Recombinant DNA technology for producing new rinderpest virus vaccines

Goal of vaccination is to control rather than suspension or abolition disease with few exceptions. In the 1970s, smallpox & two other human diseases like polio and measles were being targeted for eradication by the World Health Organization. Cattle plague caused by rinderpest virus, has put this virus on the verge of global extinction. In Europe, Asia and Africa, for decade, cattle plague disease affected by this virus. The favorable outcome of the Global Rinderpest Eradication Program by vaccination was to change people's lives economically and socially. In this article, researcher illustrated about the history of the development of this vaccine and the new research to produce marker vaccines by recombinant DNA technology and reverse genetics. Furthermore, researcher gave a configuration that marker vaccines can make a valuable contribution in the final stages of the rinderpest eradication program.

(RA)

Canine Distemper Virus Infection in the Free-Living Wild Canines, the Red Fox (Vulpes vulpes) and Jackal (Canis aureus moreoticus), in Croatia

Canine distemper virus (CDV) is a single stranded negative-sense RNA virus, morbillivirus usually affecting carnivores. The disease is highly contagious, posing a threat to both wild and domestic canids. Like other members of the family Paramyxoviridae, the virus encodes six proteins: nucleocapsid, phospho-, matrix, fusion, hemagglutinin and polymerase proteins. This study investigated the prevalence of this disease in Croatia, in which 176 red foxes and 24 jackal brain samples were collected during a Rabies surveillance in 2021-2022. Only four red foxes (2.27%) tested positive using real-time RT-PCR. All the jackals tested negative for the canine distemper. The CDVs confirmed here belong to the Europa 1 genotype; genetically similar to the CDV sequences obtained from Croatian, Italian and German red foxes, and German barger, Hungarian polecats and Hungarian and German dogs.

(WWN)

GDP polyribonucleotidyltransferase domain of vesicular stomatitis virus polymerase regulates leader-promoter escape and polyadenylation-coupled termination during stop-start transcription

 The unconventional mRNA capping enzyme, the GDP polyribonucleotidyltransferase (PRNTase) domain within the vesicular stomatitis virus (VSV) L protein, possesses a crucial "priming-capping loop." This loop governs both the initiation of leader RNA synthesis and the capping of monocistronic mRNAs during VSV's unique stop-start transcription cycle. The authors’ investigation focused on specific basic amino acid residues within a helix structure directly linked to this loop. Through identifying single-point mutations, they unveiled previously undocumented defective traits in various stages of stop-start transcription. Mutations at residue R1183 (R1183A and R1183K) notably decreased leader RNA synthesis by impeding early elongation, but not de novo initiation or productive elongation. Conversely, mutations at residue R1178 (R1178A and R1178K) reduced the efficiency of mRNA synthesis termination at gene junctions, leading to increased abnormal polycistronic mRNA levels. Remarkably, both residues R1183 and R1178 were found to be nonessential for cap-forming activities. The lethal impact of the R1183K mutation on VSV contrasted with the attenuation caused by the R1178K mutation, which generated polycistronic mRNAs during infection. These findings underscore the multifaceted role of the PRNTase domain, extending beyond pre-mRNA capping, in ensuring precise stop-start transcription in VSV. 

(LA)

Recombinant vesicular stomatitis virus-vectored vaccine induces long-lasting immunity against Nipah virus disease

Novel henipavirus, Langya virus got worldwide concern after infecting over three dozen people in China. Henipaviruses as respiratory pathogen could trace another pandemic like deadly Nipah Virus (NiV). It produces highly fatal respiratory disease & encephalitis in humans in Bangladesh & India. No authorized remedy exists against NiV. Only ideal NiV vaccine would award to both fast-acting & long-lived protection. Researcher reported that a recombinant vesicular stomatitis virus-based (rVSV-based) vaccine expressing the NiV glycoprotein (rVSV-ΔG-NiVBG) that protected 100% NiV-associated lethality in nonhuman primates within a week. Objective of research is to assess the longevity of rVSV-ΔG-NiVBG. Researchers vaccinated African green monkeys (AGMs) in one year before challenging with a lethal dose of NiV. All vaccinated AGMs (whether receiving a single dose or prime-boosted) survived with no detectable clinical signs or NiV replication by producing humoral responses. Transcriptomic analyses showed that sign of adaptive immune correspond with vaccine-mediated protection. While vaccines for COVID-19 have given a durable protection, the research results suggest that rVSV-ΔG-NiVBG bring out a long-lasting immunity.

(AR)

An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs

As a member of the family Rhabroviridae, Rabies virus is a fatal zoonotic disease concentrated in developing countries of Africa and Asia. The disease is primarily transmitted to humans through bites of infected dogs; in which case the mortality is almost 100% once the clinical signs present. Inactivated Rabies vaccine is the conventional prophylactic method against Rabies. However, the modern technology has led to development of an mRNA vaccine (LVRNA001) whose efficacy was evaluated using mice and dogs. In the immunization and viral challenge experiment, the mice and dogs were injected intramuscularly with either inactive vaccine Rabvac® or LVRNA001. Virus was injected 14 and 35 days postimmunization for mice and dogs respectively. Blood samples were later taken for neutralization antibody test. In this study, the LVRNA001vaccine proved protective against Rabies virus. In the post-exposure immunization experiment, dogs were injected with 50-fold LD50 of virulent RABV-BD06. The dogs were then subjected to either the inactivated vaccine or LVRNA001 six hours later. Results indicate that dogs that received two 25 μg doses of LVRNA001 had 100% survival rate versus 33.33% that received inactivated vaccine. These results show that mRNA vaccine LVRNA001 offers more prophylaxis against Rabies compared to the inactive vaccine Rabvac®.

(WWN)

Reduced Nucleoprotein Availability Impairs Negative-Sense RNA Virus Replication and Promotes Host Recognition

Negative-sense RNA viruses (NSVs) utilize RNA-dependent RNA polymerases (RdRp) and nucleoproteins (NPs) to replicate their genome and transcribe mRNAs. These components form viral ribonucleoprotein complexes that play a crucial role in maintaining viral genetic material. A study investigated the impact of reduced NP levels in influenza A virus and Sendai virus through the manipulation of host microRNA expression. The results revealed that decreased NP levels not only led to a significant reduction in genome replication, but also triggered a heightened host antiviral response. Insufficient NP hindered the replication machinery of NSVs from processing full-length genomes, generating abnormal replication products that triggered host immune responses. This response was facilitated by the recognition by pathogen-associated molecular patterns, resulting in a robust host antiviral defense. Interestingly, the effects of limiting NP levels were consistent across various NSVs, including Ebola virus, Lassa virus, and measles virus. This study sheds light on the delicate balance that NSVs must strike between efficient replication and avoiding host immune responses. The findings offer insights into viral genome replication mechanisms and suggest potential avenues for developing effective antiviral strategies, adjuvants, and live-attenuated vaccines. 

(LA)