Susceptibility of the Aotus nancymaae owl monkey to eastern equine encephalitis.
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 10(4)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.
Espinosa
Benjamin J
BJ
Naval Medical Research Center Detachment-Lima, Peru. benjamin.espinosa@med.navy.mil
Weaver
Scott C
SC
Paessler
Slobodan
S
Brining
Douglas
D
Salazar
Milagros
M
Kochel
Tadeusz
T
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D016645:Aotidae / Q000276:immunology* / Q000821:virology*; D004195:Disease Models, Animal; D004663:Encephalitis Virus, Eastern Equine / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity*; D020242:Encephalomyelitis, Eastern Equine / Q000276:immunology* / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D006736:Horses; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010948:Viral Plaque Assay; D014766:Viremia / Q000821:virology
D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M