Distinct patterns of cellular immune response elicited by influenza non-adjuvanted and AS03-adjuvanted monovalent H1N1(pdm09) vaccine

The study aimed at identifying biomarkers of immune response elicited by non-adjuvanted-(NAV) and adjuvanted-(AV) H1N1(pdm09) vaccines. The results showed that despite both vaccines elicited similar levels of anti-H1N1 antibodies at day30 after vaccination, higher reactivity was observed in AV at da...

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Bibliographic Details
Published in:Antiviral research 2017-08, Vol.144, p.70-82
Main Authors: Giarola-Silva, Sarah, Coelho-dos-Reis, Jordana G.A., Mourão, Marina Moraes, Campi-Azevedo, Ana Carolina, Nakagaki Silva, Erick E., Luiza-Silva, Maria, Martins, Marina Angela, Silveira-Cassette, Amanda Cardoso de Oliveira, Batista, Maurício Azevedo, Peruhype-Magalhães, Vanessa, Antonelli, Lis Ribeiro do Valle, Leite Ribeiro, José Geraldo, Elói-Santos, Silvana Maria, Machado, Alexandre Vieira, Teixeira-Carvalho, Andréa, Martins-Filho, Olindo Assis, Araújo, Márcio Sobreira Silva
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - administration & dosage
Adult
alpha-Tocopherol - administration & dosage
AS03 adjuvant
Biomarker signature
Cytokines - biosynthesis
Cytokines - secretion
Drug Combinations
Female
H1N1 vaccine
Healthy Volunteers
Humans
Immune response
Immunity, Cellular
Influenza A Virus, H1N1 Subtype - immunology
Influenza Vaccines - administration & dosage
Influenza Vaccines - immunology
Male
Middle Aged
Polysorbates - administration & dosage
Squalene - administration & dosage
Treatment Outcome
Young Adult
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Summary:The study aimed at identifying biomarkers of immune response elicited by non-adjuvanted-(NAV) and adjuvanted-(AV) H1N1(pdm09) vaccines. The results showed that despite both vaccines elicited similar levels of anti-H1N1 antibodies at day30 after vaccination, higher reactivity was observed in AV at day180. While AV induced early changes in cell-surface molecules on monocytes, CD4+, CD8+ T-cells and B-cells, NAV triggered minor changes, starting later on at day3. Furthermore, AV induced a late and persistent increase in TLR gene expression after day3, except for tlr4, while NAV displayed earlier but transient tlr3/4/7/9 up-regulation. Contrasting with NAV, prominent chemokine gene expression (cxcl8,cxcl9,ccl5) and a broad spectrum up-regulation of plasmatic biomarkers (CXCL8,IL-6,IL-1β,IL-12,IL-10) was evident in AV, which showed a major involvement of TNF and IL-10. Similarly, AV induced a robust IL-10-modulated proinflammatory storm, with early and persistent involvement of TNF-α/IL-12/IFN-γ axis derived from NK-cells, CD4+ and CD8+ T-cells along with promiscuous production of IL-4/IL-5/IL-13. Conversely, NAV promotes a concise and restricted intracytoplasmic chemokine/cytokine response, essentially mediated by TNF-α and IL-4, with late IL-10 production by CD8+ T-cells. Systems biology approach underscored that AV guided the formation of an imbricate network characterized by a progressive increase in the number of neighborhood connections amongst innate and adaptive immunity. In AV, the early cross-talk between innate and adaptive immunity, followed by the triad NK/CD4+/CD8+ T-cells at day3, sponsored a later/robust biomarker network. These findings indicate the relevance of adjuvanted vaccination to orchestrate broad, balanced and multifactorial cellular immune events that lead ultimately to a stronger H1N1 humoral immunity. •Biomarkers of immune response elicited by non-adjuvanted and AS03-adjuvanted H1N1(pdm09) vaccines.•Higher long-lasting anti-H1N1 antibodies reactivity was observed AS03-adjuvanted vaccine.•AS03-adjuvanted vaccine orchestrates a broader, balanced and multifactorial cellular and humoral immune response.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2017.05.009