Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants.

BACKGROUND AND AIMS: ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated G1P8 (KH0118) strain by Center for Research and Production of Vaccines and Biologicals (POLYVAC), Vietnam. This study compared the safety and immunogenicity of these two formulations. METHODS: A Phase 3, randomized, partially double-blinded, active-controlled study was conducted in healthy infants aged 60-91 days in Vietnam. Infants received two doses of ROTAVIN or ROTAVIN-M1 in a ratio of 2:1 with an interval of 8 weeks. Solicited reactions were collected for 7 days after each vaccination. Blood samples were collected pre-vaccination and 4 weeks after the second vaccination in a subset of infants. Non-inferiority criteria required that the lower bound of 95% confidence intervals (CIs) of the post-vaccination anti-rotavirus IgA GMC (Geometric Mean Concentration) ratio of ROTAVIN/ROTAVIN-M1 should be >0.5. A co-primary objective was to compare the safety of the two vaccines in terms of solicited reactions. RESULTS: A total of 825 infants were enrolled. The post-vaccination GMC was 48.25 (95% CI: 40.59, 57.37) in the ROTAVIN group and 35.04 (95% CI: 27.34, 44.91) in the ROTAVIN-M1 group with an IgA GMC ratio of 1.38 (95% CI: 1.02, 1.86) thus meeting the pre-set criteria for non-inferiority. A total of 605 solicited reactions were reported in 297 (36.0%) participants with 35.4% in the ROTAVIN group and 37.2% in the ROTAVIN-M1 group. There were no cases of intussusception or death reported in the study. CONCLUSIONS: Based on the data generated, it can be concluded that ROTAVIN is immunologically non-inferior and has similar safety profile to ROTAVIN-M1 when administered to infants in a two-dose schedule. Therefore, it can be considered as a more suitable option for programmatic use to prevent rotavirus diarrhoea in Vietnam and the Mekong region. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03703336, October 11, 2018.

Response of liver cells to insulin at 1 week postnatal as influenced by a prior action of the same hormone at the time of birth (hormonal imprinting): an electron microscopic study.

Liver cells of rats given a single insulin dose at birth (imprinted) do not alter from the controls at 1 week postnatal. When hormone treatment occurs at 1 week postnatal without any prior administration of it, an increase in glycogen and lipid with nuclear deposition of the latter can be seen. The cell surface displays a dense layer, and increased micropinocytosis is accompanied by an increase in the number of coated pits and vesicles. Liver cells of imprinted animals treated repeatedly at 1 week postnatal have much more glycogen and lipid, and more prominent endoplasmic reticulum but a less mature Golgi apparatus. The dense substance of the cell surface is missing and the signs of endocytosis are rarely seen. These alterations indicate the influence of imprinting on hormone binding and possibly on the next steps after interaction in the cell.

The effect of insulin on the liver cells of newborn rats. An electron microscopic study.

The liver of newborn rats contains neither glycogen nor lipid droplets. These latter, sometimes in fusion, still could be found in the cytoplasm and the nucleus as well, following a five-minute action of insulin at a dose of 0.2 IU/animal. The lipid droplets were in close relationship with the mitochondria. This time the glycogen, either in fields or rosettes, was missing. Thirty minutes after treatment the fields of glycogen could be well seen. The experiments demonstrated an exclusive sequence of events starting with the receptor and its signal insulin on neonatal liver cells and resulting in a morphological picture (involving first lipid droplets, then glycogen), similar to that of the adult liver cells.

Response to thyroid stimulating hormone in 1-week-old rat thyroid gland after pretreatment with the same hormone in newborn conditions (hormonal imprinting).

Compared with control animals without hormone action, newborn rats treated with thyroid stimulating hormone (TSH) developed more exocytotic vesicles and enlarged endoplasmic reticulum filled with products in the thyroid gland up to the first postnatal week. A single administration of the hormone in newborn rats (imprinting) resulted in a long-lasting effect on the functioning of the cells of the thyroid gland. Single hormone action in postnatal 1-week-old animals provoked the discharge of products from the cells into the follicles of the thyroid gland with a concurrent endocytosis within 5 min after treatment. A similar but more vigorous effect was demonstrable in animals treated with TSH in newborn (hormonal imprinting) and postnatal 1-week-old conditions. Such events were accompanied by the death of certain cells while others developed myelin-like structures and showed signs of folliculogenesis in the cytoplasm.

The effect of thyrotropic hormone (TSH) on the thyroid gland of the newborn rat. An electron microscopic study.

The activity of the thyroid gland of the newborn rat is influenced by the treatment of TSH. Shortly after hormone injection, its effects can be detected in the synthesis and storage of the colloid. In a longer term (30 min and 60 min) the morphological signs of resorption and secretion are evident. At this early age the cellular compartments involved in the secretory pathway of the cells are still not complete in maturation (less developed Golgi complex, missing secretory vesicles and micropinocytotic vesicles). According to our results, even TSH administration cannot influence this picture in the short term. Our work supports the intracellular way of folliculogenesis, and the TSH action as a promoter in this way.