Evaluation of the immune response of a H7N9 candidate vaccine virus derived from the fifth wave A/Guangdong/17SF003/2016

Dong, Jinhua; Chen, Peihai; Wang, Yang; Lv, Yunhua; Xiao, Ji; Li, Qinming; Li, Zhixia; Zhang, Beiwu; Niu, Xuefeng; Li, Chufang; Pan, Weiqi; Chen, Ling

doi:10.1016/j.antiviral.2020.104776

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…For example, in Italy, five amino acid substitutions (G133E, A151T, G177V, Q201H, and T112A) in H7N3 viruses during 2002-2004 were identified in the antigenic variant and parent strains, and four of them reside in ABSs [128]. Of interest, for H7N9 viruses, although there was a greater than 4-fold reduction in HI titers between the viruses in the fifth wave and those in the first wave [129], the in vitro and in vivo studies both showed that the heterologous antisera can neutralize virus infection [130]. Further analyses showed that the reduction of the HI titers is predominantly driven by the increased receptor-binding avidity determined by the amino acid substitution L226Q to red blood cells [131].…”

Section: Antigenic Drift Of Avian Influenza Viruses (Aivs)mentioning

confidence: 99%

Antigenic characterization of influenza and SARS-CoV-2 viruses

2021

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Antigenic characterization of emerging and re-emerging viruses is necessary for the prevention of and response to outbreaks, evaluation of infection mechanisms, understanding of virus evolution, and selection of strains for vaccine development. Primary analytic methods, including enzyme-linked immunosorbent/lectin assays, hemagglutination inhibition, neuraminidase inhibition, micro-neutralization assays, and antigenic cartography, have been widely used in the field of influenza research. These techniques have been improved upon over time for increased analytical capacity, and some have been mobilized for the rapid characterization of the SARS-CoV-2 virus as well as its variants, facilitating the development of highly effective vaccines within 1 year of the initially reported outbreak. While great strides have been made for evaluating the antigenic properties of these viruses, multiple challenges prevent efficient vaccine strain selection and accurate assessment. For influenza, these barriers include the requirement for a large virus quantity to perform the assays, more than what can typically be provided by the clinical samples alone, cell- or egg-adapted mutations that can cause antigenic mismatch between the vaccine strain and circulating viruses, and up to a 6-month duration of vaccine development after vaccine strain selection, which allows viruses to continue evolving with potential for antigenic drift and, thus, antigenic mismatch between the vaccine strain and the emerging epidemic strain. SARS-CoV-2 characterization has faced similar challenges with the additional barrier of the need for facilities with high biosafety levels due to its infectious nature. In this study, we review the primary analytic methods used for antigenic characterization of influenza and SARS-CoV-2 and discuss the barriers of these methods and current developments for addressing these challenges.

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Section: Antigenic Drift Of Avian Influenza Viruses (Aivs)mentioning

confidence: 99%

Antigenic characterization of influenza and SARS-CoV-2 viruses

2021

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“…This study investigated the antigenic differences of selected H7 panel influenza HA proteins. Since most available H7 HA sequences originated from major human infections, the selected H7 panel strains were similar with the list of candidate vaccine viruses (CVVs) from the WHO (10). There was a high similarity of amino acid sequences in the putative HA antigenic sites (Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…For prompt production and distribution of vaccines during a pandemic emergency, the World Health Organization (WHO) has stockpiled candidate vaccine viruses (CVVs) for all H7 influenza viruses (9). However, the antigenic differences of stockpiled CVVs have not been investigated, especially for the H7N9 viruses isolated after 2016 (10). To prepare for the next H7 influenza virus epidemics, it is imperative to identify the antigenic differences of co-circulating H7 HA proteins and clarify the target coverage by the antigen.…”

Section: Introductionmentioning

confidence: 99%

Hemagglutination Inhibition (HAI) Antibody Landscapes after Vaccination with diverse H7 hemagglutinin (HA) proteins

Jang

Ross

2021

Preprint

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BackgroundA systemic evaluation of the antigenic differences of the H7 influenza hemagglutinin (HA) proteins, especially for the viruses isolated after 2016, are limited. The purpose of this study was to investigate the antigenic differences of major H7 strains with an ultimate aim to discover H7 HA proteins that can elicit protective receptor-blocking antibodies against co-circulating H7 influenza strains.MethodA panel of nine H7 influenza strains were selected from 3,633 H7 HA amino acid sequences identified over the past two decades (2000-2018). The sequences were expressed on the surface of virus like particles (VLPs) and used to vaccinate C57BL/6 mice. Serum samples were collected and tested for hemagglutination-inhibition (HAI) activity. The vaccinated mice were challenged with lethal dose of H7N9 virus, A/Anhui/1/2013.ResultsVLPs expressing the H7 HA antigens elicited broadly reactive antibodies each of the selected H7 HAs, except the A/Turkey/Italy/589/2000 (Italy/00) H7 HA. A putative glycosylation due to an A169T substitution in antigenic site B was identified as a unique antigenic profile of Italy/00. Introduction of the putative glycosylation site (H7 HA-A169T) significantly altered the antigenic profile of HA of the A/Anhui/1/2013 (H7N9) strain.ConclusionThis study identified key amino acid mutations that result in severe vaccine mismatches for future H7 epidemics. Future universal influenza vaccine candidates will need to focus on viral variants with these key mutations.

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“…with the potent cross-reactive neutralizing antibodies and in vivo cross-protection between them (14). We also found that the increased HA receptor-binding avidity to red blood cells (RBCs) was responsible for the insensitive detection of the HI antibody titers against GD/16 (14).…”

Section: Figmentioning

confidence: 91%

L226Q Mutation on Influenza H7N9 Virus Hemagglutinin Increases Receptor-Binding Avidity and Leads to Biased Antigenicity Evaluation

Wang

Niu

et al. 2020

J Virol

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Since the first outbreak in 2013, the influenza A (H7N9) virus has continued emerging and caused over five epidemic waves. Suspected antigenic changes of the H7N9 virus based on hemagglutination inhibition (HI) assay during the fifth outbreak have prompted the update of H7N9 candidate vaccine viruses (CVVs). In this study, we comprehensively compared the serological cross-reactivity induced by the hemagglutinins (HAs) of the earlier CVV A/Anhui/1/2013 (H7/AH13) and the updated A/Guangdong/17SF003/2016 (H7/GD16). We found that although H7/GD16 showed poor HI cross-reactivity to immune sera from mice and rhesus macaques vaccinated with either H7/AH13 or H7/GD16, the cross-reactive neutralizing antibodies between H7/AH13 and H7/GD16 were comparably high. Passive transfer of H7/AH13 immune sera also provided complete protection against the lethal challenge of H7N9/GD16 virus in mice. Analysis of amino acid mutations in the HAs between H7/AH13 and H7/GD16 revealed that L226Q substitution increases the HA binding avidity to sialic acid receptors on red blood cells, leading to decreased HI titers against viruses containing HA Q226 and thus resulted in a biased antigenic evaluation based on HI assay. These results suggest that amino acids located in the receptor-binding site could mislead the evaluation of antigenic variation by solely impact on the receptor-binding avidity to red blood cells without genuine contribution to antigenic drift. Our study highlights that viral receptor-binding avidity and combination of multiple serological assays should be taken into consideration in evaluating and selecting a candidate vaccine virus of H7N9 and other subtypes of influenza viruses. IMPORTANCE The HI assay is a standard method for profiling the antigenic characterization of influenza viruses. Suspected antigenic changes based on HI divergency in H7N9 viruses during the 2016-2017 wave prompted the recommendation of new H7N9 candidate vaccine viruses (CVVs). In this study, we found that the L226Q substitution in HA of A/Guangdong/17SF003/2016 (H7/GD16) increased the viral receptor-binding avidity to red blood cells with no impact on the antigenicity of H7N9 virus. Although immune sera raised by an earlier vaccine strain (H7/AH13) showed poor HI titers against H7/GD16, the H7/AH13 immune sera had potent cross-neutralizing antibody titers against H7/GD16 and could provide complete passive protection against H7N9/GD16 virus challenge in mice. Our study highlights that receptor-binding avidity might lead to biased antigenic evaluation by using HI assay. Other serological assays, such as MN assay, should be considered as a complementary indicator for analysis of antigenic variation and selection of influenza CVVs.

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Evaluation of the immune response of a H7N9 candidate vaccine virus derived from the fifth wave A/Guangdong/17SF003/2016

Cited by 11 publications

References 41 publications

Antigenic characterization of influenza and SARS-CoV-2 viruses

Antigenic characterization of influenza and SARS-CoV-2 viruses

Hemagglutination Inhibition (HAI) Antibody Landscapes after Vaccination with diverse H7 hemagglutinin (HA) proteins

L226Q Mutation on Influenza H7N9 Virus Hemagglutinin Increases Receptor-Binding Avidity and Leads to Biased Antigenicity Evaluation

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