Identification of a Live Attenuated Vaccine Candidate for Tularemia Prophylaxis

African swine fever virus (ASFV) is causing a devastating pandemic in domestic and wild swine within an extended geographical area from Central Europe to East Asia resulting in economic losses for the regional swine industry. There are no commercial vaccines, therefore disease control relies on identification and culling of infected animals. We report here that the deletion of the ASFV gene A137R from the highly virulent ASFV-Georgia2010 (ASFV-G) isolate induces a significant attenuation of virus virulence in swine. A recombinant virus lacking the A137R gene, ASFV-G-ΔA137R, was developed to assess the role of this gene in ASFV virulence in domestic swine. Animals inoculated intramuscularly with 10 2 HAD 50 of ASFV-G-ΔA137R remained clinically healthy during the 28 day observational period. All animals inoculated with ASFV-G-ΔA137R had medium to high viremia titers and developed a strong virus-specific antibody response. Importantly, all ASFV-G-ΔA137R-inoculated animals were protected when challenged with the virulent parental strain ASFV-G. No evidence of replication of challenge virus was observed in the ASFV-G-ΔA137R-inoculated animals. Therefore, ASFV-G-ΔA137R is a novel potential live attenuated vaccine candidate and one of the few experimental vaccine strains reported to induce protection against the highly virulent ASFV Georgia virus that is the cause of the current Eurasian pandemic. Importance: No commercial vaccine is available to prevent African swine fever. The ASF pandemic caused by ASFV Georgia2007 (ASFV-G) is seriously affecting pork production in a contiguous area from Central Europe to East Asia. Here we report the rational development of a potential live attenuated vaccine strain by deleting a virus-specific gene, A137R, from the genome of ASFV-G. The resulting virus presented a completely attenuated phenotype and, importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. ASFV-G-ΔA137R confers protection even at low doses (10 2 HAD 50 ) demonstrating its potential as a vaccine candidate. Therefore, ASFV-G-ΔA137R is a novel experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.

Download Full-text

Vibrio harveyi protease deletion mutant as a live attenuated vaccine candidate against vibriosis and transcriptome profiling following vaccination for Epinephelus fuscoguttatus

Aquaculture International ◽

10.1007/s10499-018-0311-x ◽

2018 ◽

Vol 27 (1) ◽

pp. 125-140 ◽

Cited By ~ 6

Author(s):

Aslizah Mohd-Aris ◽

Mohd-Zamri Saad ◽

Hassan Mohd Daud ◽

Mohd Termizi Yusof ◽

Md Yasin Ina-Salwany

Keyword(s):

Deletion Mutant ◽

Vaccine Candidate ◽

Vibrio Harveyi ◽

Transcriptome Profiling ◽

Live Attenuated Vaccine ◽

Attenuated Vaccine ◽

Epinephelus Fuscoguttatus

Download Full-text

A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region

mBio ◽

10.1128/mbio.00186-20 ◽

2020 ◽

Vol 11 (2) ◽

Cited By ~ 3

Author(s):

Yingyun Cai ◽

Masaharu Iwasaki ◽

Daisuke Motooka ◽

David X. Liu ◽

Shuiqing Yu ◽

...

Keyword(s):

Intergenic Region ◽

Guinea Pigs ◽

Cultured Cells ◽

Vaccine Candidate ◽

Lassa Fever ◽

Lassa Virus ◽

Wild Type ◽

Live Attenuated Vaccine ◽

Attenuated Vaccine ◽

Western Africa

ABSTRACT Lassa virus (LASV) poses a significant public health problem within the regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding intergenic region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication. IMPORTANCE Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding intergenic region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.

Download Full-text

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

Journal of Virology ◽

10.1128/jvi.01568-20 ◽

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.

Download Full-text

Evaluation of a virus derived from MDCK cells infected persistently with influenza A virus as a potential live-attenuated vaccine candidate in the mouse model

Journal of Medical Virology ◽

10.1002/jmv.21148 ◽

2008 ◽

Vol 80 (5) ◽

pp. 888-894 ◽

Cited By ~ 3

Author(s):

Beixing Liu ◽

Md. Jaber Hossain ◽

Isamu Mori ◽

Yoshinobu Kimura

Keyword(s):

Mouse Model ◽

Influenza A Virus ◽

Influenza A ◽

Vaccine Candidate ◽

Mdck Cells ◽

Live Attenuated Vaccine ◽

Attenuated Vaccine

Download Full-text

The 16MΔvjbR as an ideal live attenuated vaccine candidate for differentiation between Brucella vaccination and infection

Veterinary Microbiology ◽

10.1016/j.vetmic.2011.03.031 ◽

2011 ◽

Vol 151 (3-4) ◽

pp. 354-362 ◽

Cited By ~ 27

Author(s):

Yufei Wang ◽

Yaoxia Bai ◽

Qing Qu ◽

Jie Xu ◽

Yanfen Chen ◽

...

Keyword(s):

Vaccine Candidate ◽

Live Attenuated Vaccine ◽

Attenuated Vaccine

Download Full-text

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

10.1101/2021.02.15.430863 ◽

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.

Download Full-text