Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an appropriate dose of the candidate vaccine for an efficacy study. METHODS: This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389. FINDINGS: 603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented. INTERPRETATION: The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation. FUNDING: National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.

[Impacts of antiretroviral treatment on drug use and high risk sexual behaviors among HIV-positive MMT clients].

OBJECTIVE: To explore the impacts of antiretroviral treatment on drug use and high risk sexual behaviors among HIV-positive MMT clients. METHODS: A cross-sectional study was conducted in patients undergoing ART (ART-experienced) and patients not undergoing ART (ART-naive) attending MMT in 5 clinics in Yunnan Honghe and Dehong prefectures in 2014. A questionnaire was designed to collect socio-demographic characteristics, ART and MMT information and sexual and drug use behaviors within 3 months before the investigation was conducted. Logistic regression analysis was conducted to identify the predictors for drug use and risky sexual behaviors. RESULTS: A total of 328 cases were included in the analysis, among which 202 were ART-experienced and 126 were ART-naÏve. Among 152 respondents who were sexually active, 61 (40.1%) reported having unprotected sex (UPS) with their regular partners in the prior 3 months. A total of 57.6% (189/328) of the respondents used drugs in the prior 3 months. Multiple logistic regression analysis revealed that younger than 35 years old (OR = 3.57, 95% CI: 1.23-10.37), fertility desire (OR = 4.47, 95% CI: 1.49-13.41), partner being HIV-positive (OR = 4.62, 95% CI: 1.80-11.86), length of MMT attendance less than 5 years (OR = 2.92, 95% CI: 1.14-7.53), agreed that it was necessary to use condom no matter the viral load is high or low (OR = 0.14, 95% CI: 0.04-0.51) were protective factors of UPS in the prior 3 months. Multiple logistic regression analysis revealed that being Han (OR = 0.46, 95% CI: 0.24-0.89), feeling having good health status (OR = 0.39, 95% CI: 0.18-0.85), being enrolled in ART (OR = 0.32, 95% CI: 0.17-0.60) were protective factors for drug use in the prior three months, having contact with drug using friends (OR = 4.41, 95% CI: 2.31-8.29), having experience of missing an MMT dose (OR = 3.47, 95% CI: 1.92-6.29), and not satisfied with current MMT dose (OR = 13.92, 95% CI: 3.24-59.93) were risk factors for drug use during the prior three months. CONCLUSION: ART was not associated with risky sexual behavior and drug use in the prior 3 months in this population. Future interventions should promote ART among this population, and provide education at the same time to prevent the emergence of cross infections and drug-resistant strains.

Immunogenicity and safety of an enterovirus 71 vaccine in children aged 36-71 months: A double-blind, randomised, similar vaccine-controlled, non-inferiority phase III trial.

Background: The enterovirus 71 (EV71) vaccine produced by Wuhan Institute of Biological Products Co., Ltd. (WIBP) (B-EV71) has been given to children aged 6-35 months, and it has shown good safety, immunogenicity and efficacy. However, the administration of EV71 vaccine in children aged 36-71 months, which is another target population, needs further exploration. Methods: We conducted a double-blind, randomised, controlled, non-inferiority phase III clinical trial in children aged 36-71 months, with a further comparison group of children aged 6-35 months in China. Children aged 6-71 months with no history of hand, foot and mouth disease or prior-vaccination of EV71 vaccine were eligible and recruited. Eligible participants aged 36-71 months were randomly assigned (1:1) to receive two doses of the B-EV71 vaccine (Older-B group) or the control EV71 vaccine (C-EV71 vaccine, produced by Institute of Medical Biology, Chinese Academy of Medical Sciences) (Older-C group), administered at a 30-day interval. Eligible participants aged 6-35 months were enrolled consecutively to receive two doses of the B-EV71 vaccine (Younger-B group) at a 30-day interval. Participants, investigators and those assessing outcomes were masked to the vaccine received. Non-inferiority analyses were conducted to compare the immunogenicity of EV71 vaccine in the Older-B group with that in the Older-C and Younger-B groups. Non-inferiority margins were 10% for seroconversion rate differences and 0.5 for geometric mean titre (GMT) ratios. The primary endpoints were the GMT level and seroconversion rate of anti-EV71 neutralising antibody 30 days after the second dose of vaccination. The primary analysis was performed in the per-protocol population. Safety analyses were conducted amongst participants receiving at least one dose of vaccine. This trial was registered at Chinadrugtrials.org.cn (#CTR20192345). Findings: Between June 3 and June 30, 2020, 1600 participants were enrolled and assigned, including 625 participants in the Older-B group, 625 participants in the Older-C group and 350 participants in the Younger-B group. The seroconversion rate of anti-EV71 neutralising antibody in the Older-B group (99.66%; 95% CI: 99.18%-100.00%) was non-inferior to that of the Older-C (99.32%; 95% CI: 98.65%-99.98%) and Younger-B groups (100.00%; 95% CI: 100.00%-100.00%). The differences in seroconversion rates in the Older-B group to those in the Older-C and Younger-B groups were 0.34% (95%CI: -2.17%-2.86%) and -0.34% (95%CI: -2.78%-2.09%). The GMT of the anti-EV71 neutralising antibody in the Older-B group (693.87) was also non-inferior to that in the Older-C (289.37) and Younger-B groups (634.80). The ratios of GMTs in the Older-B group to those in the Older-C and Younger-B groups were 2.67 (95%CI: 2.00-3.00) and 1.00 (95%CI: 0.75-1.00), respectively. The incidence of any adverse event (AE) related to vaccination was similar amongst the three groups (34/625 [5.44%] in the Older-B group, 32/623 [5.14%] in the Older-C group, and 26/349 [7.45%] in the Younger-B group), with only 2 (0.57%) participants having grade 3 AEs in the Younger-B group. Fifteen (0.94%) participants from these three groups had reported serious AEs (SAEs), all of which were unrelated to vaccines. Interpretation: EV71 vaccine produced by WIBP could extend to be administered to children aged 36-71 months against EV71 infection. However, the persistence of vaccine-induced immunities needs to be further investigated. Funding: Hubei Province's young medical talent program (20191229), Hubei Province's young talent program (2021), Hubei Province's young public health talent program (2021); and the Wuhan Institute of Biological Products Co., Ltd.

[Impact of antiretroviral therapy on drug-using and high risk sexual behaviors among HIV-positive methadone maintenance treatment clients: a qualitative study].

OBJECTIVE: To understand that whether initiation of antiretroviral therapy (ART) would impact on the change and its reasons regarding the HIV-related high risk behaviors among HIV-positive clients who attending the methadone maintenance treatment (MMT). METHODS: In-depth interviews were conducted among 34 MMT clients in Yunnan province who were under ART. The related contents would include information on general demographic charicteristics, HIV infection,MMT, number of sexual partners before and after ART, sexual behavior and frequency of condom use, drug use, needle sharing, changes in risk behaviors before and after the ART, reasons for high-risk behavior, of the clients. RESULTS: The average age of the interviewees was 38.5 years, and most of them were male (70.6%). The clients under this study all admitted that the frequencies of unsafe sex and needle sharing did not increase after the ART initiation, with the main reasons as increasing HIV related awareness, the use of methadone, high accessibility of free condoms and access to clean needles etc. However, 12 of 34 reported being relapsed and 3 reported inconsistent condom use. The interaction of ART and dosage of methadone were connected to the episodes of relapsing and the ART optimism would result in inconsistent condom use. CONCLUSION: No evidence supported that the ART initiation would increase the risk behaviors among the HIV-infected MMT clients. However, attention needs to be paid to the new challenges caused by high expectation of ART.