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Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

ABSTRACT: A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

SUBMITTER: Vaccari M

PROVIDER: S-EPMC5916782 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

Vaccari Monica M Gordon Shari N SN Fourati Slim S Schifanella Luca L Liyanage Namal P M NP Cameron Mark M Keele Brandon F BF Shen Xiaoying X Tomaras Georgia D GD Billings Erik E Rao Mangala M Chung Amy W AW Dowell Karen G KG Bailey-Kellogg Chris C Brown Eric P EP Ackerman Margaret E ME Vargas-Inchaustegui Diego A DA Whitney Stephen S Doster Melvin N MN Binello Nicolo N Pegu Poonam P Montefiori David C DC Foulds Kathryn K Quinn David S DS Donaldson Mitzi M Liang Frank F Loré Karin K Roederer Mario M Koup Richard A RA McDermott Adrian A Ma Zhong-Min ZM Miller Christopher J CJ Phan Tran B TB Forthal Donald N DN Blackburn Matthew M Caccuri Francesca F Bissa Massimiliano M Ferrari Guido G Kalyanaraman Vaniambadi V Ferrari Maria G MG Thompson DeVon D Robert-Guroff Marjorie M Ratto-Kim Silvia S Kim Jerome H JH Michael Nelson L NL Phogat Sanjay S Barnett Susan W SW Tartaglia Jim J Venzon David D Stablein Donald M DM Alter Galit G Sekaly Rafick-Pierre RP Franchini Genoveffa G

Nature medicine 20160530 7

A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in ...[more]

PMID: 27239761

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Project description:Introduction Enzootic pneumonia still causes major economic losses to the intensive pig production. Vaccination against its primary pathogen, Mycoplasma hyopneumoniae, is carried out worldwide to control the disease and minimize clinical signs and performance losses. Nonetheless, the effects of both infection with, and vaccination against Mycoplasma hyopneumoniae on the innate and adaptive immune responses remain largely unknown. Therefore, we conducted a study in which piglets were injected once with a commercial bacterin V1 or V2, or the adjuvant of V1 (A) to investigate their effect on local, innate and adaptive immune responses. Methods Three weeks after vaccination, piglets were challenge infected with M. hyopneumoniae and euthanized four weeks later to assess vaccine efficacy via macroscopic and microscopic evaluation of lung lesions. Blood and broncho-alveolar lavage fluid (BAL) samples were collected to measure antibody responses, cellular immunity, BAL cytokine levels and BAL M. hyopneumoniae DNA load as well as cytokine secretion by monocytes. Results After vaccination, proliferation of antigen-specific CD3+ T cells and a higher percentage of TNF-α+ CD8+, and TNF-α+ and TNF-α+IFN-γ+ CD4+CD8+ T cells was seen in V1, while proliferation of or a significant increase in cytokine production by different T cell subsets could not be observed for animals from V2. Interestingly, LPS-stimulated blood monocytes from V1 and A secreted less IL-10 on D7. After challenge, higher levels of IgA, more IL-10 and less IL-1β was detected in BAL from V1, which was not observed in V2. Animals from A had significantly more IL-17A in BAL. The macroscopic lung lesion score and the M. hyopneumoniae DNA load at euthanasia was lower in V1, but the microscopic lung lesion score was lower in both vaccinated groups. Discussion In conclusion, these results indicate that the two commercial bacterins induced different local and adaptive immune responses, that the adjuvant alone can reduce anti-inflammatory innate immune responses, and that both vaccines had a different efficacy to reduce Mycoplasma-like lung lesions and M. hyopneumoniae DNA load in the lung.

Dataset Information

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

Publications

Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

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