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EMBO Molecular Medicine Jun 2024Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and...
Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.
Topics: Animals; Mice; Viral Vaccines; Micelles; Adjuvants, Vaccine; Adjuvants, Immunologic; Antibodies, Viral; Rabies virus; Dendritic Cells; Polymers; Female; Mice, Inbred C57BL; Influenza A virus; Mice, Inbred BALB C
PubMed: 38750307
DOI: 10.1038/s44321-024-00076-4 -
Journal of Veterinary Diagnostic... Jul 2024We performed a retrospective study of all case submissions for the rabies virus (RABV) direct fluorescent antibody test (DFAT) requested of the Tifton Veterinary...
We performed a retrospective study of all case submissions for the rabies virus (RABV) direct fluorescent antibody test (DFAT) requested of the Tifton Veterinary Diagnostic and Investigational Laboratory (Tifton, GA, USA) between July 2010 and June 2021. Submitted were 792 samples from 23 animal species from 89 counties in Georgia, and 4 neighboring counties in Florida, 1 in South Carolina, and 1 in Alabama. In 13 (1.6%) cases, the DFAT result was inconclusive; 779 (98.4%) cases had a conclusive (positive or negative) test result. Of these 779 cases, 79 (10.1%) tested positive across 10 species. The remaining 700 (89.9%) cases were negative. The main reason for submission for RABV testing was human exposure to a potentially rabid animal in 414 (52.3%) cases. Among the 79 positive cases, 74 (93.7%) involved wildlife; raccoons (51 cases; 68.9%) were the primary host confirmed with RABV infection, followed by skunk and fox (8 cases each; 10.8%), bobcat (5 cases; 6.8%), and bats (2 cases; 2.7%). Only 5 domestic animals (6.3% of the positive cases) tested positive during our study period; one from each of the bovine, canine, caprine, equine, and feline species. Hence, the sylvatic cycle plays the predominant role in circulating RABV infection in our study area.
Topics: Animals; Rabies; Retrospective Studies; Animals, Wild; Animals, Domestic; Rabies virus; Fluorescent Antibody Technique, Direct
PubMed: 38745456
DOI: 10.1177/10406387241247283 -
Methods in Molecular Biology (Clifton,... 2024Mononegaviruses are promising tools as oncolytic and transgene vectors for gene therapy and regenerative medicine. However, when mononegaviruses are used for therapeutic...
Mononegaviruses are promising tools as oncolytic and transgene vectors for gene therapy and regenerative medicine. However, when mononegaviruses are used for therapeutic applications, the viral activity must be strictly controlled due to concerns about toxicity and severe side effects. With this technology, mononegavirus vectors can be grown where they are intended and can be easily removed when they are no longer needed. In particular, a photoswitch protein called Magnet (consisting of two magnet domains) is incorporated into the hinge region between the connector and methyltransferase domains of the mononegavirus polymerase protein (L protein) to disrupt the L protein functions. Blue light (470 ± 20 nm) irradiation causes the dimerization of the two magnet domains, and the L protein is restored to activity, allowing viral gene expression and virus replication. Since the magnet domains' dimerization is reversible, viral gene expression and replication cease when blue light irradiation is stopped.
Topics: Virus Replication; Gene Expression Regulation, Viral; Humans; Viral Proteins; Light; Animals; Genetic Vectors
PubMed: 38743361
DOI: 10.1007/978-1-0716-3870-5_4 -
Antiviral Research Jul 2024The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the...
The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.
Topics: Animals; Rabies virus; COVID-19 Vaccines; Mice; SARS-CoV-2; COVID-19; Antibodies, Viral; Spike Glycoprotein, Coronavirus; Mice, Inbred BALB C; Antibodies, Neutralizing; Female; Humans; Immunity, Humoral; Genetic Vectors; Vaccine Efficacy; Vaccines, Synthetic
PubMed: 38740191
DOI: 10.1016/j.antiviral.2024.105905 -
International Journal of Molecular... Apr 2024Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM...
Tripartite motif (TRIM) proteins are a multifunctional E3 ubiquitin ligase family that participates in various cellular processes. Recent studies have shown that TRIM proteins play important roles in regulating host-virus interactions through specific pathways, but their involvement in response to rabies virus (RABV) infection remains poorly understood. Here, we identified that several TRIM proteins are upregulated in mouse neuroblastoma cells (NA) after infection with the rabies virus using RNA-seq sequencing. Among them, TRIM44 was found to regulate RABV replication. This is supported by the observations that downregulation of TRIM44 inhibits RABV replication, while overexpression of TRIM44 promotes RABV replication. Mechanistically, TRIM44-induced RABV replication is brought about by activating autophagy, as inhibition of autophagy with 3-MA attenuates TRIM44-induced RABV replication. Additionally, we found that inhibition of autophagy with rapamycin reverses the TRIM44-knockdown-induced decrease in LC3B expression and autophagosome formation as well as RABV replication. The results suggest that TRIM44 promotes RABV replication by an autophagy-dependent mechanism. Our work identifies TRIM44 as a key host factor for RABV replication, and targeting TRIM44 expression may represent an effective therapeutic strategy.
Topics: Animals; Humans; Mice; Autophagy; Cell Line, Tumor; Host-Pathogen Interactions; Intracellular Signaling Peptides and Proteins; Rabies; Rabies virus; Tripartite Motif Proteins; Virus Replication
PubMed: 38731834
DOI: 10.3390/ijms25094616 -
PloS One 2024Rabies virus (RABV; species Lyssavirus rabies) is causing one of the oldest zoonotic diseases known to mankind, leading to fatal encephalomyelitis in animals and humans....
BACKGROUND
Rabies virus (RABV; species Lyssavirus rabies) is causing one of the oldest zoonotic diseases known to mankind, leading to fatal encephalomyelitis in animals and humans. Despite the existence of safe and effective vaccines to prevent the disease, an estimated 99% of human rabies deaths worldwide are caused by dog-mediated rabies with children at the highest risk of infection. Rabies has been endemic in Madagascar for over a century, yet there has been little research evaluating local knowledge and practices impacting on the rabies control and prevention. Thus, this study was undertaken to better understand the dog ecology including canine vaccine coverage and to assess knowledge and practices of dog owners and veterinarians.
METHODOLOGY
A cross-sectional study was conducted among 123 dog-owning households in thirteen fokontanys in Mahajanga from July 4 to September 13, 2016. Single and multi-member dog-owning households in the study area on the day of the interview were eligible for inclusion and purposively selected with the support of a local guide. The survey included a household questionnaire capturing information on the dog's demographics, husbandry practices, knowledge and practices towards rabies and its control measures; the dog ecology questionnaire collected dog characteristics, vaccination status and husbandry practices. All households that reported a dog bite incident, were invited to participate in a dog bite questionnaire. In addition, direct observations of roaming dogs were conducted to assess dog population demographics and to document behavioural characteristics. Two veterinarians were purposively selected and took part in an interview during the survey period, providing information on rabies control activities, including dog-care practices in the area. Descriptive and inferential data analyses were performed using Epi Info version 7.1.5.0 (CDC Atlanta, USA).
RESULTS
We recorded a total of 400 dogs, of which 338 (84.5%) were owned amongst 123 households. More than half (67.8%) of owned dogs were between 1 to 5 years old and 95.6% were kept for guarding purposes. 45% of the surveyed dogs had free access to roam outside the premises. The majority (85.4%) of dog owners were knowledgeable that a dog bite could potentially transmit RABV to humans. 19 dog bites were reported and of these 73.6% were caused by the owner's or a neighbour's dog. In 6 of the 19 cases, children between 7 and 15 years of age were the victims. Dog vaccination coverage against rabies was 34% among owned dogs. Of the participants aware of a veterinarian, the majority (55/82) indicated that they accessed veterinarian services at irregular intervals. The main obstacles to vaccinations cited by dog owners were limited financial resources and difficulty accessing veterinary care.
CONCLUSION
This study contributes to enhanced understanding of the dog ecology including canine vaccine coverage as well as knowledge and practices of dog owners in Madagascar. Most dogs in the study area were accessible for preventive vaccination through their owners, however only one third of the investigated canine population was vaccinated against rabies. Concerted national efforts towards rabies prevention and control should aim to address financial challenges and access to veterinary services.
Topics: Dogs; Animals; Rabies; Madagascar; Dog Diseases; Humans; Rabies Vaccines; Cross-Sectional Studies; Male; Female; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; Adult; Vaccination Coverage; Middle Aged; Ecology; Rabies virus
PubMed: 38722982
DOI: 10.1371/journal.pone.0302690 -
PLoS Neglected Tropical Diseases May 2024
PubMed: 38722845
DOI: 10.1371/journal.pntd.0012171 -
IDCases 2024Rabies is a zoonosis caused by viruses of the family Rhabdoviridae. Prophylaxis with the rabies vaccine and immunoglobulins, depending on the severity of the case, is...
INTRODUCTION
Rabies is a zoonosis caused by viruses of the family Rhabdoviridae. Prophylaxis with the rabies vaccine and immunoglobulins, depending on the severity of the case, is recommended. After vaccination, mild, moderate, or severe adverse events (AE) are described. Although rare, severe skin reactions may occur, increasing the risk of anaphylaxis.
CASE REPORT
An 84-year-old woman was attacked by a stray unknown cat, leaving her with bites and scratches in the neck region and multiple injuries. The case was classified as severe. About 3 h after the first dose of the rabies vaccine, disseminated purplish spots appeared on her lower limbs, worsening significantly after the second dose, requiring hospitalization for the application of the third dose under observation, dermatology evaluation, and collection of skin tissue for biopsy. She was discharged 24 h after the third vaccination, and the purple spots cleared gradually. The biopsy suggested an adverse reaction to the vaccine components. Immunohistochemistry of the rabies virus antigen in dermal nerve fillets was negative. The seroconversion post rabies vaccine showed IgG antibody values below the reference levels.
CONCLUSION
Vaccination against rabies is extremely important; however, AEs may occur. Our patient developed an important AE and required hospitalization. After complete vaccination, the serum was not converted. A similar case was not previously described, and the case report is important for the creation of jurisprudence on rabies vaccination in elderly patients in Brazil.
PubMed: 38721055
DOI: 10.1016/j.idcr.2024.e01974 -
Journal of Virological Methods Jun 2024Rabies, a fatal zoonotic viral disease affecting mammals, including humans, remains a significant global health concern, particularly in low-income countries. The...
Rabies, a fatal zoonotic viral disease affecting mammals, including humans, remains a significant global health concern, particularly in low-income countries. The disease, primarily transmitted through infected animal saliva, prompts urgent diagnosis for timely post-exposure prophylaxis (PEP). The gold standard diagnostic test, direct fluorescent antibody test (dFAT), while sensitive, suffers from limitations such as subjective interpretation and high costs. As a confirmatory technique, the LN34 Pan-Lyssavirus RT-qPCR assay has emerged as a promising tool for universal Lyssavirus detection. This study evaluated its performance using 130 rabies virus isolates representing eleven Brazilian variants and 303 clinical samples from surveillance operations. The LN34 assay demonstrated 100% sensitivity and 98% specificity compared to dFAT. Additionally, it detected all samples, including those missed by dFAT, indicating superior sensitivity. The assay's specificity was confirmed through Sanger nucleotide sequencing, with only a minimal false-positive rate. Comparative analysis revealed higher accuracy and concordance with dFAT than traditional rabies tissue culture infection tests (RTCIT). False-negative RTCIT results were attributed to low viral load or suboptimal sampling. These findings underscore the LN34 assay's utility as a confirmatory technique, enhancing rabies surveillance and control in Brazil. Its widespread adoption could significantly improve diagnostic sensitivity, crucial for effective PEP and public health interventions.
Topics: Rabies; Brazil; Sensitivity and Specificity; Rabies virus; Humans; Animals; Real-Time Polymerase Chain Reaction; Lyssavirus; RNA, Viral; Viral Load
PubMed: 38718900
DOI: 10.1016/j.jviromet.2024.114948 -
Emerging Microbes & Infections Dec 2024Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade...
Monkeypox virus (MPXV) is a re-emerging zoonotic poxvirus responsible for producing skin lesions in humans. Endemic in sub-Saharan Africa, the 2022 outbreak with a clade IIb strain has resulted in ongoing sustained transmission of the virus worldwide. MPXV has a relatively wide host range, with infections reported in rodent and non-human primate species. However, the susceptibility of many domestic livestock species remains unknown. Here, we report on a susceptibility/transmission study in domestic pigs that were experimentally inoculated with a 2022 MPXV clade IIb isolate or served as sentinel contact control animals. Several principal-infected and sentinel contact control pigs developed minor lesions near the lips and nose starting at 12 through 18 days post-challenge (DPC). No virus was isolated and no viral DNA was detected from the lesions; however, MPXV antigen was detected by IHC in tissue from a pustule of a principal infected pig. Viral DNA and infectious virus were detected in nasal and oral swabs up to 14 DPC, with peak titers observed at 7 DPC. Viral DNA was also detected in nasal tissues or skin collected from two principal-infected animals at 7 DPC post-mortem. Furthermore, all principal-infected and sentinel control animals enrolled in the study seroconverted. In conclusion, we provide the first evidence that domestic pigs are susceptible to experimental MPXV infection and can transmit the virus to contact animals.
Topics: Animals; Monkeypox virus; Swine; Mpox (monkeypox); Swine Diseases; DNA, Viral; Antibodies, Viral; Humans; Skin; Nose
PubMed: 38712637
DOI: 10.1080/22221751.2024.2352434