scholarly journals A single-dose live attenuated chimeric vaccine candidate against Zika virus

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Wei-Xin Chin ◽  
Regina Ching Hua Lee ◽  
Parveen Kaur ◽  
Tian Sheng Lew ◽  
Thinesshwary Yogarajah ◽  
...  
Keyword(s):  
Virus Vaccine ◽  
Zika Virus ◽  
Vaccine Candidate ◽  
Effective Vaccine ◽  
Neutralising Antibodies ◽  
Live Attenuated Vaccine ◽  
Live Virus ◽  
Plaque Phenotype ◽  
Chimeric Vaccine

AbstractThe mosquito-borne Zika virus is an emerging pathogen from the Flavivirus genus for which there are no approved antivirals or vaccines. Using the clinically validated PDK-53 dengue virus vaccine strain as a backbone, we created a chimeric dengue/Zika virus, VacDZ, as a live attenuated vaccine candidate against Zika virus. VacDZ demonstrates key markers of attenuation: small plaque phenotype, temperature sensitivity, attenuation of neurovirulence in suckling mice, and attenuation of pathogenicity in interferon deficient adult AG129 mice. VacDZ may be administered as a traditional live virus vaccine, or as a DNA-launched vaccine that produces live VacDZ in vivo after delivery. Both vaccine formulations induce a protective immune response against Zika virus in AG129 mice, which includes neutralising antibodies and a strong Th1 response. This study demonstrates that VacDZ is a safe and effective vaccine candidate against Zika virus.

scholarly journals Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach

2008 ◽  
Vol 82 (21) ◽  
pp. 10580-10590 ◽  
Author(s):  
Rong Hai ◽  
Luis Martínez-Sobrido ◽  
Kathryn A. Fraser ◽  
Juan Ayllon ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type I ◽  
Live Attenuated Vaccine ◽  
Live Virus ◽  
B Virus

ABSTRACT Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against infections with these viruses. Here, we report the construction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates. Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. The resulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and in vivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR−/− mice was confirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.

scholarly journals Novel Mutant Phospholipase D from Hemiscorpius lepturus Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1673 ◽  
Author(s):  
Abouzar Soleimani Moez ◽  
Reza H. Sajedi ◽  
Kamran Pooshang Bagheri ◽  
Jean-Marc Sabatier ◽  
Delavar Shahbazzadeh
Keyword(s):  
Phospholipase D ◽  
Vaccine Candidate ◽  
Clinical Symptoms ◽  
Scorpion Venom ◽  
Effective Vaccine ◽  
Cytotoxic Effects ◽  
In Vivo Tests ◽  
Neurotoxic Effects ◽  
Hemiscorpius Lepturus

Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues—His12 and His48—into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD100 of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.

scholarly journals Complete Genome Sequences of Four African Horse Sickness Virus Strains from a Commercial Tetravalent Live Attenuated Vaccine

2015 ◽  
Vol 3 (6) ◽  
Author(s):  
Alan J. Guthrie ◽  
Peter Coetzee ◽  
Darren P. Martin ◽  
Carina W. Lourens ◽  
Estelle H. Venter ◽  
...  
Keyword(s):  
South African ◽  
Virus Vaccine ◽  
Complete Genome ◽  
African Horse Sickness ◽  
African Horse Sickness Virus ◽  
Genome Sequences ◽  
Live Attenuated Vaccine ◽  
Live Virus ◽  
Live Virus Vaccine ◽  
Virus Strains

This is a report of the complete genome sequences of plaque-selected isolates of each of the four virus strains included in a South African commercial tetravalent African horse sickness attenuated live virus vaccine.

scholarly journals Recombinant Sendai Virus Expressing the G Glycoprotein of Respiratory Syncytial Virus (RSV) Elicits Immune Protection against RSV

2004 ◽  
Vol 78 (11) ◽  
pp. 6043-6047 ◽  
Author(s):  
Toru Takimoto ◽  
Julia L. Hurwitz ◽  
Chris Coleclough ◽  
Cecilia Prouser ◽  
Sateesh Krishnamurthy ◽  
...  
Keyword(s):  
Virus Type ◽  
Virus Vaccine ◽  
Reverse Genetics ◽  
Sendai Virus ◽  
Parainfluenza Virus ◽  
Effective Vaccine ◽  
Live Virus ◽  
Live Virus Vaccine ◽  
Syncytial Virus

ABSTRACT Although RSV causes serious pediatric respiratory disease, an effective vaccine does not exist. To capture the strengths of a live virus vaccine, we have used the murine parainfluenza virus type 1 (Sendai virus [SV]) as a xenogeneic vector to deliver the G glycoprotein of RSV. It was previously shown (J. L. Hurwitz, K. F. Soike, M. Y. Sangster, A. Portner, R. E. Sealy, D. H. Dawson, and C. Coleclough, Vaccine 15:533-540, 1997) that intranasal SV protected African green monkeys from challenge with the related human parainfluenza virus type 1 (hPIV1), and SV has advanced to clinical trials as a vaccine for hPIV1 (K. S. Slobod, J. L. Shenep, J. Lujan-Zilbermann, K. Allison, B. Brown, R. A. Scroggs, A. Portner, C. Coleclough, and J. L. Hurwitz, Vaccine, in press). Recombinant SV expressing RSV G glycoprotein was prepared by using reverse genetics, and intranasal inoculation of cotton rats elicited RSV-specific antibody and elicited protection from RSV challenge. RSV G-recombinant SV is thus a promising live virus vaccine candidate for RSV.

scholarly journals Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as a live virus vaccine candidate

EBioMedicine ◽  
2020 ◽  
Vol 62 ◽  
pp. 103132
Author(s):  
Weina Sun ◽  
Sarah R. Leist ◽  
Stephen McCroskery ◽  
Yonghong Liu ◽  
Stefan Slamanig ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Virus Vaccine ◽  
Newcastle Disease ◽  
Vaccine Candidate ◽  
Spike Protein ◽  
Live Virus ◽  
Live Virus Vaccine

scholarly journals Preclinical Efficacy of a Lipooligosaccharide Peptide Mimic Candidate Gonococcal Vaccine

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Sunita Gulati ◽  
Michael W. Pennington ◽  
Andrzej Czerwinski ◽  
Darrick Carter ◽  
Bo Zheng ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Neisseria Gonorrhoeae ◽  
Vaccine Candidate ◽  
Peptide Vaccine ◽  
Human Infection ◽  
Effective Vaccine ◽  
Infection Model ◽  
Content Type ◽  
Peptide Mimic

ABSTRACT The global spread of multidrug-resistant strains of Neisseria gonorrhoeae constitutes a public health emergency. With limited antibiotic treatment options, there is an urgent need for development of a safe and effective vaccine against gonorrhea. Previously, we constructed a prototype vaccine candidate comprising a peptide mimic (mimitope) of a glycan epitope on gonococcal lipooligosaccharide (LOS), recognized by monoclonal antibody 2C7. The 2C7 epitope is (i) broadly expressed as a gonococcal antigenic target in human infection, (ii) a critical requirement for gonococcal colonization in the experimental setting, and (iii) a virulence determinant that is maintained and expressed by gonococci. Here, we have synthesized to >95% purity through a relatively facile and economical process a tetrapeptide derivative of the mimitope that was cyclized through a nonreducible thioether bond, thereby rendering the compound homogeneous and stable. This vaccine candidate, called TMCP2, when administered at 0, 3, and 6 weeks to BALB/c mice at either 50, 100 or 200 μg/dose in combination with glucopyranosyl lipid A-stable oil-in-water nanoemulsion (GLA-SE; a Toll-like receptor 4 and TH1-promoting adjuvant), elicited bactericidal IgG and reduced colonization levels of gonococci in experimentally infected mice while accelerating clearance by each of two different gonococcal strains. Similarly, a 3-dose biweekly schedule (50 μg TMCP2/dose) was also effective in mice. We have developed a gonococcal vaccine candidate that can be scaled up and produced economically to a high degree of purity. The candidate elicits bactericidal antibodies and is efficacious in a preclinical experimental infection model. IMPORTANCE Neisseria gonorrhoeae has become resistant to most antibiotics. The incidence of gonorrhea is also sharply increasing. A safe and effective antigonococcal vaccine is urgently needed. Lipooligosaccharide (LOS), the most abundant outer membrane molecule, is indispensable for gonococcal pathogenesis. A glycan epitope on LOS that is recognized by monoclonal antibody (MAb) 2C7 (called the 2C7 epitope) is expressed almost universally by gonococci in vivo. Previously, we identified a peptide mimic (mimitope) of the 2C7 epitope, which when configured as an octamer and used as an immunogen, attenuated colonization of mice by gonococci. Here, a homogenous, stable tetrameric derivative of the mimitope, when combined with a TH1-promoting adjuvant and used as an immunogen, also effectively attenuates gonococcal colonization of mice. This candidate peptide vaccine can be produced economically, an important consideration for gonorrhea, which affects socioeconomically underprivileged populations disproportionately, and represents an important advance in the development of a gonorrhea vaccine.

scholarly journals A novel live attenuated RSV vaccine candidate with mutations in the L protein SAM binding site and the G protein cleavage site is protective in cotton rats and a rhesus macaque

2020 ◽  
Author(s):  
Tiffany Jenkins ◽  
Rongzhang Wang ◽  
Olivia Harder ◽  
Miaoge Xue ◽  
Phylip Chen ◽  
...  
Keyword(s):  
Binding Site ◽  
Rhesus Macaque ◽  
Vaccine Candidate ◽  
Vero Cells ◽  
Virus Yield ◽  
Vaccine Production ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Cotton Rats

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in children < 5 years of age worldwide, infecting the majority of infants in their first year of life. Despite the widespread impact of this virus, no vaccine is currently available. For over 50 years, live attenuated vaccines (LAV) have been shown to protect against other childhood viral infections, offering the advantage of presenting all viral proteins to the immune system for stimulation of both B and T cell responses and memory. The RSV LAV candidate described here, rgRSV-L(G1857A)-G(L208A), contains two modifications: an attenuating mutation in the S-adenosylmethionine (SAM) binding site of the viral mRNA cap methyltransferase (MTase) within the large (L) polymerase protein and a mutation in the attachment (G) glycoprotein that inhibits its cleavage during production in Vero cells, resulting in virus with a “non-cleaved G” (ncG). RSV virions containing the ncG have an increased ability to infect primary well-differentiated human bronchial epithelial (HBE) cultures which model the in vivo site of immunization, the ciliated airway epithelium. This RSV LAV candidate is produced efficiently in Vero cells, is highly attenuated in HBE cultures, efficiently induces neutralizing antibodies that are long-lasting, and provides protection against an RSV challenge in the cotton rat, without causing enhanced disease. Similar results were obtained in a rhesus macaque. Importance Globally, RSV is a major cause of death in children under one year of age, yet no vaccine is available. We have generated a novel RSV live attenuated vaccine candidate containing mutations in the L and G proteins. The L polymerase mutation does not inhibit virus yield in Vero cells, the cell type required for vaccine production, but greatly reduces virus spread in HBE cultures, a logical in vitro predictor of in vivo attenuation. The G attachment protein mutation reduces its cleavage in Vero cells, thereby increasing vaccine virus yield, making vaccine production more economical. In cotton rats, this RSV vaccine candidate is highly attenuated at a dose of 105 PFU and completely protective following immunization with 500 PFU, 200-fold less than the dose usually used in such studies. It also induced long-lasting antibodies in cotton rats and protected a rhesus macaque from RSV challenge. This mutant virus is an excellent RSV live attenuated vaccine candidate.

scholarly journals Live attenuated SARS-CoV-2 vaccine candidate: Protective immunity without serious lung lesions in Syrian hamsters

2021 ◽  
Author(s):  
Shinya Okamura ◽  
Akiho Kashiwabara ◽  
Hidehiko Suzuki ◽  
Shiori Ueno ◽  
Paola Miyazato ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Nonstructural Protein ◽  
Wild Type Virus ◽  
Temperature Sensitive ◽  
Live Attenuated Vaccine ◽  
Syrian Hamsters ◽  
Attenuated Vaccine

AbstractVarious COVID-19 vaccine candidates are currently under clinical trial. However, no live attenuated vaccine has been developed yet, despite their generally high efficacy. Here, we established temperature-sensitive mutant strains of SARS-CoV-2, whose growth was significantly slower than that of the parent strain at 37°C. One of the strains, A50-18, which presented mutations in nonstructural protein 14, did not replicate at all at 37°C in vitro. In vivo experiments demonstrated that this strain replicated inefficiently in the lungs of Syrian hamsters, and intra-nasal inoculation induced sufficient anti-SARS-CoV-2-neutralizing antibodies to protect against wild type virus infection. These results suggest that the A50-18 strain could be a promising live attenuated vaccine candidate against SARS-CoV-2.One Sentence SummaryA live attenuated virus provided immunity against SARS-CoV-2 in an animal model, making it a promising vaccine candidate.

scholarly journals Enemy of My Enemy: A Novel Insect-Specific Flavivirus Offers a Promising Platform for a Zika Virus Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1142
Author(s):  
Danielle Porier ◽  
Sarah Wilson ◽  
Dawn Auguste ◽  
Andrew Leber ◽  
Sheryl Coutermarsh-Ott ◽  
...  
Keyword(s):  
Public Health ◽  
Single Dose ◽  
Zika Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Viral Disease ◽  
Trade Offs

Vaccination remains critical for viral disease outbreak prevention and control, but conventional vaccine development typically involves trade-offs between safety and immunogenicity. We used a recently discovered insect-specific flavivirus as a vector in order to develop an exceptionally safe, flavivirus vaccine candidate with single-dose efficacy. To evaluate the safety and efficacy of this platform, we created a chimeric Zika virus (ZIKV) vaccine candidate, designated Aripo/Zika virus (ARPV/ZIKV). ZIKV has caused immense economic and public health impacts throughout the Americas and remains a significant public health threat. ARPV/ZIKV vaccination showed exceptional safety due to ARPV/ZIKV’s inherent vertebrate host-restriction. ARPV/ZIKV showed no evidence of replication or translation in vitro and showed no hematological, histological or pathogenic effects in vivo. A single-dose immunization with ARPV/ZIKV induced rapid and robust neutralizing antibody and cellular responses, which offered complete protection against ZIKV-induced morbidity, mortality and in utero transmission in immune-competent and -compromised murine models. Splenocytes derived from vaccinated mice demonstrated significant CD4+ and CD8+ responses and significant cytokine production post-antigen exposure. Altogether, our results further support that chimeric insect-specific flaviviruses are a promising strategy to restrict flavivirus emergence via vaccine development.

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