Platelet Counts ◽

Toxicological Studies ◽

Induced Aggregation ◽

Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

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Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

American Journal of Audiology ◽

10.1044/2020_aja-20-00018 ◽

2020 ◽

Vol 29 (4) ◽

pp. 710-727

Author(s):

Beula M. Magimairaj ◽

Naveen K. Nagaraj ◽

Alexander V. Sergeev ◽

Natalie J. Benafield

Keyword(s):

Auditory Processing ◽

Short Term Memory ◽

Group Differences ◽

Long Term Memory ◽

Short Term ◽

Significant Group ◽

Term Memory ◽

Memory And Attention ◽

Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

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