Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Inactivated Influenza Vaccines in Children

Black, Steven; Nicolay, Uwe; Vesikari, Timo; Knuf, Markus; Giudice, Giuseppe Del; Cioppa, Giovanni Della; Tsai, Theodore F.; Clemens, Ralf; Rappuoli, Rino

doi:10.1097/inf.0b013e3182367662

Cited by 299 publications

(239 citation statements)

References 17 publications

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“…Renewed interest in the role of non-neutralizing antibodies in protecting against influenza is related to the observation that the golden standard -the haemagglutination inhibition assay -does not always correlate with immune protection, which especially holds true for children (Black et al, 2011;Wrammert et al, 2011). Virus neutralization and Fc-mediated effector functions, such as ADCC, could provide complementary information (Black et al, 2011;Co et al, 2014;Jegaskanda et al, 2013b).…”

Section: Adcc Induction Pre-and Post-a(h1n1)2009 Infectionmentioning

confidence: 99%

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Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic

Mesman

Westerhuis

Hulscher

et al. 2016

Journal of General Virology

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Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

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Section: Adcc Induction Pre-and Post-a(h1n1)2009 Infectionmentioning

confidence: 99%

“…Virus neutralization and Fc-mediated effector functions, such as ADCC, could provide complementary information (Black et al, 2011;Co et al, 2014;Jegaskanda et al, 2013b).…”

Section: Adcc Induction Pre-and Post-a(h1n1)2009 Infectionmentioning

confidence: 99%

Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic

Mesman

Westerhuis

Hulscher

et al. 2016

Journal of General Virology

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“…Though a recent paper by Ng et al estimated that HAI titers of 1:40 against A(H1N1)pdm09 and B(Victoria lineage) were associated with 48% [95% confidence interval (CI) 30-62%] and 55% [95% CI 32-70%] protection against polymerase chain reaction (PCR)-confirmed infection in children (17), other studies suggest that HAI titers should not be used alone to assess vaccine efficacy, especially in high-risk groups such as children and older adults. Black et al found that in children, who have less prior experience with influenza virus infection or vaccination, a higher titer of 1:110 was associated with the conventional 50% protective rate and that the 1:40 titer was associated with only 22% protection (1). In a study by Ohmit et al, H3N2 influenza cases had lower pre-and post-vaccination mean HAI titers than noncases, but a small number of cases had ''protective'' HAI antibodies ranging from 64 to 3,028.…”

Section: Introductionmentioning

confidence: 99%

Relationship of Preexisting Influenza Hemagglutination Inhibition, Complement-Dependent Lytic, and Antibody-Dependent Cellular Cytotoxicity Antibodies to the Development of Clinical Illness in a Prospective Study of A(H1N1)pdm09 Influenza in Children

Terajima

Thomas

et al. 2014

Viral Immunology

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The hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza. However, recent studies have highlighted the limitations on the use of the HAI titer as a correlate in at-risk populations such as children and older adults. In addition to the neutralization of cell-free virus by antibodies to hemagglutinin and interference of virus release from infected cells by antibodies to neuraminidase, influenza virus-specific antibodies specifically can bind to infected cells and lyse virus-infected cells through the activation of complement or natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL). We evaluated preexisting HAI, CDL, and ADCC antibodies in young children enrolled in a prospective cohort study of dengue during the epidemic with influenza A(H1N1)pdm09 virus to determine associations between preexisting antibodies and the occurrence of clinical or subclinical influenza virus infection. Though both preexisting HAI and CDL antibodies were associated with protection against clinical influenza, our data suggested that CDL was not a better correlate than HAI. We found that ADCC antibodies behaved differently from HAI and CDL antibodies. Unlike HAI and CDL antibodies, preexisting ADCC antibodies did not correlate with protection against clinical influenza. In fact, ADCC antibodies were detected more frequently in the clinical influenza group than the subclinical group. In addition, in contrast to HAI and CDL antibodies, HAI and the ADCC antibodies titers did not correlate. We also found that ADCC, but not CDL or HAI antibodies, positively correlated with the ages of the children.

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“…Whether the correlates established in these challenge studies5 can be transferred to these situations has not been established. For example, one study identified that in children, an HI titre >1:110 would predict 50% of clinical protection and a titre of 1:330 would predict 80% of protection 11. A second study could not consistently predict protection with HI titres in healthy adults,8 and in older adults, it has been suggested that cell‐mediated immunity (CMI) rather than humoral immunity would be associated with protection 12.…”

Section: Serological Correlates Of Protection: Moving Away From the Ementioning

confidence: 99%

A review of the changes to the licensing of influenza vaccines in Europe

Wijnans

Voordouw

2015

Influenza Resp Viruses

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In 2014, the European Committee for Medicinal Products for Human Use (CHMP) published a draft regulatory guideline for the evaluation of influenza vaccines. Following a public consultation round, the final guidance will be published in the near future. Here, we highlight the main changes in the clinical section in this guideline and discuss the background to these changes and whether the new consolidated guidance document can be expected to achieve a better understanding of the performance of seasonal, zoonotic and pandemic influenza vaccines during the regulatory licensing process. The new influenza guideline reflects a changed approach to the regulatory assessment of influenza vaccines, resulting in the abolition of serological criteria, known as the CHMP criteria, which have been the mainstay for evaluating the influenza vaccine immunogenicity for several decades. The new guideline adopts a more diversified approach to the measurement and reporting of the immune response to influenza vaccines and sets a requirement to conduct clinical outcome trials in young children. Importantly, more emphasis is placed on the post‐licensure monitoring of the benefit risk of influenza vaccines, including a request for continuous monitoring of efficacy and enhanced safety surveillance. Despite the improvements these new requirements will expectedly bring to the regulatory assessment of influenza vaccines, major challenges remain which cannot be overcome by new guidance alone. Ongoing initiatives in which academia, manufacturers, public health institutes and regulators work together to address these challenges are central to the development of robust tools to evaluate and monitor performance of influenza vaccines in the future.

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Hemagglutination Inhibition Antibody Titers as a Correlate of Protection for Inactivated Influenza Vaccines in Children

Cited by 299 publications

References 17 publications

Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic

Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic

Relationship of Preexisting Influenza Hemagglutination Inhibition, Complement-Dependent Lytic, and Antibody-Dependent Cellular Cytotoxicity Antibodies to the Development of Clinical Illness in a Prospective Study of A(H1N1)pdm09 Influenza in Children

A review of the changes to the licensing of influenza vaccines in Europe

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