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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2016 ; 11
(6
): e0157887
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Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic
Inhaled Aerosol and Intra-Nasal Routes of Infection
#MMPMID27311020
Marriott AC
; Dennis M
; Kane JA
; Gooch KE
; Hatch G
; Sharpe S
; Prevosto C
; Leeming G
; Zekeng EG
; Staples KJ
; Hall G
; Ryan KA
; Bate S
; Moyo N
; Whittaker CJ
; Hallis B
; Silman NJ
; Lalvani A
; Wilkinson TM
; Hiscox JA
; Stewart JP
; Carroll MW
PLoS One
2016[]; 11
(6
): e0157887
PMID27311020
show ga
Non-human primates are the animals closest to humans for use in influenza A virus
challenge studies, in terms of their phylogenetic relatedness, physiology and
immune systems. Previous studies have shown that cynomolgus macaques (Macaca
fascicularis) are permissive for infection with H1N1pdm influenza virus. These
studies have typically used combined challenge routes, with the majority being
intra-tracheal delivery, and high doses of virus (> 107 infectious units). This
paper describes the outcome of novel challenge routes (inhaled aerosol,
intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming
units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and
sero-conversion were detected in all four challenge groups, although the disease
was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal
cavity. A low dose (103 plaque forming units) did not lead to detectable
infectious virus shedding, but a 1000-fold higher dose led to virus shedding in
all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal
challenge routes led to infections throughout the respiratory tract, although
shedding from the nasal cavity was less reproducible between animals compared to
the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges
induced a transient lymphopaenia, similar to that observed in influenza-infected
humans, and greater virus-specific cellular immune responses in the blood were
observed in these groups in comparison to the intra-nasal challenge groups.
Activation of lung macrophages and innate immune response genes was detected at
days 5 to 7 post-challenge. The kinetics of infection, both virological and
immunological, were broadly in line with human influenza A virus infections.
These more authentic infection models will be valuable in the determination of
anti-influenza efficacy of novel entities against less severe (and thus more
common) influenza infections.
|Administration, Inhalation
[MESH]
|Administration, Intranasal
[MESH]
|Aerosols/administration & dosage
[MESH]
|Animals
[MESH]
|Bronchoalveolar Lavage Fluid/cytology
[MESH]
|Computational Biology
[MESH]
|Disease Models, Animal
[MESH]
|Dogs
[MESH]
|Humans
[MESH]
|Influenza A Virus, H1N1 Subtype/*immunology
[MESH]