Microneutralization Assay Titres Correlate with Protection against Seasonal Influenza H1N1 and H3N2 in Children

Verschoor, Chris P.; Singh, Pardeep; Russell, Margaret L.; Bowdish, Dawn M. E.; Brewer, Angela; Cyr, Louis; Ward, Brian J.; Loeb, Mark

doi:10.1371/journal.pone.0131531

Cited by 71 publications

(70 citation statements)

References 15 publications

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“…The functional nature of the Abs induced by QVLP vaccination was confirmed by the MN results that correlated well overall with HI titers. Although occasional discrepancies between HI and MN results have been reported and there is some evidence that MN results may be more sensitive predictors of protection for children[41], our data suggest that the Abs induced months in the 15 g group. At all QVLP doses, antibody persistence was generally greater for influenza A than the B strains.…”

contrasting

confidence: 46%

A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

Pillet

Aubin

Trépanier

et al. 2016

Clinical Immunology

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122

101

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Recent issues regarding efficacy of influenza vaccines have re-emphasized the need of new approaches to face this major public health issue. In a phase 1-2 clinical trial, healthy adults received one intramuscular dose of a seasonal influenza plant-based quadrivalent virus-like particle (QVLP) vaccine or placebo. The hemagglutination inhibition (HI) titers met all the European licensure criteria for the type A influenza strains at the 3μg/strain dose and for all four strains at the higher dosages 21days after immunization. High HI titers were maintained for most of the strains 6months after vaccination. QVLP vaccine induced a substantial and sustained increase of hemagglutinin-specific polyfunctional CD4 T cells, mainly transitional memory and TEMRA effector IFN-γ(+) CD4 T cells. A T cells cross-reactive response was also observed against A/Hong-Kong/1/1968 H3N2 and B/Massachusetts/2/2012. Plant-based QVLP offers an attractive alternative manufacturing method for producing effective and HA-strain matching seasonal influenza vaccines.

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contrasting

confidence: 46%

A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

Pillet

Aubin

Trépanier

et al. 2016

Clinical Immunology

Self Cite

122

101

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“…HI and microneutralization titers were determined using routine methods, as described previously (34)(35)(36)(37). The microneutralization assay has been shown to have better sensitivity in detecting serum antibodies than HI assays, and findings correlate with protection against seasonal influenza (38)(39)(40). However, HI assays offer several advantages, i.e., they are relatively simple and inexpensive to perform and are widely used around the world, allowing easier comparisons and perhaps standardization (41).…”

Section: Methodsmentioning

confidence: 99%

Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

Epps

Tumpey

Pearce

et al. 2017

Clin Vaccine Immunol

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Both preexisting immunity to influenza and age have been shown to be correlates of influenza vaccine responses. Frailty, an indicator of functional impairment in older adults, was also shown in one study to predict lower influenza vaccine responses among nonveterans. In the current study, we aimed to determine the associations between frailty, preexisting immunity, and immune responses to influenza vaccine among older veterans. We studied 117 subjects (age range, 62 to 95 years [median age, 81 years]), divided into three cohorts based on the Fried frailty test, i.e., nonfrail (NF) (n ϭ 23 [median age, 68 years]), prefrail (n ϭ 50 [median age, 80 years]), and frail (n ϭ 44 [median age, 82 years]), during the 2010-2011 and 2011-2012 influenza seasons. Subjects received the seasonal trivalent inactivated influenza vaccine, and baseline and postvaccination samples were obtained. Anti-influenza humoral immunity, as measured by hemagglutination inhibition (HI) and microneutralization assays, was measured for influenza B, A(H1N1)pdm09, and A(H3N2) viruses. Postvaccination titers were not different between frail and NF subjects overall in this older subset of veterans. However, preexisting HI titers were strongly correlated with postvaccination titers among all functional status groups. When microneutralization titers were compared, the association between preexisting immunity and vaccine responses varied by frailty status, with the strongest correlation being observed for the NF group. In conclusion, preexisting immunity rather than frailty appeared to predict postvaccination titers in this older veteran cohort.

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“…But as the current work will underscore, the antigenic effect of mutating a residue to one amino acid can be poorly predictive of the effects of mutating the same residue to another amino acid. Furthermore, the difficulty in individually generating and testing large numbers of viral variants means that such studies often use simpler assays (e.g., hemagglutination-inhibition, pseudovirus neutralization, or protein binding) that can be imperfect surrogates for how well a mutation enables a replication-competent virus to escape antibody neutralization [16–18]. …”

Section: Introductionmentioning

confidence: 99%

Complete mapping of viral escape from neutralizing antibodies

2017

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Identifying viral mutations that confer escape from antibodies is crucial for understanding the interplay between immunity and viral evolution. We describe a high-throughput approach to quantify the selection that monoclonal antibodies exert on all single amino-acid mutations to a viral protein. This approach, mutational antigenic profiling, involves creating all replication-competent protein variants of a virus, selecting with antibody, and using deep sequencing to identify enriched mutations. We use mutational antigenic profiling to comprehensively identify mutations that enable influenza virus to escape four monoclonal antibodies targeting hemagglutinin, and validate key findings with neutralization assays. We find remarkable mutation-level idiosyncrasy in antibody escape: for instance, at a single residue targeted by two antibodies, some mutations escape both antibodies while other mutations escape only one or the other. Because mutational antigenic profiling rapidly maps all mutations selected by an antibody, it is useful for elucidating immune specificities and interpreting the antigenic consequences of viral genetic variation.

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Microneutralization Assay Titres Correlate with Protection against Seasonal Influenza H1N1 and H3N2 in Children

Cited by 71 publications

References 15 publications

A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

Complete mapping of viral escape from neutralizing antibodies

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