Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection. Nebulized human mAbs are detectable in nasal, oropharyngeal, and bronchoalveolar lavage (BAL) samples. SARS-CoV-2 mAb treatment significantly reduces levels of SARS-CoV-2 viral RNA and infectious virus in the upper and lower respiratory tracts relative to controls. Reductions in lung and BAL virus levels correspond to reduced BAL inflammatory cytokines and lung pathology. Aerosolized antibody therapy for SARS-CoV-2 could be effective for reducing viral burden and limiting disease severity.

Obtaining quality oocytes is a prerequisite for ART-based studies. Here we describe a method for transabdominal ultrasound-guided (US) oocyte retrieval in rhesus macaques (Macaca mullata) and compare it to the standard surgical approach using laparoscopy (LAP). We analyzed oocyte yield from six continuous reproductive seasons (2017–2023) that included n = 177 US-guided and n = 136 laparoscopic oocyte retrievals. While the ultrasound-guided technique retrieved significantly fewer oocytes on average (LAP: 40 ± 2 vs. US: 27 ± 1), there was no difference in the number of mature metaphase II oocytes (MII) between the two techniques (LAP: 17 ± 1 vs. US: 15 ± 1). We show that oocytes retrieved by the ultrasound-guided approach fertilize at the same rates as those obtained via the laparoscopic procedure (LAP Fert Rate: 84% ± 2% vs. US Fert Rate: 83% ± 2%). In conclusion, minimally invasive ultrasound-guided oocyte retrieval improves animal welfare while delivering equivalent numbers of mature oocytes, which are ideal for ART. Furthermore, we show that oocyte competency, as represented by fertilization rate, is not affected by retrieval technique. Therefore, the Oregon National Primate Research Center (ONPRC) has adopted the ultrasound-guided approach as the standard technique for oocyte retrieval.

The rhesus macaque (Macaca mulatta) is a valuable model for pregnancy research due to its physiological similarity to humans and the ability to conduct studies in a controlled environment. Our previous work used non-invasive imaging methods to assess placental hemodynamics across gestation with correlative tissue analysis post-delivery. Here, we expand access to longitudinal timepoints from ongoing pregnancies by obtaining placental biopsies using ultrasound-guided needle aspiration. This approach aligns with New Approach Methods (NAMs) and supports animal welfare by reducing the number of animals required. We describe a chorionic villus sampling (CVS) simulation model which facilitates training to gain proficiency in technical skills prior to performing the procedure on animals. We report outcomes from three rhesus macaques that underwent CVS three times between gestational days 40 to 106 (term: 165 days). Although biopsy samples are smaller than whole placenta, tissue yields were sufficient for multiple uses. We demonstrate (1) appropriate histology from aspirated samples, (2) good RNA quality and yield, and (3) the ability to isolate trophoblast organoids, an advancement in NAMs that reduces the need for first-trimester surgical delivery. No spontaneous preterm delivery occurred following serial CVS procedures, supporting the use of this sampling method to maximize animal utilization in longitudinal pregnancy studies.

The rhesus macaque (Macaca mulatta) is a valuable model for pregnancy research due to its physiological similarity to humans and the ability to conduct studies in a controlled environment. Our previous work used noninvasive imaging methods to assess placental hemodynamics across gestation with correlative tissue analysis post-delivery. Here, we expand access to longitudinal timepoints from ongoing pregnancies by obtaining placental biopsies using ultrasound-guided needle aspiration. This approach aligns with New Approach Methods (NAMs) and supports animal welfare by reducing the number of animals required. We describe a chorionic villus sampling (CVS) simulation model which facilitates training to gain proficiency in technical skills prior to performing the procedure in animals. We report outcomes from three rhesus macaques that underwent CVS three times between gestational days 40 to 106 (term: 165 days). Although biopsy samples are smaller than whole placenta, tissue yields were sufficient for multiple uses. We demonstrate 1) appropriate histology from aspirated samples, 2) good RNA quality and yield, and 3) the ability to isolate trophoblast organoids, a NAMs advancement that reduces the need for first-trimester surgical delivery. No adverse outcomes occurred following serial CVS procedures, supporting the use of this sampling to maximize animal utilization in longitudinal pregnancy studies.