An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo

Wilson, Jason R.; Guo, Zhu; Reber, A.; Kamal, Ram P.; Music, Nedzad; Gansebom, Shane; Bai, Yaohui; Levine, Min Z.; Carney, P.J.; Tzeng, Wen-Pin; Stevens, James; York, Ian A.

doi:10.1016/j.antiviral.2016.10.001

Cited by 33 publications

(48 citation statements)

References 47 publications

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“…It is interesting that MAbs which bind to the HB region, e.g., 1E8 and 10F4, did not block virus infection, implying that the HB site is not required for virus entry. Our data and the findings of Wilson et al (21) indicate that MAbs to the HB site can protect mice from lethal A(H7N9) virus challenge, and for this reason the HB site may be an attractive target for antibodies selected for development as antivirals.…”

Section: Discussionsupporting

confidence: 72%

“…Escape mutant selection and site mutagenesis in our study identified residues 368, 370, 371, 373, 400, and 434 as critical contacts for MAbs 1E8, 5H11, 7F12, and 10F4. These amino acids are also within defined epitopes recognized by G70C NA-specific MAbs (17,20,21,40). Amino acid 345 appears to be relatively distant from other identified amino acids but was selected by MAb 5H11, which also selected the K434E escape mutant, suggesting that the footprint of 5H11 covers this entire area.…”

Section: Discussionmentioning

confidence: 92%

“…However, the antigenic characteristics of the NA of recent A(H7N9) viruses are poorly defined. A recent report showed that amino acids around the enzyme active center are critical for binding of an N9 MAb, 3c10-3 (21). In the present study, we characterize a panel of MAbs that bind to the NA of a reference A(H7N9) virus, A/Anhui/1/2013 (AH/13), and evaluate the in vitro functional attributes and in vivo effectiveness of selected N9 MAbs that bind to different antigenic domains.…”

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confidence: 98%

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Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Wan

Gao

et al. 2018

J Virol

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The fifth wave of A(H7N9) virus infection in China from 2016 to 2017 caused great concern due to the large number of individuals infected, the isolation of drug-resistant viruses, and the emergence of highly pathogenic strains. Antibodies against neuraminidase (NA) provide added benefit to hemagglutinin-specific immunity and may be important contributors to the effectiveness of A(H7N9) vaccines. We generated a panel of mouse monoclonal antibodies (MAbs) to identify antigenic domains on NA of the novel A(H7N9) virus and compared their functional properties. The loop formed in the region of residue 250 (250 loop) and the domain formed by the loops containing residues 370, 400, and 430 were identified as major antigenic regions. MAbs 1E8, 2F6, 10F4, and 11B2, which recognize these two antigenic domains, were characterized in depth. These four MAbs differ in their abilities to inhibit cleavage of small and large substrates (methyl-umbelliferylacetyl neuraminic acid [MU-NANA] and fetuin, respectively) in NA inhibition assays. 1E8 and 11B2 did not inhibit NA cleavage of either MU-NANA or fetuin, and 2F6 inhibited cleavage of fetuin alone, whereas 10F4 inhibited cleavage of both substrates. All four MAbs reduced the in vitro spread of viruses carrying either the wild-type N9 or N9 with antiviral-resistant mutations but to different degrees. These MAbs have different in vivo levels of effectiveness: 10F4 was the most effective in protecting mice against challenge with A(H7N9) virus, 2F6 was less effective, and 11B2 failed to protect BALB/c mice at the doses tested. Our study confirms that NA-specific antibodies can protect against A(H7N9) infection and suggests that in vitro properties can be used to rank antibodies with therapeutic potential. IMPORTANCEThe novel A(H7N9) viruses that emerged in China in 2013 continue to infect humans, with a high fatality rate. The most recent outbreak resulted in a larger number of human cases than previous epidemic waves. Due to the absence of a licensed vaccine and the emergence of drug-resistant viruses, there is a need to develop alternative approaches to prevent or treat A(H7N9) infection. We have made a panel of mouse monoclonal antibodies (MAbs) specific for neuraminidase (NA) of A(H7N9) viruses; some of these MAbs are effective in inhibiting viruses that are resistant to antivirals used to treat A(H7N9) patients. Binding avidity, inhibition of NA activity, and plaque formation correlated with the effectiveness of these MAbs to protect mice against lethal A(H7N9) virus challenge. This study identifies in vitro measures that can be used to predict the in vivo efficacy of NA-specific antibodies, providing a way to select MAbs for further therapeutic development.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 98%

See 1 more Smart Citation

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Wan

Gao

et al. 2018

J Virol

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“…Patients were characterized by rapidly progressive pneumonia, respiratory failure, acute respiratory distress syndrome and even with 35% fatality rate [2][3][4]. It has caused serious concerns for public health throughout the world.…”

Section: Introductionmentioning

confidence: 99%

Establish and Apply a Safe and Convenient Pseudovirus-Based Assay to Detect Neutralizing Antibodies against Influenza A (H7N9) Virus

Zhang

et al. 2017

Preprint

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Abstract:In March 2013, a novel avian influenza A H7N9 virus was emerged in China, which cause rapidly progressive pneumonia and with a high fatality rate. Serologic studies to evaluate neutralizing antibodies of infected patients and birds are invaluable tools for immunogenicity research of H7N9 and epidemiological investigation. Conventional neutralization assays are laborious and time-consuming which also hampered by biosafety requirement. In this study, We construct and produce pseudovirus bearing the full-length hemagglutinin (HA) of H7N9 virus in the Env-defective, luciferase-expressing HIV-1 backbone. The production of lentiviral pseudovirus was analysed by HA gene specific real-time reverse-transcription PCR, transmission electron microscopy (TEM), and Western Blot assay to prove the nucleic acid replication, the morphology of virus, and the expression of HA protein in pseudovirus. After that pseudovirus based inhibition assay was established to detect neutralizing antibodies of a panel of serum samples. Our results demonstrated that H7N9 pseudovirus which had single-cycle infection was generated. By comparing the neutralization antibody titers, pseudovirus based neutralization test could be recognized as an alternative of conventional microneutralization (MN). Hence, we conclude that it is possible to use pseudovirus inhibition assay to screen sera samples, as well as evaluate vaccine-induced neutralizing antibodies against H7N9 virus.

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“…The antihemagglutinin (anti-HA) antibodies play a dominant role in protection against HA-matched influenza virus, while anti-NA antibodies may also be protective in the case of mismatched HA (10)(11)(12)(13)(14)(15)(16). HA antibodies block viral attachment to the target cell surface, and if the virus enters into the endolysosome, these antibodies also block viral uncoating and release of the nucleoprotein into cytoplasm.…”

mentioning

confidence: 99%

Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after Natural Infection with Influenza A Viruses

Changsom

Jiang

Lerdsamran

et al. 2017

Clin Vaccine Immunol

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The kinetics, longevity, and breadth of antibodies to influenza virus neuraminidase (NA) in archival, sequential serum/plasma samples from influenza A virus (IAV) H5N1 infection survivors and from patients infected with the 2009 pandemic IAV (H1N1) virus were determined using an enzyme-linked lectin-based assay. The reverse-genetics-derived H4N1 viruses harboring a hemagglutinin (HA) segment from A/duck/Shan Tou/461/2000 (H4N9) and an NA segment derived from either IAV H5N1 clade 1, IAV H5N1 clade 2.3.4, the 2009 pandemic IAV (H1N1) (H1N1pdm), or A/Puerto Rico/8/1934 (H1N1) virus were used as the test antigens. These serum/ plasma samples were also investigated by microneutralization (MN) and/or hemagglutination inhibition (HI) assays. Neuraminidase-inhibiting (NI) antibodies against N1 NA of both homologous and heterologous viruses were observed in H5N1 survivors and H1N1pdm patients. H5N1 survivors who were never exposed to H1N1pdm virus developed NI antibodies to H1N1pdm NA. Seroconversion of NI antibodies was observed in 65% of the H1N1pdm patients at day 7 after disease onset, but an increase in titer was not observed in serum samples obtained late in infection. On the other hand, an increase in seroconversion rate with the HI assay was observed in the follow-up series of sera obtained on days 7, 14, 28, and 90 after infection. The study also showed that NI antibodies are broadly reactive, while MN and HI antibodies are more strain specific.

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An influenza A virus (H7N9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo

Cited by 33 publications

References 47 publications

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Comparison of the Efficacy of N9 Neuraminidase-Specific Monoclonal Antibodies against Influenza A(H7N9) Virus Infection

Establish and Apply a Safe and Convenient Pseudovirus-Based Assay to Detect Neutralizing Antibodies against Influenza A (H7N9) Virus

Kinetics, Longevity, and Cross-Reactivity of Antineuraminidase Antibody after Natural Infection with Influenza A Viruses

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