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We assessed the safety, immunogenicity and antibody persistence of two- and three-dose schedules of the novel bivalent HPV16/18 vaccine (HPV-2, Walrinvax) in the per-protocol target population of initially seronegative 9–14 year-old girls, including a non-inferiority comparison with the three-dose schedule in 18–26 year-old women. This randomized phase 3b trial in Guangxi Zhuang Autonomous Region, China, involved healthy Chinese females in two age cohorts; 600 girls aged 9–14 years and 300 women aged 18–26 years. Girls were randomly assigned (1:1) to receive either two (Months 0,6) or three (Months 0,2,6) intramuscular doses of HPV-2. All participants were monitored for immunogenicity as neutralizing antibodies up to 36 months. Primary objectives were non-inferiority analyses of immunogenicity between two- and three-dose girl groups and adult women at Month 7; safety assessments were based on participant-completed diary cards. All groups demonstrated marked increases in neutralizing antibodies against HPV 16 and 18 that persisted above baseline to 36 months. Month 7 responses in both girl groups were non-inferior to those in the women and were statistically higher after two-doses than girls or women who received three doses. GMTs waned after month 7, but then maintained a plateau level until month 36. Vaccination was well tolerated in all groups with no serious adverse events reported. Immune responses to two doses of HPV-2 vaccine in adolescent girls were non-inferior to those after three doses in young women, an age cohort in which clinical efficacy of HPV-2 against cervical cancer has been demonstrated. [ABSTRACT FROM AUTHOR]

• Low or high doses of VLP HPV vaccine were well tolerated in 9–45 year-old females. • Three HPV vaccinations elicited protective immune responses in 100% of vaccinees. • HPV vaccination did not result in any severe or serious adverse event. • Reactogenicity and immunogenicity were not affected by increasing dosage of HPV vaccine. We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9–45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMT HPV 16 = 10816 [95 % CI: 7824–14953]), GMT HPV 18 = 3966 [95 % CI: 2693–5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848–19333], GMT HPV 18 = 3428 [95 % CI: 2533–4639]). The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9–45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study. [ABSTRACT FROM AUTHOR]

• Reports of Mycobacterium colombiense infection are extremely rare and are often overlooked. • We first report the clinical features of disseminated M. colombiense infection. • Patients infected with M. colombiense can present as disseminated infections. • Metagenomic next-generation sequencing plays a crucial role in early diagnosis of M. colombiense infection. • Early antinontuberculous combination therapy improves the clinical prognosis. Localized or disseminated infection caused by different nontuberculous mycobacteria (NTM) species has been increasingly reported in recent years, but reports of Mycobacterium colombiense infection are extremely rare. Herein, we analyzed the clinical features of patients with disseminated M. colombiense infection. Patients diagnosed with disseminated M. colombiense infection between February 4, 2016 and August 25, 2021 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed. NTM infection was diagnosed in 248 HIV-negative patients. Of these, nine patients with disseminated M. colombiense infection were enrolled. Five of these patients were positive for anti-interferon-γ autoantibodies. The lung, lymph nodes, bones, and joints were the most commonly involved organs. Anemia, fever, lymphadenopathy, cough and expectoration, and ostealgia were the most common symptoms. The levels of white blood cells and neutrophils were increased in eight patients. M. colombiense was detected by both metagenomic next-generation sequencing (mNGS) and culture in four patients and only by mNGS in the remaining five patients. All patients received combination anti-NTM therapy; five underwent surgery. The condition of eight patients improved, and one died during the treatment. Patients infected with M. colombiense can present as disseminated infections, easily involving multiple organs, such as the lung, lymph nodes, bone, and joints, with fever, lymphadenopathy, and increased white blood cell and neutrophil counts. mNGS plays a crucial role in the early diagnosis of M. colombiense infection. Once diagnosed, timely and effective anti-NTM therapy, combined with local surgery if necessary, can improve the prognosis of patients with this condition. [ABSTRACT FROM AUTHOR]

• Rs2295080 polymorphism of MTOR gene may be associated with MPA susceptibility in a Guangxi population of China and G allele might be an important protective factor. • The haplotype AAT was correlated with increasing susceptibility of MPA. • The six-locus model was identified as the best interaction model. Microscopic polyangiitis (MPA) onset is affected by genetic predisposition. Autophagy plays a certain role in antineutrophil cytoplasmic antibody-associated vasculitis developing. A key factor in autophagy regulating, the genetic polymorphism of MTOR gene is essential. The objective was to explore the associations between MTOR gene polymorphism and MPA susceptibility in a Guangxi population of China. A sum of 208 MPA cases and 209 healthy volunteers from Guangxi in this case-control study, four important single nucleotide polymorphism (SNP) loci of MTOR gene including rs3806317, rs1064261, rs1883965 and rs2295080 were examined. Multiplex polymerase chain reaction combined with high-throughput sequencing was performed. Subgroup analysis was evaluated by gender and ethnicity. Linkage disequilibrium and haplotype analysis were tested. Multi-SNPs interaction among mTOR signaling pathway was assessed. For rs2295080, homozygous mutant GG genotype was associated with a decreased susceptibility of MPA in recessive model (OR = 0.38, 95%CI: 0.14–1.00, p = 0.040), particularly in the subgroup of female (OR = 0.16, 95%CI: 0.03–0.74, p = 0.006) and Han population (OR = 0.32, 95%CI: 0.10–1.00, p = 0.034). Individual carrying G allele was linked with decreasing MPA susceptibility in Han population of Guangxi (OR = 0.65, 95%CI: 0.44–0.97, p = 0.036). In haplotype analysis, the haplotype AAT was correlated with increasing susceptibility of MPA (OR = 1.347, 95%CI: 1.004–1.807, p = 0.046). Moreover, in the multi-SNPs interaction analysis, the six-locus model was identified as the best interaction model (p < 0.05). These findings suggest that rs2295080 polymorphism of MTOR gene may be associated with MPA susceptibility in a Guangxi population of China and G allele might be an important protective factor. [ABSTRACT FROM AUTHOR]