RESUMO
BackgroundProtection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. MethodsThis phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50{micro}g dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID50) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. ResultsFrom March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). ConclusionsHigher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. Clinicaltrials.govNCT05289037
RESUMO
Genitourinary syndrome of menopause significantly affects the quality of life in postmenopausal women with few evidence-based alternatives to vaginal estrogen for women with contraindications. This systematic review evaluates the evidence for vaginal vitamin E efficacy in reducing patient-reported genitourinary symptoms in healthy postmenopausal women compared to placebo or vaginal control therapy. This systematic review evaluated randomized controlled trials before October 2020 that assessed the efficacy of vitamin E vaginal suppositories in reducing genitourinary symptoms in postmenopausal women compared with a control group of healthy postmenopausal women. Outcomes included patient-perceived genitourinary symptoms. Of the 31 studies, four met the inclusion criteria. One 8-week trial (n = 42) found a significant reduction in vaginal symptoms in the 1 mg vitamin E group than the placebo group (difference in means, 5.3; 95% confidence interval [CI], 4.4 to 6.2). Another 8-week trial (n = 40) found 5 mg vaginal hyaluronic acid superior to 1 mg vitamin E (difference in means –0.50, 95% CI, –0.95 to –0.05). Two 12-week trials (n = 52 in each) found no difference between 0.5 g vaginal estrogen and 100 IU vaginal vitamin E in healthy postmenopausal women (difference in means: –0.19, 95% CI, –4.4 to 4.0, and −3.47, 95% CI, −13.8 to 6.8). Evidence from small, limited studies suggests that vaginal vitamin E may be effective in alleviating symptoms of genitourinary syndrome of menopause; however, additional high-quality studies are needed to determine efficacy, ideal dosing, and long-term safety.
