Antibody-Dependent Cell-Mediated Cytotoxicity to Hemagglutinin of Influenza A Viruses After Influenza Vaccination in Humans

Zhong, Weimin; Liu, Feng; Wilson, Jason R.; Holiday, Crystal; Li, Zhu-Nan; Bai, Yaohui; Tzeng, Wen-Pin; Stevens, James; York, Ian A.; Levine, Min Z.

doi:10.1093/ofid/ofw102

Cited by 25 publications

(23 citation statements)

References 39 publications

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“…These activities are strongly influenced by properties of the Fc domain, including isotype, subclass, and glycan, suggesting the importance of these factors in driving suitable effector function (Barouch et al , ; Gordon et al , ; Huang et al , ). Collectively, there is a rich history of such qualitative antibody characteristics serving as important correlates for control of natural infection and vaccine efficacy (Johnson et al , ; Osier et al , ; Gómez Román et al , ; Weber & Oxenius, ; Ackerman et al , ; Zhong et al , ; He et al , ; Jegaskanda et al , ; Li et al , ; Rouers et al , ). In general, in addition to better distinguishing observed differences in immunity, expanded biophysical analyses of antibody properties can provide a more refined understanding of characteristics important for potent responses and potentially how to improve them.…”

Section: Introductionmentioning

confidence: 99%

Antibody Fab‐Fc properties outperform titer in predictive models of SIV vaccine‐induced protection

Pittala

Bagley

Schwartz

et al. 2019

Molecular Systems Biology

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Characterizing the antigen‐binding and innate immune‐recruiting properties of the humoral response offers the chance to obtain deeper insights into mechanisms of protection than revealed by measuring only overall antibody titer. Here, a high‐throughput, multiplexed Fab‐Fc Array was employed to profile rhesus macaques vaccinated with a gp120‐ CD 4 fusion protein in combination with different genetically encoded adjuvants, and subsequently subjected to multiple heterologous simian immunodeficiency virus ( SIV ) challenges. Systems analyses modeling protection and adjuvant differences using Fab‐Fc Array measurements revealed a set of correlates yielding strong and robust predictive performance, while models based on measurements of response magnitude alone exhibited significantly inferior performance. At the same time, rendering Fab‐Fc measurements mathematically independent of titer had relatively little impact on predictive performance. Similar analyses for a distinct SIV vaccine study also showed that Fab‐Fc measurements performed significantly better than titer. These results suggest that predictive modeling with measurements of antibody properties can provide detailed correlates with robust predictive power, suggest directions for vaccine improvement, and potentially enable discovery of mechanistic associations.

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Section: Introductionmentioning

confidence: 99%

Antibody Fab‐Fc properties outperform titer in predictive models of SIV vaccine‐induced protection

Pittala

Bagley

Schwartz

et al. 2019

Molecular Systems Biology

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“…To understand the immunologic basis of protection against heterologous challenge, we attempted to test whether ADCC activity accounted for the cross-protection observed in ferrets. Although our laboratory has recently developed an improved ADCC NK cell activation assay utilizing human NK cell lines as effector cells (Zhong et al, 2016), the assay failed to detect H5-specific ADCC titers in ferret sera, most likely due to the incompatibility of the ferret immunoglobulin Fc region with human NK cell FcγRIIIa receptor (unpublished observation).…”

Section: Discussionmentioning

confidence: 99%

Stockpiled pre-pandemic H5N1 influenza virus vaccines with AS03 adjuvant provide cross-protection from H5N2 clade 2.3.4.4 virus challenge in ferrets

et al. 2017

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Avian influenza viruses, notably H5 subtype viruses, pose a continuous threat to public health due to their pandemic potential. In recent years, influenza virus H5 subtype split vaccines with novel oil-in-water emulsion based adjuvants (e.g. AS03, MF59) have been shown to be safe, immunogenic, and able to induce broad immune responses in clinical trials, providing strong scientific support for vaccine stockpiling. However, whether such vaccines can provide protection from infection with emerging, antigenically distinct clades of H5 viruses has not been adequately addressed. Here, we selected two AS03-adjuvanted H5N1 vaccines from the US national prepandemic influenza vaccine stockpile and assessed whether the 2004–05 vaccines could provide protection against a 2014 highly pathogenic avian influenza (HPAI) H5N2 virus (A/northern pintail/Washington/40964/2014), a clade 2.3.4.4 virus responsible for mass culling of poultry in North America. Ferrets received two doses of adjuvanted vaccine containing 7.5 μg of hemagglutinin (HA) from A/Vietnam/1203/2004 (clade 1) or A/Anhui/1/2005 (clade 2.3.4) virus either in a homologous or heterologous prime-boost vaccination regime. We found that both vaccination regimens elicited robust antibody responses against the 2004–05 vaccine viruses and could reduce virus-induced morbidity and viral replication in the lower respiratory tract upon heterologous challenge despite the low level of cross-reactive antibody titers to the challenge H5N2 virus. This study supports the value of existing stockpiled 2004–05 influenza H5N1 vaccines, combined with AS03-adjuvant for early use in the event of an emerging pandemic with H5N2-like clade 2.3.4.4 viruses.

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“…Nonetheless, it remains possible that these in vivo functions of TIV-sera may surface at a different stage of protective immunity or exhibit long-term impact. Indeed, recent studies have shown that ADCC-inducing Abs are readily detectable in normal human sera62, or increased following seasonal influenza vaccine as well as avian influenza vaccine6364. Therefore, further investigation utilizing specific gene-knockout mice will help clarify crucial in vivo CDC or ADCC functions of TIV-sera.…”

Section: Discussionmentioning

confidence: 99%

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease

Kim

Reber

Kumar

et al. 2016

Sci Rep

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The association of seasonal trivalent influenza vaccine (TIV) with increased infection by 2009 pandemic H1N1 (A(H1N1)pdm09) virus, initially observed in Canada, has elicited numerous investigations on the possibility of vaccine-associated enhanced disease, but the potential mechanisms remain largely unresolved. Here, we investigated if prior immunization with TIV enhanced disease upon A(H1N1)pdm09 infection in mice. We found that A(H1N1)pdm09 infection in TIV-immunized mice did not enhance the disease, as measured by morbidity and mortality. Instead, TIV-immunized mice cleared A(H1N1)pdm09 virus and recovered at an accelerated rate compared to control mice. Prior TIV immunization was associated with potent inflammatory mediators and virus-specific CD8 T cell activation, but efficient immune regulation, partially mediated by IL-10R-signaling, prevented enhanced disease. Furthermore, in contrast to suggested pathological roles, pre-existing non-neutralizing antibodies (NNAbs) were not associated with enhanced virus replication, but rather with promoted antigen presentation through FcR-bearing cells that led to potent activation of virus-specific CD8 T cells. These findings provide new insights into interactions between pre-existing immunity and pandemic viruses.

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Antibody-Dependent Cell-Mediated Cytotoxicity to Hemagglutinin of Influenza A Viruses After Influenza Vaccination in Humans

Cited by 25 publications

References 39 publications

Antibody Fab‐Fc properties outperform titer in predictive models of SIV vaccine‐induced protection

Antibody Fab‐Fc properties outperform titer in predictive models of SIV vaccine‐induced protection

Stockpiled pre-pandemic H5N1 influenza virus vaccines with AS03 adjuvant provide cross-protection from H5N2 clade 2.3.4.4 virus challenge in ferrets

Non-neutralizing antibodies induced by seasonal influenza vaccine prevent, not exacerbate A(H1N1)pdm09 disease

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