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Vet Microbiol 2021 Mar 23;256:109048. Epub 2021 Mar 23.

PRRS Research Laboratory, Viral Diseases Division, Animal and Plant Quarantine Agency, Gimcheon, 39660, Republic of Korea. Electronic address:

The objective of this study was to assess protective efficacy of vaccination using CPD-attenuated chimeric PRRSV and Toll like receptor (TLR) agonists (HSP70 c-terminal domain and HSPX) as adjuvants through different inoculation routes. In this study, a chimeric PRRSV composed of two field isolates was synthesized and attenuated by CPD in NSP1 as described in the previous study. The infection of the CPD-attenuated chimeric PRRSV to pigs of 3 weeks-old showed no clinical signs without pathological lesions in necropsy, while it induced improved cross immunity between its parent strains. Read More

Vaccine 2021 Apr 9. Epub 2021 Apr 9.

Bandim Health Project, Department of Clinical Research, University of Southern Denmark, Copenhagen, Denmark; Danish Institute for Advanced Study, University of Southern Denmark, Odense, Denmark.

Introduction: Human non-live vaccines have been associated with detrimental non-specific effects (NSE), particularly in females. A large trial found 2-fold increased overall mortality in girls receiving a new malaria vaccine compared to the rabies vaccine used as a coontrol; a beneficial NSE of the rabies vaccine was proposed. Conversely, in dogs increased mortality was seen in females but not males following rabies vaccination of puppies born to immunized mothers. Read More

AIDS 2021 Apr 6. Epub 2021 Apr 6.

Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa International Centre for Genetic Engineering and Biotechnology, Cape Town, Cape Town, South Africa Department of Biological Sciences, School of Science, University of Eldoret, Kenya Division of Medical Virology, Department of Pathology, and Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa ANOVA Health Institute, Cape Town, Cape Town, South Africa Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa Division of Medical Virology, Department of Pathology, University of Stellenbosch, Cape Town, South Africa.

Objective: Previous studies indicate that transmitted/founder HIV-1 isolates are sensitive to neutralization by the transmitting donor's antibodies. This is true in at least a subset of sexual transmissions. We investigated whether this selection for neutralization-sensitive variants begins in the genital tract of the donor, prior to transmission. Read More

Mol Ther 2021 Apr 5. Epub 2021 Apr 5.

Department of Infectious Diseases/Virology, Medical Faculty, University of Heidelberg, Heidelberg, Germany; BioQuant, University of Heidelberg, Germany; German Center for Infection Research (DZIF) and German Center for Cardiovascular Research (DZHK), partner site Heidelberg, Germany. Electronic address:

Parvoviruses and especially the Adeno-associated virus (AAV) species provide an exciting and versatile platform for the rational design or molecular evolution of human gene therapy vectors, documented by literature from over half a century, hundreds of clinical trials and the recent commercialization of multiple AAV gene therapeutics. For the last three decades, the power of these vectors has been further potentiated through various types of hybrid vectors created by intra- or inter-genus juxtaposition of viral DNA and protein cis elements, or by synergistic complementation of parvoviral features with those of heterologous, prokaryotic or eukaryotic viruses. Here, we provide an overview of the history and promise of this rapidly expanding field of hybrid parvoviral gene therapy vectors, starting with early generations of chimeric particles composed of a recombinant AAV genome encapsidated in shells of synthetic AAVs, or of adeno-, herpes-, baculo- or protoparvoviruses. Read More

J Exp Med 2021 May;218(5)

Department of Medicine, Washington University School of Medicine, St. Louis, MO.

Although Powassan virus (POWV) is an emerging tick-transmitted flavivirus that causes severe or fatal neuroinvasive disease in humans, medical countermeasures have not yet been developed. Here, we developed a panel of neutralizing anti-POWV mAbs recognizing six distinct antigenic sites. The most potent of these mAbs bind sites within domain II or III of the envelope (E) protein and inhibit postattachment viral entry steps. Read More

Front Microbiol 2021 22;12:645530. Epub 2021 Mar 22.

Centre for Research in Agricultural Genomics (CRAG), CSIC-IRTA-UAB-UB, Campus UAB Bellaterra, Barcelona, Spain.

Mixed viral infections in plants involving a potyvirus and other unrelated virus often result in synergistic effects, with significant increases in accumulation of the non-potyvirus partner, as in the case of melon plants infected by the potyvirus (WMV) and the crinivirus (CYSDV). To further explore the synergistic interaction between these two viruses, the activity of RNA silencing suppressors (RSSs) was addressed in transiently co-expressed combinations of heterologous viral products in leaves. While the strong RSS activity of WMV Helper Component Proteinase (HCPro) was unaltered, including no evident additive effects observed when co-expressed with the weaker CYSDV P25, an unexpected negative effect of WMV P1 was found on the RSS activity of P25. Read More

J Virol 2021 Apr 7. Epub 2021 Apr 7.

Key Laboratory of Pathogenic Microbiology and Immunology, Center for Biosafety Mega-Science, Chinese Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China

Currently, immunization with inactivated influenza virus vaccines is the most prevalent method to prevent infections. However, licensed influenza vaccines provide only strain-specific protection and need to be updated and administered yearly; thus, new vaccines that provide broad protection against multiple influenza subtypes are required. In this study, we demonstrated that intradermal immunization with gp96-adjuvanted seasonal influenza monovalent H1N1 split vaccine could induce cross-protection against both group 1 and group 2 influenza A viruses in BALB/c mice models. Read More

Proc Natl Acad Sci U S A 2021 Apr;118(14)

Integrative Biology, University of California, Berkeley, CA 94720;

Dengue is the most prevalent arboviral disease worldwide, and the four dengue virus (DENV) serotypes circulate endemically in many tropical and subtropical regions. Numerous studies have shown that the majority of DENV infections are inapparent, and that the ratio of inapparent to symptomatic infections (I/S) fluctuates substantially year-to-year. For example, in the ongoing Pediatric Dengue Cohort Study (PDCS) in Nicaragua, which was established in 2004, the I/S ratio has varied from 16. Read More

Microorganisms 2021 Mar 26;9(4). Epub 2021 Mar 26.

Smorodintsev Research Institute of Influenza, 197022 St. Petersburg, Russia.

Influenza viruses with an impaired NS1 protein are unable to antagonize the innate immune system and, therefore, are highly immunogenic because of the self-adjuvating effect. Hence, NS1-mutated viruses are considered promising candidates for the development of live-attenuated influenza vaccines and viral vectors for intranasal administration. We investigated whether the immunogenic advantage of the virus expressing only the N-terminal half of the NS1 protein (124 a. Read More

Microorganisms 2021 Mar 26;9(4). Epub 2021 Mar 26.

Department of Research, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), Via E. Tricomi 5, 90127 Palermo, Italy.

Cytomegalovirus (CMV) infection is the most significant viral infection in hosts with compromised immune systems as solid organ transplant patients. Despite significant progress being made in the prevention of CMV disease in these patients, further therapeutic strategies for CMV disease and for the CMV reactivation prevention are needed. Here, we describe the outcome of the infusion of in vitro expanded CMV-reactive T-cells, taken from a healthy CMV-seropositive donor, in a liver-transplanted recipient with a refractory recurrent CMV. Read More

Microorganisms 2021 Mar 26;9(4). Epub 2021 Mar 26.

Laboratory of Animal Products Chemistry, Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan.

The most important characteristics regarding the mucosal infection and immune responses against the Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) as well as the current vaccines against coronavirus disease 2019 (COVID-19) in development or use are revised to emphasize the opportunity for lactic acid bacteria (LAB)-based vaccines to offer a valid alternative in the fight against this disease. In addition, this article revises the knowledge on: (a) the cellular and molecular mechanisms involved in the improvement of mucosal antiviral defenses by beneficial strains, (b) the systems for the expression of heterologous proteins in and (c) the successful expressions of viral antigens in that were capable of inducing protective immune responses in the gut and the respiratory tract after their oral administration. The ability of to express viral antigens, including the spike protein of SARS-CoV-2 and its capacity to differentially modulate the innate and adaptive immune responses in both the intestinal and respiratory mucosa after its oral administration, indicates the potential of this LAB to be used in the development of a mucosal COVID-19 vaccine. Read More

Vaccines (Basel) 2021 Mar 12;9(3). Epub 2021 Mar 12.

Departament d'Enginyeria Química, Biològica i Ambiental, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.

Foot and mouth disease is a livestock acute disease, causing economic losses in affected areas. Currently, control of this disease is performed by mandatory vaccination campaigns using inactivated viral vaccines. In this work, we describe the development of a chimeric VLP-based vaccine candidate for foot-and-mouth disease virus (FMDV), based on the co-expression of the HIV-1 Gag protein and a novel fusion rabies glycoprotein (RVG), which carries in its N-term the FMDV main antigen: the G-H loop. Read More

Viruses 2021 Mar 29;13(4). Epub 2021 Mar 29.

Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan.

Plant viruses can be genetically modified to generate chimeric virus particles (CVPs) carrying heterologous peptides fused on the surface of coat protein (CP) subunits as vaccine candidates. However, some factors may be especially significant in determining the properties of chimeras. In this study, peptides from various sources and of various lengths were inserted into the Bamboo mosaic virusbased (BaMV) vector CP N-terminus to examine the chimeras infecting and accumulating in plants. Read More

Vaccines (Basel) 2021 Mar 8;9(3). Epub 2021 Mar 8.

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.

The roles of the Fc receptor (FcR) in protection or inflammatory disease after respiratory syncytial virus (RSV) vaccination and infection remain unknown. Virus-like particles containing RSV fusion proteins (RSV F-VLPs) induce T-helper type 1 antibody responses and protection against RSV. Heterologous RSV F-VLP prime and formalin-inactivated RSV (FI-RSV) boost vaccination has been reported to be effective in providing protection without inflammatory disease. Read More

Vaccines (Basel) 2021 Mar 14;9(3). Epub 2021 Mar 14.

Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milan, Italy.

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Read More

Front Immunol 2021 9;12:627688. Epub 2021 Mar 9.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.

Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ TNFα double positive CD8 T-cells. Read More

Front Vet Sci 2021 10;8:645561. Epub 2021 Mar 10.

Centro de Investigación en Sanidad Animal (CISA-INIA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain.

Bluetongue virus (BTV) is the causative agent of a disease that affects domestic and wild ruminants and leads to critical economic losses. BTV is an arbovirus from the Reoviridae family that is typically transmitted by the bite of infected midges. BTV possesses multiple serotypes (up to 28 have been described), and immunity to one serotype offers little cross-protection to other serotypes. Read More

Front Immunol 2021 9;12:637613. Epub 2021 Mar 9.

Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.

The humoral immune response plays a crucial role in the combat and protection against many pathogens including the economically most important, highly prevalent, and diverse pig pathogen PRRSV - the Porcine Reproductive and Respiratory Syndrome Virus. In addition to viremia and viral shedding analyses, this study followed the local and systemic humoral immune response of pigs for 63 days upon inoculation with one of three types of Type-2 PRRSV (PRRSV-2) strains - one modified live virus (MLV) vaccine strain, and two lineage 1 PRRSV-2 strains, NC134 and NC174. The local response was analyzed by quantifying immunoglobulin (Ig)A in nasal swabs. Read More

Plant Physiol 2021 Mar 25. Epub 2021 Mar 25.

Shandong Provincial Key Laboratory of Agricultural Microbiology, Department of Plant Pathology, College of Plant Protection, Shandong Agricultural University, Tai'an, Shandong 271018, China.

Cucurbits are economically important crops worldwide. The genomic data of many cucurbits are now available. However, functional analyses of cucurbit genes and non-coding RNAs have been impeded because genetic transformation is difficult for many cucurbitaceous plants. Read More

Plant Biotechnol J 2021 Mar 24. Epub 2021 Mar 24.

Boyce Thompson Institute for Plant Research, Ithaca, NY, USA.

Spodoptera frugiperda (fall armyworm) is a notorious pest that threatens maize production worldwide. Current control measures involve the use of chemical insecticides and transgenic maize expressing Bacillus thuringiensis (Bt) toxins. Although additional transgenes have confirmed insecticidal activity, limited research has been conducted in maize, at least partially due to the technical difficulty of maize transformation. Read More

Cell Rep Med 2021 Mar 3;2(3):100209. Epub 2021 Mar 3.

University of Basel, Department of Biomedicine, Basel, Switzerland.

Therapeutic vaccination regimens inducing clinically effective tumor-specific CD8 T lymphocyte (CTL) responses are an unmet medical need. We engineer two distantly related arenaviruses, Pichinde virus and lymphocytic choriomeningitis virus, for therapeutic cancer vaccination. In mice, life-replicating vector formats of these two viruses delivering a self-antigen in a heterologous prime-boost regimen induce tumor-specific CTL responses up to 50% of the circulating CD8 T cell pool. Read More

Nature 2021 Mar 24. Epub 2021 Mar 24.

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Read More

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Medical Center-University of Freiburg, Department of Internal Medicine II/Molecular Biology, University of Freiburg, 79106 Freiburg, Germany.

Hepadnaviruses, with the human hepatitis B virus as prototype, are small, enveloped hepatotropic DNA viruses which replicate by reverse transcription of an RNA intermediate. Replication is initiated by a unique protein-priming mechanism whereby a hydroxy amino acid side chain of the terminal protein (TP) domain of the viral polymerase (P) is extended into a short DNA oligonucleotide, which subsequently serves as primer for first-strand synthesis. A key component in the priming of reverse transcription is the viral RNA element epsilon, which contains the replication origin and serves as a template for DNA primer synthesis. Read More

Trials 2021 Mar 9;22(1):199. Epub 2021 Mar 9.

CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France.

Background: Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Read More

Front Immunol 2021 4;12:584299. Epub 2021 Mar 4.

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Wooster, OH, United States.

Parenteral administration of killed/inactivated swine influenza A virus (SwIAV) vaccine in weaned piglets provides variable levels of immunity due to the presence of preexisting virus specific maternal derived antibodies (MDA). To overcome the effect of MDA on SwIAV vaccine in piglets, we developed an intranasal deliverable killed SwIAV antigen (KAg) encapsulated chitosan nanoparticles called chitosan-based NPs encapsulating KAg (CS NPs-KAg) vaccine. Further, to target the candidate vaccine to dendritic cells and macrophages which express mannose receptor, we conjugated mannose to chitosan (mCS) and formulated KAg encapsulated mCS nanoparticles called mannosylated chitosan-based NPs encapsulating KAg (mCS NPs-KAg) vaccine. Read More

Biologicals 2021 Mar 17. Epub 2021 Mar 17.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India. Electronic address:

Duck viral enteritis is an acute, contagious infection of Anatidae family members. The disease is caused by Anatid herpesvirus 1 (AnHV-1). The infection of AnHV-1 is controlled by vaccination to the flock with chick embryo adapted attenuated vaccine in developed countries. Read More

NPJ Vaccines 2021 Mar 19;6(1):40. Epub 2021 Mar 19.

GSK, Laval, QC, Canada.

Human infections with avian H7N9 subtype influenza viruses are a major public health concern and vaccines against H7N9 are urgently needed for pandemic preparedness. In early 2013, novel H7N9 influenza viruses emerged in China that caused about 1600 human cases of infection with a high associated case fatality rate. In this study, two H7N9 split virion vaccines with or without AS03 adjuvant were tested in the naive ferret model. Read More

NPJ Vaccines 2021 Mar 19;6(1):41. Epub 2021 Mar 19.

Biomedical Advanced Research and Development Authority (BARDA), Office of the Assistant Secretary for Preparedness and Response (ASPR), Department of Health and Human Services (HHS), Washington, DC, USA.

An unprecedented number of human infections with avian influenza A(H7N9) in the fifth epidemic wave during the winter of 2016-2017 in China and their antigenic divergence from the viruses that emerged in 2013 prompted development of updated vaccines for pandemic preparedness. We report on the findings of a clinical study in healthy adults designed to evaluate the safety and immunogenicity of three dose levels of recombinant influenza vaccine derived from highly pathogenic A/Guangdong/17SF003/2016 (H7N9) virus adjuvanted with AS03 or MF59 oil-in water emulsions. Most of the six study groups meet the FDA CBER-specified vaccine licensure criterion of 70% seroprotection rate (SPR) for hemagglutination inhibition antibodies to the homologous virus. Read More

PLoS Pathog 2021 Mar 18;17(3):e1009391. Epub 2021 Mar 18.

Center for Vaccines and Immunity, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.

There is an urgent need for a vaccine to prevent chronic infection by hepatitis C virus (HCV) and its many genetic variants. The first human vaccine trial, using recombinant viral vectors that stimulate pan-genotypic T cell responses against HCV non-structural proteins, failed to demonstrate efficacy despite significant preclinical promise. Understanding the factors that govern HCV T cell vaccine success is necessary for design of improved immunization strategies. Read More

Virus Res 2021 May 13;297:198392. Epub 2021 Mar 13.

Department of Aquatic Life Medicine, Pukyong National University, Busan, 48513, South Korea. Electronic address:

Water temperature is an important environmental factor for the outbreaks of fish rhabdovirus diseases. In the present study, to know the role of piscine rhabdoviral glycoproteins in the determination of replication temperature, several chimeric snakehead rhabdoviruses (SHRVs) and viral hemorrhagic septicemia viruses (VHSVs) expressing heterologous glycoproteins (rSHRV-Gvhsv, SHRV expressing VHSV G protein; rSHRV-Gsvcv, SHRV expressing spring viremia of carp virus G protein; rVHSV-Gshrv, VHSV expressing SHRV G protein; rVHSV-Gsvcv, VHSV expressing SVCV G protein) were generated using reverse genetics, and their replication characteristics at different temperatures were investigated. Furthermore, based on SHRV minigenome containing a reporter gene, the role of VHSV N, P, and L proteins in the determination of VHSV's low-temperature replication was investigated. Read More