TY - JOUR
T1 - Susceptibility of the Aotus nancymaae owl monkey to eastern equine encephalitis
AU - Espinosa, Benjamin J.
AU - Weaver, Scott C.
AU - Paessler, Slobodan
AU - Brining, Douglas
AU - Salazar, Milagros
AU - Kochel, Tadeusz
N1 - Funding Information:
The views, opinions, and findings contained in this report are those of the authors and do not reflect official policy or positions of the Department of the Navy, Department of Defense, or the United States Government. We are military service members. This work was prepared as part of our official duties. Title 17 USC § 105 provides that “Copyright protection under this title is not available for any work of the United States Government” Title 17 USC § 101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties. This work was supported by a grant from NIAID through the Western Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, NIH grant number U54 AI057156.
PY - 2009/3/10
Y1 - 2009/3/10
N2 - Eastern equine encephalitis virus (EEEV) is an arthropod-borne virus associated with life-threatening encephalitis in humans, equines, birds and many other domestic animals. To investigate the suitability of the Aotus nancymaae New World owl monkey as a viable animal model for EEE candidate vaccine testing we used clinical presentation, serology, viral isolation and PCR to evaluate pathogenesis and immunity in infected animals. Monkeys were inoculated subcutaneously (SQ) or intranasally (IN) with 104 pfu of virulent EEEV and were initially followed for 45 days. While none of the animals displayed clinical signs of disease, all of the SC inoculated animals (n = 6) manifested a viremia averaging 3.2 days (±0.8 days). Likewise, serologic responses (IgM, IgG and PRNT) were observed in all SC infected animals. Interestingly, none of the IN inoculated animals (n = 6) became viremic or mounted an antibody response and no pathological abnormalities were observed in two animals that were necropsied on day 6 post-infection (p.i.) from each group. To determine if the antibodies produced by the SC inoculated animals were protective against homologous challenge, three animals from the SC group were serologically evaluated on day 253 p.i. and were administered an inoculum identical to initial challenge on day 270 p.i. A positive control group of four naïve animals was also infected as before. All of the naïve positive control animals manifested a similar viremia as observed initially, averaging 2.75 days (±0.5 days) while none of the previously challenged animals became viremic. On days 45 and 253 p.i. geometric mean PRNT titers in the SC group were 453 and 101, respectively. This study demonstrates that the Aotus nancymaae can be reproducibly infected with EEE virus and can serve as a suitable model for infection and immunogenicity for the evaluation of candidate vaccines against EEEV.
AB - Eastern equine encephalitis virus (EEEV) is an arthropod-borne virus associated with life-threatening encephalitis in humans, equines, birds and many other domestic animals. To investigate the suitability of the Aotus nancymaae New World owl monkey as a viable animal model for EEE candidate vaccine testing we used clinical presentation, serology, viral isolation and PCR to evaluate pathogenesis and immunity in infected animals. Monkeys were inoculated subcutaneously (SQ) or intranasally (IN) with 104 pfu of virulent EEEV and were initially followed for 45 days. While none of the animals displayed clinical signs of disease, all of the SC inoculated animals (n = 6) manifested a viremia averaging 3.2 days (±0.8 days). Likewise, serologic responses (IgM, IgG and PRNT) were observed in all SC infected animals. Interestingly, none of the IN inoculated animals (n = 6) became viremic or mounted an antibody response and no pathological abnormalities were observed in two animals that were necropsied on day 6 post-infection (p.i.) from each group. To determine if the antibodies produced by the SC inoculated animals were protective against homologous challenge, three animals from the SC group were serologically evaluated on day 253 p.i. and were administered an inoculum identical to initial challenge on day 270 p.i. A positive control group of four naïve animals was also infected as before. All of the naïve positive control animals manifested a similar viremia as observed initially, averaging 2.75 days (±0.5 days) while none of the previously challenged animals became viremic. On days 45 and 253 p.i. geometric mean PRNT titers in the SC group were 453 and 101, respectively. This study demonstrates that the Aotus nancymaae can be reproducibly infected with EEE virus and can serve as a suitable model for infection and immunogenicity for the evaluation of candidate vaccines against EEEV.
KW - Animal model
KW - Aotus nancymaae
KW - Eastern equine encephalitis (EEE)
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U2 - 10.1016/j.vaccine.2009.01.029
DO - 10.1016/j.vaccine.2009.01.029
M3 - Article
C2 - 19186197
AN - SCOPUS:60849105343
SN - 0264-410X
VL - 27
SP - 1729
EP - 1734
JO - Vaccine
JF - Vaccine
IS - 11
ER -