A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20-45 years: A randomized, blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial.

BACKGROUND: Human papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent). METHODS: 1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20-26, 27-35, or 36-45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > -10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5. RESULTS: Among the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded -10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths. CONCLUSIONS: This study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.

Effects of dietary threonine on growth and immune response of oriental river prawn (Macrobrachium nipponense).

A 70-day feeding trial was conducted to ascertain the effects of threonine on immune response of juvenile oriental river prawn (Macrobrachium nipponense). Six isonitrogen and isolipidic feeds were formulated according to levels of dietary threonine (0.35%, 0.79%, 1.18%, 1.67%, 2.08% and 2.48% respectively). The juvenile prawns were divided into six groups with four replicates, and stocked into 24 tanks with 50 prawns per tank (initial weight 0.20 ± 0.02 g). The results showed a significant increasing trend of final body weight, specific growth rate, protein efficiency ratio, and weight gain rate when threonine levels increased to 1.67% (P < 0.05). However, feed intake, feed conversion ratio, and whole-body lipid composition significantly decreased as threonine levels in the feed increased up to 1.67% (P < 0.05). Moreover, haemolymph N-urea content was significantly lowest at 1.67% threonine level (P < 0.05), whereas glucose was highest at 0.79% followed by 1.67% of threonine levels in the feeds. Aspartate aminotransferase (AST) enzyme activities were significantly decreased by an imbalance (except 1.67%) of threonine in the feed (P < 0.05). Activities of Alanine aminotransferase (ALT) and albumen (ALB) were not significantly affected by threonine in the feed (P > 0.05). Excessive dietary threonine level (2.48%) significantly activated haemolymph catalase (CAT) activity (P < 0.05), whereas malondialdehyde (MDA) content was significantly affected by deficient (0.35% and 0.79%) dietary threonine levels (P < 0.05). Inducible nitric oxide synthase (iNOS) activity and haemolymph complement component 4 (C4) content were significantly decreased by deficient levels of threonine in the feed (P < 0.05). Excess threonine concentration significantly down-regulated Toll, Dorsal, Relish, and heat shock protein 60 (Hsp60) gene expressions in the hepatopancreas of M. nipponense (P < 0.05), while all genes were significantly up-regulated by the optimal (1.67%) threonine level (P < 0.05). The threonine level at which maximum specific growth rate of M. nipponense occurred was estimated by second degree polynomial regression analysis as 1.65% of threonine level, equivalent to 4.44% dry weight bases of protein in the feed.

Molecular cloning and characterization of an estrogen receptor gene in the marine polychaete Perinereis aibuhitensis.

Estrogen receptors (ERs) are the primary mediators of estrogen signaling, and play crucial roles in the reproduction and development of vertebrates. The full-length cDNA of Perinereis aibuhitensis estrogen receptor (paER) was cloned and characterized for the first time. The positions of the cysteine residues and the residues around them, which constitute two zinc finger motifs and a P-box, are conserved in both vertebrates and invertebrates. A phylogenetic analysis revealed that paER is an orthologue of ER in the polychaete Platynereis dumerilii. A tissue distribution analysis of paER mRNA showed that it is expressed in various tissues, including the body wall, head, esophageal gland, esophagus, stomach, and most strongly in the intestines. Its expression was also measured in P. aibuhitensis after exposure to 17ß-estradiol (E2) for 48h. The paER mRNA levels in the body wall were measured after 6, 12, 24, and 48h in E2-exposed and control animals. However, no significant differences in paER expression were observed between them at any time point. This report describes the first molecular characterization of full-length paER and its tissue-specific expression in P. aibuhitensis.