Pre-Hospital Administration of Remdesivir During a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Outbreak in a Skilled Nursing Facility.

Completion of a 5-day course of remdesivir was associated with approximately 17-fold increased odds of survival among a sample of 54 nursing home residents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the course of an outbreak from October to December 2020. Remdesivir was well tolerated; administration was logistically feasible in a pre-hospital environment.

Investigating the Effect of Enterally Administered Capromorelin on Body Weight in Mice (Mus musculus).

Significant weight loss in mice (Mus musculus) is a welfare concern and can alter physiology and behavior in ways that may confound research aims. In this study, factorial design was used to investigate the effect of enterally administered capromorelin on changes in mouse body weight overall and with various research-related interventions, such as administration of analgesics, anesthesia, or surgery. BALB/c mice (n = 61 [27 males/34 females] for analysis) were randomized into 8 intervention-treatment groups with 2 treatment allocations: capromorelin (10 mg/kg) or control, and 4 intervention allocations: no intervention; buprenorphine extended-release (XR) alone; buprenorphine XR, meloxicam, and anesthesia; or surgery under anesthesia with buprenorphine XR, meloxicam, and bupivacaine administered. Mice were habituated to handling, weighing, and voluntary consumption of condensed milk, which was used as the control solution and later a vehicle for capromorelin delivery, for 5 d (days 0 to 4). Then, mice received their interventions followed by 3 days of daily treatment or control administration (days 7 to 9). Body weights were measured daily (days 8 to 11 and day 14) to compare with baseline weights (days 0 to 4 and day 7) and evaluate for treatment and intervention effects on body weight. The interventions resulted in a decrease in group body weights 3 and 4 d after the interventions were conducted. Overall, body weights increased more in mice given capromorelin compared with control, and mice treated with capromorelin returned to, or exceeded, baseline weights faster. The weight loss was mitigated by capromorelin administration in all interventions except for the buprenorphine XR-only group. It is recommended to clinically consider enterally administered capromorelin to mitigate research-induced weight loss in mice.

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Field evaluation of a lethal ovitrap for the control of Aedes aegypti (Diptera: Culicidae) in Thailand.

In 1999 and 2000 we evaluated a lethal ovitrap (LO) for the control of Aedes aegypti (L.) in three villages in Ratchaburi Province, Thailand. Two blocks of 50 houses (a minimum of 250 m apart) served as treatment and control sites in each village, with each house in the treatment area receiving 10 LOs. Thirty houses in the center of each treatment and control block were selected as sampling sites, with larval and adult mosquito sampling initiated when LOs were placed. Sampling was conducted weekly in 10 of the 30 houses at each site, with each block of 10 houses sampled every third week. Sampling continued for 30 wk. Efficacy of the LO was evaluated by determining number of containers with larvae and/or pupae per house and number of adult mosquitoes collected inside each house. In 1999, the LO had a negligible impact on all measures of Ae. aegypti abundance that were assessed; however, fungal contamination of insecticide-impregnated strips may have been responsible for the low efficacy. In 2000, significant suppression was achieved based on changes in multiple entomologic criteria (containers with larvae, containers with pupae, and number of adult Ae. aegypti); however, control was not absolute and neither immature nor adult Ae. aegypti were ever eliminated completely. We conclude that the LO can reduce adult Ae. aegypti populations in Thailand; however, efficacy of the LO is lower than desired due primarily to the high number of alternative oviposition sites. LO efficacy may be improved when used as part of an integrated control program that places emphasis on reduction of adjacent larval habitats. Further studies are required to assess this issue.