Comparative pharmacokinetics of porcine and human anti-influenza hemagglutinin monoclonal antibodies in outbred pigs and minipigs

Abstract

Assessing the pharmacokinetics of monoclonal antibodies (mAbs) in relevant animal models is essential for designing improved formulations and developing mAb delivery platforms. We have established the pig, a large natural host animal for influenza with many similarities to humans, as a robust model for testing the therapeutic efficacy of anti-influenza mAbs and evaluating mAb delivery platforms. Here, we compared the pharmacokinetic characteristics of two anti-influenza hemagglutinin mAbs, human 2-12C and porcine pb27, in Göttingen minipigs and Landrace × Large White outbred pigs. Minipigs offer the advantage of a more stable weight, whereas outbred pigs are more readily available but exhibit rapid growth. Outbred pigs and minipigs showed similar pharmacokinetics and a similar porcine pb27 half-life (half-life of 15.7 days for outbred pigs and 16.6 days for minipigs). In contrast, the half-life of human 2-12C was more rapid in two of the minipigs but not in the outbred pigs, correlating with the development of antidrug antibodies in the two minipigs. Our results demonstrate that both outbred pigs and minipigs are appropriate models for pharmacokinetic studies and the evaluation of mAb delivery platforms, potentially bridging the gap between small animals and human trials.

Keywords: 2-12C; anti-influenza monoclonal antibodies; minipigs; outbred pigs; pb27; pharmacokinetic.

Figure 1

Experimental design. Recombinant 2-12C or pb27 at 3.5 mg/kg were administered intravenously to four minipigs or four outbred pigs. Clotted blood was obtained at the indicated times.

Figure 2

PK of 2-12C in outbred and minipigs. Overall representation of weight and 2-1C concentration in outbred and minipigs (A). 2-12C serum ELISA titers in individual minipigs (B) and outbred pigs (C). Neutralizing titers in the serum of 2-12C treated pigs. Fifty percent inhibition titers of individual minipigs (D) and outbred pigs (E) over the time course. ADA responses in both outbred and minipigs (F).

Figure 3

PK of pb27 in outbred and minipigs. Overall representation of weight and pb27 concentration in outbred and minipigs (A). pb27 serum ELISA titers in individual minipigs (B) and outbred pigs (C). Neutralizing activity in the serum of pb27-treated pigs. Fifty percent inhibition titers of individual minipigs (D) and outbred pigs (E) over the time course.