Delving into the Latest Updates on Influenza A virus H7N9 vaccine(Medicago) with Synapse

Overview

Basic Info

Drug Type

Virus-like particle vaccine, Prophylactic vaccine, Genetically engineered subunit vaccine

Synonyms

H7 VLP influenza vaccine( Medicago), H7 Vlp Influenza Vaccine, H7 vaccine

+ [9]

Target

TLR4 x hemagglutinin

Action

agonists, modulators

Mechanism

TLR4 agonists(Toll like receptor 4 agonists), hemagglutinin modulators(Influenza virus hemagglutinin glycoproteins modulators)

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication-

Inactive Indication

Influenza, Human

Originator Organization

Medicago, Inc.

Active Organization-

Inactive Organization

Medicago, Inc.

License Organization-

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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ABSTRACTNeutralizing antibodies (nAbs) are important for the treatment of emerging viral diseases and for effective vaccine development. In this study, we generated and evaluated three nAbs (1H9, 2D7, and C4H4) against H7N9 influenza viruses and found that they differ in their ability to inhibit viral attachment, membrane fusion, and egress. We resolved the cryo-electron microscopy (cryo-EM) structures of H7N9 hemagglutinin (HA) alone and in complex with the nAb antigen-binding fragments (Fabs) and identified the HA head-located epitope for each nAb, thereby revealing the molecular basis and key residues that determine the differences in these nAbs in neutralizing H7N9 viruses. Moreover, we found that the humanized nAb CC4H4 provided complete protection in mice against death caused by a lethal H7N9 virus infection, even when nAb was given 3 days after the mice were infected. These findings provide new insights into the neutralizing mechanism and structural basis for the rational design of H7N9 virus vaccines and therapeutics.IMPORTANCEH7N9 viruses have caused severe infections in both birds and humans since their emergence in early 2013 in China. Their persistent presence and variation in avian populations pose a significant threat to both poultry and humans. There are no treatments for human infections. In this study, we thoroughly investigated the neutralization mechanisms, structural basis, and therapeutic effects of three nAbs (1H9, 2D7, and C4H4) against H7N9 viruses. We revealed the molecular determinants underlying the varied performances of the three nAbs in neutralizing H7N9 viruses and protecting H7N9-infected mice. These insights provide a solid foundation for the rational design of vaccines and therapeutics against H7N9 viruses.

31 Dec 2024·Virulence

Characterization of Conserved Evolution in H7N9 Avian Influenza Virus Prior Mass Vaccination

Article

Author: Hu, Shunlin ; Gu, Min ; Cai, Kairui ; Peng, Daxin ; Wu, Huiguang ; Liu, Xiufan ; Su, Shuo ; Ding, Chan ; Song, Xiaoli ; Hu, Jiao ; Wang, Xiaoquan ; He, Dongchang ; Wang, Xiyue ; Liu, Xiaowen

Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.

01 Dec 2024·Veterinary Immunology and Immunopathology

Efficacy of the H7N9 vaccine as a candidate for the Korean avian influenza antigen bank

Article

Author: Lee, Yoon kyoung ; Lee, Youn-Jeong ; Do, Hyerim ; Lee, Yoon Kyoung ; Cho, Hyun-Kyu ; Kim, Seong-Hee ; Sagong, Mingeun

The avian influenza A virus (H7N9), first detected in China in 2013, is a zoonotic virus that remains persistent in bird populations despite a decline in human cases owing to control measures. Therefore, this study aimed to develop a vaccine as one preventive strategy in anticipation of the potential entry of H7N9 into Korea. Using the hemagglutinin and neuraminidase consensus sequences of H7N9 from 2018-2019, a recombinant H7N9 vaccine, rgAPQAH7N9, was developed, and its protective efficacy in specific pathogen-free chickens was evaluated. The rgAPQAH7N9 vaccine exhibited proliferation in eggs and demonstrated high immunogenicity, with a hemagglutination inhibition titer of 9.3 log₂. Furthermore, the vaccine provided complete protection, as vaccinated chickens did not exhibit clinical signs or viral shedding. Moreover, when the rgAPQAH7N9 vaccine was boosted, the resulting immunity was long-lasting, with hemagglutination inhibition titers > 7 log2 persisting after 6 months. Therefore, the rgAPQAH7N9 vaccine virus may be considered a potential candidate for inclusion in the avian influenza antigen bank to ensure preparedness for emergency vaccination in poultry.

100 Deals associated with Influenza A virus H7N9 vaccine(Medicago)

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