Product review of the rotavirus vaccines ROTASIIL, ROTAVAC, and Rotavin-M1.

Rotavirus is the leading cause of severe dehydrating gastroenteritis and death due to diarrhea among children under 5, causing over 180,000 under-5 deaths annually. Safe, effective rotavirus vaccines have been available for over a decade and are used in over 98 countries. In addition to the globally available, WHO-prequalified ROTARIX (GSK) and RotaTeq (Merck), several new rotavirus vaccines have attained national licensure - ROTAVAC (Bharat Biotech) and ROTASIIL (Serum Institute of India), licensed and manufactured in India and now WHO-prequalified, and Rotavin-M1 (PolyVac), licensed and manufactured in Vietnam. In this review, we summarize the available clinical trial and post-introduction evidence for these three new orally administered rotavirus vaccines. All three vaccines have demonstrated safety and efficacy against rotavirus diarrhea, although publicly available preclinical data are limited in some cases. This expanding product landscape presents a range of options to optimize immunization programs, and new presentations of each vaccine are currently under development.

Higher anhedonia during withdrawal from initial opioid exposure is protective against subsequent opioid self-administration in rats.

RATIONALE: Understanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute effects of initial drug exposure predicts later addiction vulnerability in both humans and animals, but the relationship between sensitivity to withdrawal from initial drug exposure and later drug use vulnerability is unclear. OBJECTIVE: The goal of the current study was to evaluate whether the degree of anhedonia experienced during withdrawal from early opioid exposure predicts subsequent vulnerability to opioid self-administration. METHODS: Rats were first tested for withdrawal sensitivity following acute injections of morphine (i.e., "acute dependence"), measured as elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during naloxone-precipitated and spontaneous withdrawal. Rats were then tested for addiction-like behavior using various measures of i.v. morphine self-administration (MSA) including acquisition, demand, extinction, and reinstatement induced by morphine, stress, and/or drug-associated cues. RESULTS: Greater naloxone-precipitated withdrawal across repeated morphine injections and greater peak spontaneous withdrawal severity following a single morphine injection were associated with lower addiction-like behavior on multiple MSA measures. Withdrawal-induced anhedonia predicted a wider range of MSA measures than did any individual measure of MSA itself. CONCLUSIONS: Our data establish WIA as one of the first behavioral measures to predict individual differences in opioid SA in rodents. This model promises to be useful for furthering our understanding of behavioral and neurobiological mechanisms underlying vulnerability to opioid addiction.