Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses.

Human COBRA 2 vaccine contains two major epitopes that are responsible for eliciting neutralizing antibody responses against heterologous clades of viruses. Vaccine. 2019 Nov 13;: Authors: Nuñez IA, Ross TM Abstract Highly pathogenic H5N1 influenza viruses continue to spread around the globe and reassort with low pathogenic avian influenza viruses often resulting in morbidity and mortality to not only waterfowl, but also poultry. Our group previously developed two hemagglutinin (HA) based vaccines using a methodology termed computationally optimized broadly reactive antigen (COBRA). Each of these HA antigens, Human COBRA 2 (Hu-CO) and Human-Avian COBRA 2 (Hu-Av CO) elicit antibodies with hemagglutination-inhibition (HAI) activity against viruses from various clades, but not always the same viruses. Here, we have sought to identify residues in these two HA molecules that are critical fordifferential HAI activity against various H5Nx influenza viruses. The two HA antigens are remarkedly similar in the globular head region, except for 4 residues at amino acids 140, 141, 155, and 156. By mutating these amino acids in each HA antigen, chimeric HA proteins were used to elicit immune responses in mice. When the Asn-Thr pair at position 155-156 in the Hu-CO HA was converted to the Ser-Ala residues found in the Hu-Av CO HA, the elicited antibodies lost HAI activity against clade 2.3.2.1 H5Nx viruses, such as A/Hubei/01/2010. When this Asn-Thr motif was add...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research

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This study demonstrates the usefulness of the HPAI H5N1 HA2 E29 epitope as a DIVA antigen in HPAI H5N1 vaccinated and infected chickens.Research Highlight E29 (HA2 position 488-516) epitope is antigenic in chickenAntibodies to E29 are elicited following live H5N1 virus infection in chickenE29 epitope is a potential DIVA antigen for use in ELISA. PMID: 31738584 [PubMed - as supplied by publisher]
Source: Avian Pathology - Category: Pathology Authors: Tags: Avian Pathol Source Type: research
CONCLUSION: We report on an assay to measure stem-specific ADCC activity using SS np probes. Our results indicate high prevalence of HA-stem antibodies with cross-reactive ADCC activity. Such assay could be utilized in the assessment of next generation influenza vaccines. PMID: 31735504 [PubMed - as supplied by publisher]
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
Abstract BACKGROUND: The emergence and spread of highly pathogenic avian influenza (H5N1) viruses have raised global concerns of a possible human pandemic, spurring efforts towards H5N1 influenza vaccine development and improvements in vaccine administration methods. We previously showed that a prime-boost vaccination strategy induces robust and broadly cross-reactive antibody responses against the hemagglutinin globular head domain. Here, we specifically measure antibodies against the conserved hemagglutinin stem region in serum samples obtained from the prior study to determine whether stalk-reactive antibodies ...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
In this study, we investigated the delivery of insect cell culture-derived recombinant hemagglutinin protein (HA) of A/H5N1/Vietnam/1203/2004 virus using CaPNP. We evaluated the vaccine immunogenicity in mice following two intramuscular doses of 3 μg antigen combined with escalating doses of CaPNP. Our data showed CaPNP-adjuvanted HA(H5N1) vaccines eliciting significantly higher IgG, hemagglutination inhibition, and virus neutralization titers compared to non-adjuvanted vaccine. Among the four adjuvant doses that were tested, CaPNP at 0.24% final concentration elicited the highest IgG and neutralizing antibody tite...
Source: AAPS PharmSciTech - Category: Drugs & Pharmacology Authors: Tags: AAPS PharmSciTech Source Type: research
Contributors : Hang Xie ; Courtney L FinchSeries Type : Expression profiling by RT-PCROrganism : Mus musculusAge-matched BALB/c female mice were implanted subcutaneously with slow release estradiol (E2) pellets (35 mg/pellet/mouse) or similar-sized placebo pellets .One week post-implantation, mice were infected intranasally with a sublethal dose of H5N1 A/Vietnam/1203/2004 vaccine reassortant bearing a monobasic HA cleavage site. Mouse lungs were harvested on day 1 post infection and total RNA was extracted using QIAgen RNeasy microarray tissue mini kit. A total of 100 µg high-quality RNA was reverse transcribed usin...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by RT-PCR Mus musculus Source Type: research
In this study, we evaluated the efficacy of soluble recombinant hemagglutinin (HA) protein produced in human cell culture (Expi293F cells) as an influenza vaccine against homosubtypic and heterosubtypic influenza virus challenges in mice. Mice were immunized intramuscularly with purified soluble HA protein of H1N1pdm09 virus and then challenged with a lethal dose of H1N1pdm09, seasonal H3N2, or highly pathogenic avian influenza (HPAI) H5N1 virus. Vaccinated mice showed better morbidity than mock-vaccinated mice following H1N1pdm09 challenge. By contrast, all mice died following H3N2 challenge. Interestingly, all vaccinated...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
The highly pathogenic (HP) avian influenza virus (AIV), H5N1 and reassortant H5-subtype HPAIVs, H5N2, H5N6, and H5N8, cause high mortality in domestic birds, resulting in economic losses in the poultry industry. H5N1 and H5N6 also pose significant public health risks and H5N1 viruses are a permanent pandemic threat. To control HPAIVs, eukaryotic expression systems have traditionally been exploited to produce vaccines based on hemagglutinin (HA), a protective viral antigen. In contrast, we used a bacterial expression system to produce vaccine targeting the HA protein. A fragment of the HA ectodomain from H5N1, with a multib...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsThis study demonstrates a rapid decline of AS03 from the quadriceps muscles of mice as compared to conventional SQ/W emulsion adjuvant, with an increased transfer to mechanistically relevant tissues such as local lymph nodes. Systemic tissue exposure to potential toxicological target tissues was very low.
Source: Regulatory Toxicology and Pharmacology - Category: Toxicology Source Type: research
CONCLUSIONS: This study demonstrates a rapid decline of AS03 from the quadriceps muscles of mice as compared to conventional SQ/W emulsion adjuvant, with an increased transfer to mechanistically relevant tissues such as local lymph nodes. Systemic tissue exposure to potential toxicological target tissues was very low. PMID: 31381939 [PubMed - as supplied by publisher]
Source: Regulatory Toxicology and Pharmacology : RTP - Category: Toxicology Authors: Tags: Regul Toxicol Pharmacol Source Type: research
Publication date: Available online 11 July 2019Source: Veterinary MicrobiologyAuthor(s): Jiayun Yang, Zhengxiang Wang, Yingying Du, Yane Jia, Liang Wang, Shuai Xu, Qiyun ZhuAbstractDuring 2012―2015, six H5N1 avian influenza viruses were isolated from domestic birds and the environment around Qinghai Lake. Phylogenetic analysis of HA genes revealed that A/chicken/Gansu/XG2/2012 (CK/GS/XG2/12) belonged to clade 2.3.2.1a, while A/environment/Qinghai/1/2013 (EN/QH/1/13), A/chicken/Qinghai/QH1/2015 (CK/QH/QH1/15), A/chicken/Qinghai/QH2/2015 (CK/QH/QH2/15), A/chicken/Qinghai/QH3/2015 (CK/QH/QH3/15), and A/goose/Qinghai/QH6/201...
Source: Veterinary Microbiology - Category: Veterinary Research Source Type: research
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