IMPORTANCE A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. OBJECTIVE To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. INTERVENTIONS In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). DESIGN, SETTING, AND PARTICIPANTS Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. MAIN OUTCOMES AND MEASURES The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. CONCLUSIONS AND RELEVANCE In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials.

No abstract

Background: Older people (≥60 years old) are particularly vulnerable to influenza virus infection, and vaccine is effective in reducing the disease burden in this population. However, it remains obscure whether their antibody response is lower than those of younger adults (18-60 years old). Thus, this meta-analysis was performed to compare the immunogenicity of influenza vaccines and understand their association with real-world vaccine effectiveness (VE) between these two age groups. Methods: A systematic literature search was conducted to identify relevant studies from Jan 01, 2008 to Nov 10, 2018. These are randomized controlled trials that included older adult samples, which assessed the immunogenicity of inactivated quadrivalent influenza vaccines produced in embryonated eggs. We excluded the studies focused only in children or adults. The outcomes were seroprotecton rate (SPR) and seroconversion rate (SCR). Results: Six studies were eventually included in the present meta-analysis (7,976 participants). For the SPR, the pooled risk ratio (RR) was 0.92 (95% CI: 0.90-0.94, I 2 = 66%, P < .0001) for A/H1N1 and 0.94 (95% CI: 0.90-0.98, I 2 = 91%, P = .002) for B/Victoria, and the antibody responses of A/H3N2 and B/Yamagata were similar in the two age groups. For the SCR, the pooled RR was 0.85 (95% CI: 0.76-0.94, I 2 = 93%, P = .003), 0.77 (95% CI: 0.66-0.91, I 2 = 94%, P = .002), and 0.83 (95% CI: 0.71-0.96, I 2 = 94%, P = .02) for A/ H1N1, B/Victoria and B/Yamagata, respectively, and the antibody responses of A/H3N2 were similar in the two groups. Some variations were found in the antibody responses across virus types and subtypes after influenza vaccination. Conclusion:The SPR and SCR of older adults were lower than those in younger adults for A/H1N1 and B/Victoria, while the two age groups had similar antibody responses for A/H3N2. The antibody responses to vaccines were not significantly associated with real-world VE, indicating that antibody response might not fully reflect the vaccine effectiveness of A/H3N2.

Naringenin (NRG) is a natural flavonoid compound abundantly present in citrus fruits and has the potential to treat respiratory disorders. However, the clinical therapeutic effect of NRG is limited by its low bioavailability due to poor solubility. To enhance the solubility, naringenin nanosuspensions (NRG-NSps) were prepared by applying tocopherol polyethylene glycol succinate (TPGS) as the nanocarrier via the media-milling method. The particle size, morphology, and drug-loading content of NRG-NSps were examined, and the stability was evaluated by detecting particle size changes in different physiological media. NRG-NSps exhibited a flaky appearance with a mean diameter of 216.9 nm, and the drug-loading content was 66.7%. NRG-NSps exhibited good storage stability and media stability. NRG-NSps presented a sustainable release profile, and the cumulative drug-release rate approached approximately 95% within 7 d. NRG-NSps improved the antitussive effect significantly compared with the original NRG, the cough frequency was decreased from 22 to 15 times, and the cough incubation period was prolonged from 85.3 to 121.6 s. Besides, NRG-NSps also enhanced expectorant effects significantly, and phenol red secretion was increased from 1.02 to 1.45 μg/mL. These results indicate that NRG-NSps could enhance the bioavailability of NRG significantly and possess a potential clinical application.