Induction of Broadly Cross-Reactive Stalk-Specific Antibody Responses to Influenza Group 1 and Group 2 Hemagglutinins by Natural H7N9 Virus Infection in Humans

Liu, Lu; Nachbagauer, Raffael; Zhu, Lingyan; Huang, Yang; Xie, Xinci; Jin, Songqing; Zhang, Anli; Wan, Yanmin; Hirsh, Ariana; Tian, Di; Shi, Xiaoling; Dong, Zhaoguang; Yuan, Songhua; Hu, Yunwen; Krammer, Florian; Zhang, Xiaoyan; Xu, Jianqing

doi:10.1093/infdis/jiw608

Cited by 33 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is considerable current interest in the conserved HA stalk as a target of broadly protective Abs and a potential basis for a universal influenza vaccine (26,27). It is well established that anti-stalk Ab production is favored when HA-immune individuals are exposed to relatively novel HAs, such as those of avian viruses or the 2009 pandemic virus (11,12,14,32,35). This reflects responses by stalk-specific MBCs with limited competition from MBCs reactive to the immunodominant HA head (9).…”

Section: Discussionmentioning

confidence: 99%

“…A larger pool of group 2 stalk-reactive MBCs could explain the greater level of protection against avian H7N9 infection in H3N2-imprinted subjects proposed by Gostic et al (29). The H7 head domain would be largely novel in H7N9-infected subjects, leaving the response of H7 stalk-reactive MBCs as the key determinant of the strength of early HA-specific Ab production and the severity of disease (32). This hypothesis is shown diagrammatically in Fig.…”

Section: Memory B Cell Expansion By Human Influenza Infectionmentioning

confidence: 90%

See 1 more Smart Citation

Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus

Tesini

Kanagaiah

Wang

et al. 2019

J Virol

Self Cite

106

View full text Add to dashboard Cite

Memory B cells (MBCs) are key determinants of the B cell response to influenza virus infection and vaccination, but the effect of different forms of influenza antigen exposure on MBC populations has received little attention. We analyzed peripheral blood mononuclear cells and plasma collected following human H3N2 influenza infection to investigate the relationship between hemagglutininspecific antibody production and changes in the size and character of hemagglutininreactive MBC populations. Infection produced increased concentrations of plasma IgG reactive to the H3 head of the infecting virus, to the conserved stalk, and to a broad chronological range of H3s consistent with original antigenic sin responses. H3-reactive IgG MBC expansion after infection included reactivity to head and stalk domains. Notably, expansion of H3 head-reactive MBC populations was particularly broad and reflected original antigenic sin patterns of IgG production. Findings also suggest that early-life H3N2 infection "imprints" for strong H3 stalk-specific MBC expansion. Despite the breadth of MBC expansion, the MBC response included an increase in affinity for the H3 head of the infecting virus. Overall, our findings indicate that H3-reactive MBC expansion following H3N2 infection is consistent with maintenance of response patterns established early in life, but nevertheless includes MBC adaptation to the infecting virus. IMPORTANCE Rapid and vigorous virus-specific antibody responses to influenza virus infection and vaccination result from activation of preexisting virus-specific memory B cells (MBCs).Understanding the effects of different forms of influenza virus exposure on MBC populations is therefore an important guide to the development of effective immunization strategies. We demonstrate that exposure to the influenza hemagglutinin via natural infection enhances broad protection through expansion of hemagglutinin-reactive MBC populations that recognize head and stalk regions of the molecule. Notably, we show that hemagglutinin-reactive MBC expansion reflects imprinting by early-life infection and that this might apply to stalkreactive, as well as to head-reactive, MBCs. Our findings provide experimental

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Memory B Cell Expansion By Human Influenza Infectionmentioning

confidence: 90%

Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus

Tesini

Kanagaiah

Wang

et al. 2019

J Virol

Self Cite

106

View full text Add to dashboard Cite

show abstract

“…It has become clear that exposure to viruses that differ significantly from those circulating can select responses to epitopes in both HA and NA that are shared between the incoming virus and the seasonal viruses in circulation, derived from the memory B cell population (42,43). While antibodies against new epitopes can also be generated, even in the elderly (33), it appears that they are initially at a disadvantage but may overtake and become dominant with time (44,45).…”

Section: Discussionmentioning

confidence: 99%

Broadly Inhibiting Antineuraminidase Monoclonal Antibodies Induced by Trivalent Influenza Vaccine and H7N9 Infection in Humans

Rijal

Wang

Tan

et al. 2020

J Virol

View full text Add to dashboard Cite

The majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time window, as seen in serological studies and the analysis of many murine monoclonal antibodies (MAbs). We report three broadly reactive human MAbs targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from humans over a period of a hundred years. The third antibody, isolated from a child with acute mild H7N9 infection, inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection. IMPORTANCE Antibodies to the influenza virus NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that of antibodies to HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive, with the ability to inhibit a wide spectrum of N1 NAs on viruses isolated between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy and that the efficacy of influenza vaccines could be enhanced by ensuring the appropriate content of NA antigen.

show abstract

“…John-Sebastian Eden, The University of Sydney, Sydney, NSW, Australia RSV is one of the most important causes of severe respiratory infection in infants and young children, as well as in older adults and the immunocompromised (Lee et al, 2013;Shi et al, 2017). However, understanding of the dynamics driving the on-going evolution and epidemiology of RSV transmission in humans is rather limited.…”

Section: Genomic and Epidemiological Dynamics Of Rsv In Australiamentioning

confidence: 99%

Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference

et al. 2018

View full text Add to dashboard Cite

The International Society for Influenza and other Respiratory Virus Diseases held its 5th Antiviral Group (isirv-AVG) Conference in Shanghai, China, in conjunction with the Shanghai Public Health Center and Fudan University from 14-16 June 2017. The three-day programme encompassed presentations on some of the clinical features, management, immune responses and virology of respiratory infections, including influenza A(H1N1)pdm09 and A(H7N9) viruses, MERS-CoV, SARS-CoV, adenovirus Type 80, enterovirus D68, metapneumovirus and respiratory syncytial virus (RSV). Updates were presented on several therapeutics currently in clinical trials, including influenza polymerase inhibitors pimodivir/JNJ6362387, S033188, favipiravir, monoclonal antibodies MHAA45449A and VIS410, and host directed strategies for influenza including nitazoxanide, and polymerase ALS-008112 and fusion inhibitors AK0529, GS-5806 for RSV. Updates were also given on the use of the currently licensed neuraminidase inhibitors. Given the location in China, there were also presentations on the use of Traditional Chinese Medicines. Following on from the previous conference, there were ongoing discussions on appropriate endpoints for severe influenza in clinical trials from regulators and clinicians, an issue which remains unresolved. The aim of this conference summary is to provide information for not only conference participants, but a detailed referenced review of the current status of clinical trials, and pre-clinical development of therapeutics and vaccines for influenza and other respiratory diseases for a broader audience.

show abstract

Induction of Broadly Cross-Reactive Stalk-Specific Antibody Responses to Influenza Group 1 and Group 2 Hemagglutinins by Natural H7N9 Virus Infection in Humans

Cited by 33 publications

References 35 publications

Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus

Broad Hemagglutinin-Specific Memory B Cell Expansion by Seasonal Influenza Virus Infection Reflects Early-Life Imprinting and Adaptation to the Infecting Virus

Broadly Inhibiting Antineuraminidase Monoclonal Antibodies Induced by Trivalent Influenza Vaccine and H7N9 Infection in Humans

Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference

Contact Info

Product

Resources

About