Evaluation of a ferret-specific formula for determining body surface area to improve chemotherapeutic dosing

OBJECTIVE To use CT-derived measurements to create a ferret-specific formula for body surface area (BSA) to improve chemotherapeutic dosing. ANIMALS 25 adult ferrets (19 live and 6 cadavers). PROCEDURES Live subjects were weighed, and body measurements were obtained by each of 3 observers while ferrets were awake and anesthetized. Computed tomography was performed, and a 3-D surface model was constructed with open-source imaging software, from which BSA was estimated. The CT-derived values were compared with BSA calculated on the basis of the traditional tape method for 6 cadavers. To further validate CT analysis software, 11 geometric shapes were scanned and their CT-derived values compared with those calculated directly via geometric formulas. Agreement between methods of surface area estimation was assessed with linear regression. Ferret-specific formulas for BSA were determined with nonlinear regression models. RESULTS Repeatability among the 3 observers was good for all measurements, but some measurements differed significantly between awake and anesthetized ferrets. Excellent agreement was found between measured versus CT-derived surface area of shapes, traditional tape- versus CT-derived BSA of ferret cadavers, and CT-derived BSA of cadavers with and without monitoring equipment. All surface area formulas performed relatively similarly. CONCLUSIONS AND CLINICAL RELEVANCE CT-derived BSA measurements of ferrets obtained via open-source imaging software were reliable. On the basis of study results, the recommended formula for BSA in ferrets would be 9.94 × (body weight)(2/3); however, this represented a relatively minor difference from the feline-derived formula currently used by most practitioners and would result in little practical change in drug doses

Immunogenicity and Efficacy of a Novel Multi-Antigenic Peptide Vaccine Based on Cross-Reactivity between Feline and Human Immunodeficiency Viruses

For the development of an effective HIV-1 vaccine, evolutionarily conserved epitopes between feline and human immunodeficiency viruses (FIV and HIV-1) were determined by analyzing overlapping peptides from retroviral genomes that induced both anti-FIV/HIV T cell-immunity in the peripheral blood mononuclear cells from the FIV-vaccinated cats and the HIV-infected humans. The conserved T-cell epitopes on p24 and reverse transcriptase were selected based on their robust FIV/HIV-specific CD8+ cytotoxic T lymphocyte (CTL), CD4+ CTL, and polyfunctional T-cell activities. Four such evolutionarily conserved epitopes were formulated into four multiple antigen peptides (MAPs), mixed with an adjuvant, to be tested as FIV vaccine in cats. The immunogenicity and protective efficacy were evaluated against a pathogenic FIV. More MAP/peptide-specific CD4+ than CD8+ T-cell responses were initially observed. By post-third vaccination, half of the MAP/peptide-specific CD8+ T-cell responses were higher or equivalent to those of CD4+ T-cell responses. Upon challenge, 15/19 (78.9%) vaccinated cats were protected, whereas 6/16 (37.5%) control cats remained uninfected, resulting in a protection rate of 66.3% preventable fraction (p = 0.0180). Thus, the selection method used to identify the protective FIV peptides should be useful in identifying protective HIV-1 peptides needed for a highly protective HIV-1 vaccine in humans

Both Feline Coronavirus Serotypes 1 and 2 Infected Domestic Cats Develop Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain: Its Implication to Pan-CoV Vaccine Development

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1 and FCoV2) demonstrated an amino acid sequence identity of 11.5% and a similarity of 31.8% with FCoV1 RBD (12.2% identity and 36.5% similarity for FCoV2 RBD). The sera from toms and queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins, but not with FCoV2 RBD. Thus, the queens and toms were infected with FCoV1. Additionally, the plasma from six FCoV2-inoculated cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. Hence, the sera from both FCoV1-infected cats and FCoV2-infected cats developed cross-reactive antibodies to SCoV2 RBD. Furthermore, eight group-housed laboratory cats had a range of serum cross-reactivity to SCoV2 RBD even 15 months later. Such cross-reactivity was also observed in FCoV1-positive group-housed pet cats. The SCoV2 RBD at a high non-toxic dose and FCoV2 RBD at a 60–400-fold lower dose blocked the in vitro FCoV2 infection, demonstrating their close structural conformations essential as vaccine immunogens. Remarkably, such cross-reactivity was also detected by the peripheral blood mononuclear cells of FCoV1-infected cats. The broad cross-reactivity between human and feline RBDs provides essential insights into developing a pan-CoV vaccine