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Adjuvanted influenza vaccine dynamics.

ABSTRACT: Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. In particular, squalene-containing adjuvants have been observed to induce enhanced antibody responses, as well as having an influence on cross-reactive immunity. To explore the effects of adjuvanted vaccine formulations on antibody response and their relation to protein-specific immunity, we propose different mathematical models of antibody production dynamics in response to influenza vaccination. Data from ferrets immunized with commercial H1N1pdm09 vaccine antigen alone or formulated with different adjuvants was instrumental to adjust model parameters. While the affinity maturation process complexity is abridged, the proposed model is able to recapitulate the essential features of the observed dynamics. Our numerical results suggest that there exists a qualitative shift in protein-specific antibody response, with enhanced production of antibodies targeting the NA protein in adjuvanted versus non-adjuvanted formulations, in conjunction with a protein-independent boost that is over one order of magnitude larger for squalene-containing adjuvants. Furthermore, simulations predict that vaccines formulated with squalene-containing adjuvants are able to induce sustained antibody titers in a robust way, with little impact of the time interval between immunizations.

SUBMITTER: Parra-Rojas C

PROVIDER: S-EPMC6329778 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Adjuvanted influenza vaccine dynamics.

Parra-Rojas César C Messling Veronika von VV Hernandez-Vargas Esteban A EA

Scientific reports 20190111 1

Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. In particular, squalene-containing adjuvants have been observed to induce enhanced antibody responses, as well as having an influence on cross-reactive immunity. To explore the effects of adjuvanted vaccine formulations on antibody response and their relation to ...[more]

PMID: 30635599

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Project description:Because many Aboriginal Canadians had severe cases of pandemic (H1N1) 2009 influenza, they were given priority access to vaccine. However, it was not known if the single recommended dose would adequately protect people at high risk, prompting our study to assess responses to the vaccine among Aboriginal Canadians.We enrolled First Nations and Métis adults aged 20-59 years in our prospective cohort study. Participants were given one 0.5-mL dose of ASO3-adjuvanted pandemic (H1N1) 2009 vaccine (Arepanrix, GlaxoSmithKline Canada). Blood samples were taken at baseline and 21-28 days after vaccination. Paired sera were tested for hemagglutination-inhibiting antibodies at a reference laboratory. To assess vaccine safety, we monitored the injection site symptoms of each participant for seven days. We also monitored patients for general symptoms within 7 days of vaccination and any use of the health care system for 21-28 days after vaccination.We enrolled 138 participants in the study (95 First Nations, 43 Métis), 137 of whom provided all safety data and 136 of whom provided both blood samples. First Nations and Métis participants had similar characteristics, including high rates of chronic health conditions (74.4%-76.8%). Pre-existing antibody to the virus was detected in 34.3% of the participants, all of whom boosted strongly with vaccination (seroprotection rate [titre ? 40] 100%, geometric mean titre 531-667). Participants with no pre-existing antibody also responded well. Fifty-eight of 59 (98.3%) First Nations participants showed seroprotection and a geometric mean titre of 353.6; all 30 Métis participants with no pre-existing antibody showed seroprotection and a geometric mean titre of 376.2. Pain at the injection site and general symptoms frequently occurred but were short-lived and generally not severe, although three participants (2.2%) sought medical attention for general symptoms.First Nations and Métis adults responded robustly to ASO3-adjuvanted pandemic (H1N1) 2009 vaccine. Virtually all participants showed protective titres, including those with chronic health conditions.

Project description:BackgroundAdjuvant formulations are critical components of modern vaccines based on recombinant proteins, which are often poorly immunogenic without additional immune stimulants. Oil-in-water emulsions comprise an advanced class of vaccine adjuvants that are components of approved seasonal and pandemic influenza vaccines. However, few reports have been published that systematically evaluate the in vitro stability and in vivo adjuvant effects of different emulsion components.ObjectivesTo evaluate distinct classes of surfactants, oils, and excipients, for their effects on emulsion particle size stability, antigen structural interactions, and in vivo activity when formulated with a recombinant H5N1 antigen.MethodsEmulsions were manufactured by high pressure homogenization and characterized alone or in the presence of vaccine antigen by dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity, electron microscopy, fluorescence spectroscopy, and SDS-PAGE. In vivo vaccine activity in the murine model was characterized by measuring antibody titers, antibody-secreting plasma cells, hemagglutination inhibition titers, and cytokine production.ResultsWe demonstrate that surfactant class and presence of additional excipients are not critical for biological activity, whereas oil structure is crucial. Moreover, we report that simplified two-component emulsions appear more stable by particle size than more complex formulations.Finally, differences in antigen structural interactions with the various emulsions do not appear to correlate with in vivo activity.ConclusionsOil-in-water emulsions can significantly enhance antibody and cellular immune responses to a pandemic influenza antigen. The dramatic differences in adjuvant activity between squalene-based emulsion and medium chain triglyceride-based emulsion are due principally to the biological activity of the oil composition rather than physical interactions of the antigen with the emulsion.

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Adjuvanted influenza vaccine dynamics.

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Adjuvanted influenza vaccine dynamics.

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