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Microbiology Spectrum Feb 2022Hepatitis-hydropericardium syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in huge economic losses to the poultry...
Hepatitis-hydropericardium syndrome (HHS) caused by the highly pathogenic fowl adenovirus serotype 4 (FAdV-4) has resulted in huge economic losses to the poultry industry globally. The gene, as a major virulence determiner, is also an important vaccine target against FAdV-4. In this study, we used a CRISPR/Cas9-based homology-dependent recombinant technique to replace the gene with and generate a novel recombinant virus, designated FAdV4-EGFP-rF2. Although FAdV4-EGFP-rF2 showed low replication ability compared to the wild-type FAdV-4 in LMH cells, FAdV4-EGFP-rF2 could effectively replicate in LMH-F2 cells with the expression of Fiber-2. Moreover, FAdV4-EGFP-rF2 was not only highly attenuated in chickens, but also could provide efficient protection against a lethal challenge of FAdV-4. Moreover, FAdV4-EGFP-rF2 without could induce neutralizing antibodies at the same level as FA4-EGFP with . These results clearly demonstrate that although affects the viral replication and pathogenesis of FAdV-4, it is not necessary for virus replication and induction of neutralizing antibodies; these findings provide novel insights into the roles of and highlight as an insertion site for generating live-attenuated FAdV-4 vaccines against FAdV-4 and other pathogens. Among all serotypes of fowl adenovirus, serotypes FAdV-1, FAdV-4, and FAdV-10 are unique members with two genes ( and ). Recent studies reveal that Fiber-1, not Fiber-2, directly triggers viral infection of FAdV-4, whereas Fiber-2, but not Fiber-1, has been identified as the major virulence determiner and an efficient protective immunogen for subunit vaccines. Here, we replaced with to generate a novel recombinant virus, designated FAdV4-EGFP-rF2. and studies on FAdV4-EGFP-rF2 revealed that was not necessary for either virus replication or efficient protection for FAdV-4; these results not only provide a novel live-attenuated vaccine candidate against HHS, but also give new ideas for generating a FAdV-4 based vaccine vector against other pathogens.
Topics: Adenoviridae Infections; Animals; Antibodies, Neutralizing; Antibodies, Viral; Aviadenovirus; Chickens; Poultry Diseases; Vaccines, Attenuated; Viral Proteins; Viral Vaccines
PubMed: 35107364
DOI: 10.1128/spectrum.01436-21 -
Clinical Infectious Diseases : An... Mar 2020The effectiveness of the live-attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% to 50%. The reasons for these discrepancies remain largely unclear.
BACKGROUND
The effectiveness of the live-attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% to 50%. The reasons for these discrepancies remain largely unclear.
METHODS
We use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The models incorporate 3 key antigenic distances: the distances between the vaccine strain, pre-existing immunity, and the challenge strain.
RESULTS
Our models show that an LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity than the circulating strain. The models also suggest 2 regimes in which LAIV that is matched to circulating strains may be protective: in children before they have built immunity to circulating strains and in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. We provide an explanation for the variation in vaccine effectiveness between studies and countries of vaccine effectiveness observed during the 2014-2015 influenza season.
CONCLUSIONS
LAIV is offered to children across the world; however, its effectiveness significantly varies between studies. Here, we propose a mechanistic explanation to understand these differences. We further propose a way to select the LAIV strain that would have a higher chance of being protective.
Topics: Child; Humans; Influenza Vaccines; Influenza, Human; Vaccines, Attenuated
PubMed: 31056675
DOI: 10.1093/cid/ciz358 -
Virology Journal May 2023Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of...
BACKGROUND
Pseudorabies (PR) (also called Aujeszky's disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections.
METHODS
The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines.
RESULTS
Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90-100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits.
CONCLUSIONS
The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.
Topics: Rabbits; Animals; Swine; Herpesvirus 1, Suid; Vaccines, Attenuated; Vaccines, Subunit; Pseudorabies; Adjuvants, Immunologic; GB virus C
PubMed: 37221518
DOI: 10.1186/s12985-023-02051-w -
Frontiers in Immunology 2022Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination... (Review)
Review
Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination stimulates diverse immune responses by mimicking natural infection. Induction of pathogen-specific antibodies or cell-mediated cytotoxicity provides means of specific protection, but LAV can also elicit unintended off-target effects, termed non-specific effects. Such mechanisms as short-lived genetic interference and non-specific innate immune response or long-lasting trained immunity and heterologous immunity allow LAVs to develop resistance to subsequent microbial infections. Based on their safety and potential for interference, LAVs may be considered as an alternative for immediate mitigation and control of unexpected pandemic outbreaks before pathogen-specific therapeutic and prophylactic measures are deployed.
Topics: Immunity; Immunity, Heterologous; Vaccination; Vaccines, Attenuated
PubMed: 35651619
DOI: 10.3389/fimmu.2022.877845 -
Frontiers in Cellular and Infection... 2024Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic... (Review)
Review
Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control.
Topics: Animals; Swine; Humans; Influenza Vaccines; Influenza, Human; Orthomyxoviridae Infections; Influenza A virus; Vaccines, Attenuated; Swine Diseases; Antibodies, Viral
PubMed: 38633745
DOI: 10.3389/fcimb.2024.1336013 -
Journal of Virology Dec 2023Coronaviruses are important pathogens of humans and animals, and vaccine developments against them are imperative. Due to the ability to induce broad and prolonged...
Coronaviruses are important pathogens of humans and animals, and vaccine developments against them are imperative. Due to the ability to induce broad and prolonged protective immunity and the convenient administration routes, live attenuated vaccines (LAVs) are promising arms for controlling the deadly coronavirus infections. However, potential recombination events between vaccine and field strains raise a safety concern for LAVs. The porcine epidemic diarrhea virus (PEDV) remodeled TRS (RMT) mutant generated in this study replicated efficiently in both cell culture and in pigs and retained protective immunogenicity against PEDV challenge in pigs. Furthermore, the RMT PEDV was resistant to recombination and genetically stable. Therefore, RMT PEDV can be further optimized as a backbone for the development of safe LAVs.
Topics: Animals; Coronavirus Infections; Porcine epidemic diarrhea virus; Recombination, Genetic; Swine; Swine Diseases; Vaccines, Attenuated; Viral Vaccines; Virus Replication; Cells, Cultured; Mutation
PubMed: 37971221
DOI: 10.1128/jvi.01193-23 -
Journal of Virology Oct 2023African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial...
Development of a new effective African swine fever virus vaccine candidate by deletion of the H240R and MGF505-7R genes results in protective immunity against the Eurasia strain.
African swine fever (ASF) caused by ASF virus (ASFV) is a highly contagious and acute hemorrhagic viral disease in domestic pigs. Until now, no effective commercial vaccine and antiviral drugs are available for ASF control. Here, we generated a new live-attenuated vaccine candidate (ASFV-ΔH240R-Δ7R) by deleting H240R and MGF505-7R genes from the highly pathogenic ASFV HLJ/18 genome. Piglets immunized with ASFV-ΔH240R-Δ7R were safe without any ASF-related signs and produced specific antibodies against p30. Challenged with a virulent ASFV HLJ/18, the piglets immunized with high-dose group (105 HAD50) exhibited 100% protection without clinical symptoms, showing that low levels of virus replication with no observed pathogenicity by postmortem and histological analysis. Overall, our results provided a new strategy by designing live-attenuated vaccine candidate, resulting in protection against ASFV infection.
Topics: Animals; African Swine Fever; African Swine Fever Virus; Sus scrofa; Vaccines, Attenuated; Viral Proteins; Viral Vaccines; Virulence; Virus Replication; Gene Deletion; Genes, Viral
PubMed: 37768081
DOI: 10.1128/jvi.00704-23 -
Viruses Jun 2022From 2017 to 2019, several vaccine-like recombinant strains of lumpy skin disease virus (LSDV) were discovered in Kazakhstan and neighbouring regions of Russia and...
From 2017 to 2019, several vaccine-like recombinant strains of lumpy skin disease virus (LSDV) were discovered in Kazakhstan and neighbouring regions of Russia and China. Shortly before their emergence, the authorities in Kazakhstan launched a mass vaccination campaign with the Neethling-based Lumpivax vaccine. Since none of the other countries in the affected region had used a homologous LSDV vaccine, it was soon suspected that the Lumpivax vaccine was the cause of these unusual LSDV strains. In this study, we performed a genome-wide molecular analysis to investigate the composition of two Lumpivax vaccine batches and to establish a possible link between the vaccine and the recent outbreaks. Although labelled as a pure Neethling-based LSDV vaccine, the Lumpivax vaccine appears to be a complex mixture of multiple CaPVs. Using an iterative enrichment/assembly strategy, we obtained the complete genomes of a Neethling-like LSDV vaccine strain, a KSGP-like LSDV vaccine strain and a Sudan-like GTPV strain. The same analysis also revealed the presence of several recombinant LSDV strains that were (almost) identical to the recently described vaccine-like LSDV strains. Based on their InDel/SNP signatures, the vaccine-like recombinant strains can be divided into four groups. Each group has a distinct breakpoint pattern resulting from multiple recombination events, with the number of genetic exchanges ranging from 126 to 146. The enormous divergence of the recombinant strains suggests that they arose during seed production. The recent emergence of vaccine-like LSDV strains in large parts of Asia is, therefore, most likely the result of a spillover from animals vaccinated with the Lumpivax vaccine.
Topics: Animals; Asia; Cattle; Lumpy Skin Disease; Lumpy skin disease virus; Vaccines, Attenuated; Viral Vaccines
PubMed: 35891412
DOI: 10.3390/v14071429 -
Applied Microbiology and Biotechnology Jan 2022Inactivated and live attenuated vaccines have improved human life and significantly reduced morbidity and mortality of several human infectious diseases. However, these... (Review)
Review
Inactivated and live attenuated vaccines have improved human life and significantly reduced morbidity and mortality of several human infectious diseases. However, these vaccines have faults, such as reactivity or suboptimal efficacy and expensive and time-consuming development and production. Additionally, despite the enormous efforts to develop vaccines against some infectious diseases, the traditional technologies have not been successful in achieving this. At the same time, the concerns about emerging and re-emerging diseases urge the need to develop technologies that can be rapidly applied to combat the new challenges. Within the last two decades, the research of vaccine technologies has taken several directions to achieve safe, efficient, and economic platforms or technologies for novel vaccines. This review will give a brief overview of the current state of the novel vaccine technologies, new vaccine candidates in clinical trial phases 1-3 (listed by European Medicines Agency (EMA) and Food and Drug Administration (FDA)), and vaccines based on the novel technologies which have already been commercially available (approved by EMA and FDA) with the special reference to pandemic COVID-19 vaccines. KEY POINTS: • Vaccines of the new generation follow the minimalist strategy. • Some infectious diseases remain a challenge for the vaccine development. • The number of new vaccine candidates in the late phase clinical trials remains low.
Topics: COVID-19; COVID-19 Vaccines; Communicable Diseases; Humans; SARS-CoV-2; Vaccine Development; Vaccines, Attenuated
PubMed: 34889981
DOI: 10.1007/s00253-021-11713-0 -
Med (New York, N.Y.) Dec 2021In Kenya, the first trial of the attenuated whole organism PfSPZ Vaccine in infants has shown little efficacy against malaria infection, whereas trials in African adults...
In Kenya, the first trial of the attenuated whole organism PfSPZ Vaccine in infants has shown little efficacy against malaria infection, whereas trials in African adults have repeatedly observed protection. Differences in immune responses offer clues to the possible reasons.
Topics: Adult; Clinical Trials as Topic; Humans; Infant; Malaria; Malaria Vaccines; Vaccine Efficacy; Vaccines, Attenuated
PubMed: 35590146
DOI: 10.1016/j.medj.2021.11.002