Human Anti-neuraminidase Antibodies Reduce Airborne Transmission of Clinical Influenza Virus Isolates in the Guinea Pig Model

Tan, Jessica; O’Dell, George; Hernandez, Matthew M.; Sordillo, Emilia Mia; Kahn, Zenab; Kriti, Divya; Bakel, Harm van; Ellebedy, Ali H.; Wilson, Patrick C.; Simon, Viviana; Krammer, Florian; McMahon, Meagan

doi:10.1128/jvi.01421-21

Cited by 14 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, neutralising antibody responses to both hemagglutinin and neuraminidase are desirable as they act independently (38) to limit or abolish virus shedding and onward transmission (39) For subcloning into pHR-SIN (38) or the S-FLU expression cassette, 2μg of GeneArt plasmid was digested using EcoRI and NotI in NEBuffer 3.1. Digestion products were run on gels containing 0.7% Agarose and 0.5μg/ml Ethidium Bromide in TAE buffer.…”

Section: Discussionmentioning

confidence: 99%

“…Unlike for many single cycle viruses which lack all or a large part of a viral gene, the full complement of viral antigens should be expressed in RNA, protein and peptide form in the appropriate cellular location after immunisation with CLEARFLU, maximising immunogenicity. In particular, neutralising antibody responses to both hemagglutinin and neuraminidase are desirable as they act independently (38) to limit or abolish virus shedding and onward transmission (39), reduce the risk of pathology in individuals with weak T-cell responses and restrict the opportunity for wildtype virus evolution. CLEARFLU therefore represents a clear advantage over S-FLU and other intranasal vaccine candidates which do not induce neutralising antibody.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A locally administered single cycle influenza vaccine expressing a non-fusogenic stabilised haemagglutinin stimulates strong T-cell and neutralising antibody immunity

Sadler,

Rijal,

Tan

et al. 2024

Preprint

View full text Add to dashboard Cite

Current influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU that is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralising antibodies to hemagglutinin after intranasal administration.This study describes the development of CLEARFLU, a derivative of S-FLU that is designed to add a neutralising antibody response to hemagglutinin. In contrast to S-FLU, which does not express a hemagglutinin molecule at the infected cell surface, CLEARFLU viruses express a stabilised non-fusogenic hemagglutinin. They are equally limited to a single cycle of infection, but induce a neutralising antibody response to the expressed hemagglutinin in addition to the cytotoxic T lymphocyte (CTL) responses to internal proteins and antibodies to neuraminidase induced by S-FLU. This represents a notable advantage as CLEARFLU viruses may provide sterile immunity against strain-matched challenge as well as non-sterile protection against a broad range of influenza viruses.ImportanceInfluenza is a serious public health concern, causing seasonal epidemics as well as pandemics in people. Influenza can also cause severe agricultural losses due to its circulation in farmed poultry and swine. A major challenge in the control of influenza is the diversity of circulating viruses. Developing vaccines which stimulate immunity to a wide array of influenza viruses is therefore important for protecting human and animal populations from disease and death. In this study, we describe an approach for developing influenza vaccines which trigger immune mechanisms shown to induce broad protection against a diversity of viruses, while also conserving the strong protection against specific strains observed in existing vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A locally administered single cycle influenza vaccine expressing a non-fusogenic stabilised haemagglutinin stimulates strong T-cell and neutralising antibody immunity

Sadler,

Rijal,

Tan

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Anti-NA antibodies, although less studied than HA antibodies, have been shown to correlate with protection and reduced viral shedding in humans (43, 44). NA antibodies have also been demonstrated to confer protection and prevent FLUAV transmission in animal models (45). Recent research suggests that N1 antibodies from H1N1-infected individuals can provide heterologous protection against H5N1 (46).…”

Section: Discussionmentioning

confidence: 99%

FLUAV RAM-IGIP: A modified live influenza virus vaccine that enhances humoral and mucosal responses against influenza

Joaquín Cáceres,

Claire Gay,

Jain

et al. 2024

Preprint

View full text Add to dashboard Cite

Current influenza A vaccines fall short, leaving both humans and animals vulnerable. To address this issue, we have developed attenuated modified live virus (MLV) vaccines against influenza using genome rearrangement techniques targeting the internal gene segments of FLUAV. The rearranged M2 (RAM) strategy involves cloning the M2 ORF downstream of the PB1 ORF in segment 2 and incorporating multiple early stop codons within the M2 ORF in segment 7. Additionally, the IgA-inducing protein (IGIP) coding region was inserted into the HA segment to further attenuate the virus and enhance protective mucosal responses. RAM-IGIP viruses exhibit similar growth rates to wild type (WT) viruses in vitro and remain stable during multiple passages in cells and embryonated eggs. The safety, immunogenicity, and protective efficacy of the RAM-IGIP MLV vaccine against the prototypical 2009 pandemic H1N1 strain A/California/04/2009 (H1N1) (Ca/04) were evaluated in Balb/c mice and compared to a prototypic cold-adapted live attenuated virus vaccine. The results demonstrate that the RAM-IGIP virus exhibits attenuated virulence in vivo. Mice vaccinated with RAM-IGIP and subsequently challenged with an aggressive lethal dose of the Ca/04 strain exhibited complete protection. Analysis of the humoral immune response revealed that the inclusion of IGIP enhanced the production of neutralizing antibodies and augmented the antibody-dependent cellular cytotoxicity response. Similarly, the RAM-IGIP potentiated the mucosal immune response against various FLUAV subtypes. Moreover, increased antibodies against NP and NA responses were observed. These findings support the development of MLVs utilizing genome rearrangement strategies in conjunction with the incorporation of immunomodulators.

show abstract

“…Recombinant NA and NA-VLPs have been shown to induce high titers of anti-NA antibodies that protect mice and ferrets from challenge infections [27][28][29] . Furthermore, recombinant NA-based vaccines have been shown to inhibit influenza virus transmission in the guinea pig model 30 . In these studies, heterosubtypic immunity was not detected, although cross-protection against viruses belonging to the same subtype was observed 27 .…”

Section: Discussionmentioning

confidence: 99%

A broadly protective human monoclonal antibody targeting the sialidase activity of influenza A and B virus neuraminidases

et al. 2022

View full text Add to dashboard Cite

Improved vaccines and antiviral agents that provide better, broader protection against seasonal and emerging influenza viruses are needed. The viral surface glycoprotein hemagglutinin (HA) is a primary target for the development of universal influenza vaccines and therapeutic antibodies. The other major surface antigen, neuraminidase (NA), has been less well studied as a potential target and fewer broadly reactive anti-NA antibodies have been identified. In this study, we isolate three human monoclonal antibodies that recognize NA from A/H1N1 subtypes, and find that one of them, clone DA03E17, binds to the NA of A/H3N2, A/H5N1, A/H7N9, B/Ancestral-lineage, B/Yamagata-lineage, and B/Victoria-lineage viruses. DA03E17 inhibits the neuraminidase activity by direct binding to the enzyme active site, and provides in vitro and in vivo protection against infection with several types of influenza virus. This clone could, therefore, be useful as a broadly protective therapeutic agent. Moreover, the neutralizing epitope of DA03E17 could be useful in the development of an NA-based universal influenza vaccine.

show abstract

Human Anti-neuraminidase Antibodies Reduce Airborne Transmission of Clinical Influenza Virus Isolates in the Guinea Pig Model

Cited by 14 publications

References 28 publications

A locally administered single cycle influenza vaccine expressing a non-fusogenic stabilised haemagglutinin stimulates strong T-cell and neutralising antibody immunity

A locally administered single cycle influenza vaccine expressing a non-fusogenic stabilised haemagglutinin stimulates strong T-cell and neutralising antibody immunity

FLUAV RAM-IGIP: A modified live influenza virus vaccine that enhances humoral and mucosal responses against influenza

A broadly protective human monoclonal antibody targeting the sialidase activity of influenza A and B virus neuraminidases

Contact Info

Product

Resources

About