ArticleFrontiers in immunology2021
Administration of Multivalent Influenza Virus Recombinant Hemagglutinin Vaccine in Combination-Adjuvant Elicits Broad Reactivity Beyond the Vaccine Components.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- mRNA Vaccines for Influenza: Hope for a Universal Vaccine?BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- The Squalene Oil-in-Water Nanoemulsion Vaccine Carrier AddaVax Potentiates TLR-Induced B-Cell Responses.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2026Article
- Comparative evaluation of 5 combination adjuvants on immunogenicity and efficacy of approved seasonal influenza vaccines.NPJ vaccines · 2026Article
- Detection and Validation of Influenza Virus Hemagglutinin Specific, Cross-Reactive, and Heteroclitic B Cells Induced by a Combination Vaccine Adjuvant.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2025Article
- Co-Delivery of Multiple Toll-Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy.Advanced healthcare materials · 2025Article
- Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.ImmunoHorizons · 2025Article
- Broad antibody and T cell responses to Ebola, Sudan, and Bundibugyo ebolaviruses using mono- and multi-valent adjuvanted glycoprotein vaccines.Antiviral research · 2024Article
- Insights into vaccines for elderly individuals: from the impacts of immunosenescence to delivery strategies.NPJ vaccines · 2024Review
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- Engineering Protein Nanoparticles Functionalized with an ImmunodominantBioconjugate chemistry · 2023Article
- Protein Nanoparticle-Mediated Delivery of Recombinant Influenza Hemagglutinin Enhances Immunogenicity and Breadth of the Antibody Response.ACS infectious diseases · 2023Article
- Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice.Vaccines · 2023Article
- Multivalent vaccines demonstrate immunogenicity and protect againstFrontiers in immunology · 2023Article
- How aging impacts vaccine efficacy: known molecular and cellular mechanisms and future directions.Trends in molecular medicine · 2022Review
- A Protein Microarray-Based Respiratory Viral Antigen Testing Platform for COVID-19 Surveillance.Biomedicines · 2022Article
- Microneedle Delivery of an Adjuvanted Microparticulate Vaccine Induces High Antibody Levels in Mice Vaccinated against Coronavirus.Vaccines · 2022Article
- Magnitude and breadth of antibody cross-reactivity induced by recombinant influenza hemagglutinin trimer vaccine is enhanced by combination adjuvants.Scientific reports · 2022Article
- Supramolecular Nanostructures for Vaccines.Biomimetics (Basel, Switzerland) · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Combining variant antigens into a multivalent vaccine is a traditional approach used to provide broad coverage against antigenically variable pathogens, such as polio, human papilloma and influenza viruses. However, strategies for increasing the breadth of antibody coverage beyond the vaccine are not well understood, but may provide more anticipatory protection. Influenza virus hemagglutinin (HA) is a prototypic variant antigen. Vaccines that induce HA-specific neutralizing antibodies lose efficacy as amino acid substitutions accumulate in neutralizing epitopes during influenza virus evolution. Here we studied the effect of a potent combination adjuvant (CpG/MPLA/squalene-in-water emulsion) on the breadth and maturation of the antibody response to a representative variant of HA subtypes H1, H5 and H7. Using HA protein microarrays and antigen-specific B cell labelling, we show when administered individually, each HA elicits a cross-reactive antibody profile for multiple variants within the same subtype and other closely-related subtypes (homosubtypic and heterosubtypic cross-reactivity, respectively). Despite a capacity for each subtype to induce heterosubtypic cross-reactivity, broader coverage was elicited by simply combining the subtypes into a multivalent vaccine. Importantly, multiplexing did not compromise antibody avidity or affinity maturation to the individual HA constituents. The use of adjuvants to increase the breadth of antibody coverage beyond the vaccine antigens may help future-proof vaccines against newly-emerging variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.