Project description:BACKGROUND:In 2003, severe acute respiratory syndrome (SARS) resulted in hundreds of infections and deaths globally. We aim to assess immunogenicity and protective efficacy of purified inactivated Vero-cell SARS vaccine in monkeys. METHODS:The cultures of SARS coronavirus (SARS-CoV) BJ-01 strain infected Vero cells were inactivated with beta-propiolactone. Sequential procedures, including ultrafiltration, gel filtration and ion exchange chromatography, were performed to obtain purified inactivated SARS vaccine. The purified SARS vaccine was analyzed with electron microscope, HPLC and Western blotting. We immunized three groups of cynomolgus macaques fascicularis with adjuvant-containing purified vaccine, purified vaccine and unpurified vaccine, respectively, and a fourth group served as a control. Antibody titers were measured by plaque reduction neutralization test. The vaccinated monkeys were challenged with SARS-CoV BJ-01 strain to observe protective efficacy. Additionally, three groups of rhesus monkeys were immunized with different doses of the purified inactivated SARS vaccine (0.5, 1 and 2mug/time/monkey) on days 0 and 7, and the monkeys were challenged with SARS-CoV GZ-01 strain. We assessed the safety of the SARS vaccine and observed whether the antibody dependent enhancement (ADE) occurred under low levels of neutralizing antibody in rhesus. FINDINGS:The purity of SARS vaccine was 97.6% by HPLC identification and reacted with convalescent sera of SARS patients. The purified SARS vaccine induced high levels of neutralizing antibodies and prevented the replication of SARS-CoV in monkeys. Under low levels of neutralizing antibody, no exacerbation of clinical symptoms was observed when the immunized monkeys were challenged with SARS-CoV. In this preliminary animal trial, no side effects were detected when monkeys were immunized with purified SARS vaccine either at normal or large doses. INTERPRETATION:The purified inactivated SARS vaccine could induce high levels of neutralizing antibody, and protect the monkeys from the challenge of SARS-CoV. The SARS vaccine prepared in the study appeared to be safe in monkeys.

Project description:BACKGROUND:A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings. METHODS:We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 ?g ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909, NCT02952833, and NCT02937233. FINDINGS:We enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre ?1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies. INTERPRETATION:The ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults. FUNDING:Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases.

Project description:BACKGROUND:Standard-dose, seasonal, trivalent, inactivated influenza vaccine induces moderate-to-low haemagglutination-inhibition antibody responses in people living with HIV. This study assessed the immunogenicity and safety of different dosing schedules of inactivated influenza vaccine in pregnant women living with HIV in South Africa. METHODS:In this double-blind, randomised, controlled trial, we recruited pregnant women with HIV from seven antenatal clinics in Soweto, South Africa. Pregnant women were eligible if they were aged 18-38 years, infected with HIV, and had an estimated gestational age of 12-36 weeks. Women were randomly assigned (1:1:1), using a computer-generated randomisation list, to receive inactivated influenza vaccine containing 15 μg of each of the three seasonal influenza strains for that year, as a single dose, a double dose, or two single doses 1 month apart. Participants and study personnel were masked to group allocation. Haemagglutination-inhibition antibody responses were measured for all groups in the mothers at enrolment and at 1 month after each vaccine dose, and in the single-dose and double-dose groups within 7 days of birth in the neonates. Immunogenicity analyses only included women with visits 28-35 days apart and infants who were born at least 28 days after maternal immunisation. The primary was seroconversion rate to each of the vaccine strains in the mothers 1 month after completion of the dosing schedule, and the primary safety outcomes were frequency of local and systemic reactions. Safety was assessed in mothers and infants until 24 weeks post partum and analysed in all participants who received at least one dose of vaccine. This study is registered with ClinicalTrials.gov, NCT01527825, and is closed to accrual. FINDINGS:Between Feb 11, and June 6, 2013, 800 pregnant women living with HIV were enrolled and randomly assigned to the single-dose (n=266), double-dose (n=265), or two-single-doses (n=269) group. In the analysable population, seroconversion rates in mothers 1 month after the final vaccine dose were significantly higher in the double-dose group (n=230; ranging from 29% to 65% for the three vaccine strains) than in the single-dose group (n=230; ranging from 18% to 49%; p≤0·019 for the three vaccine strains), but were similar between the two-single-doses group (n=220; ranging from 23% to 52%) and the single-dose group (p≥0·20 for the three vaccine strains). Safety outcomes were similar in the three groups, except for more injection-site reactions in recipients in the double-dose group. INTERPRETATION:A regimen of double-dose inactivated influenza vaccine gave slightly greater immunogenicity than did a single-dose regimen in pregnant women living with HIV. However, immunogenicity in the double-dose group was still lower than historical data from the same setting in pregnant women without HIV. More immunogenic vaccines are needed for pregnant women living with HIV to enhance transplacental transfer of vaccine-induced protective antibodies to their newborn infants. FUNDING:Bill & Melinda Gates Foundation.

Project description:BackgroundWe assessed immunogenicity of three-dose and two-dose immunization schedules with a Sabin-strain inactivated poliovirus vaccine (sIPV) produced by one Chinese vaccine manufacturer.MethodsThis was an open label, randomized, controlled trial conducted in 16 vaccination clinics in Shandong province. Infants were allocated randomly to either a 3-dose study arm (sIPV administered at 2, 3, and 4 months of age) or a 2-dose arm (sIPV administered at 4 and 8-11 months of age). Poliovirus neutralizing antibodies were measured in sera collected prior to the first sIPV dose and one month after the last dose.FindingsWe enrolled 560 infants; 536 (95.7%) completed the study. Final seropositivity rates were >98% for all three serotypes in both study arms. There were no statistically significant differences in seropositivity between the 2-dose and the 3-dose schedule. Final median reciprocal titres of polio antibodies were high overall (>1:768 for all serotypes) and statistically significantly higher in 2-dose recipients compared with 3-dose recipients (p < 0.001).InterpretationThis study offers evidence that two doses of sIPV administered at 4 and 8-11 months of age and three doses of sIPV administered at 2, 3, and 4 months of age both provide serological protection against poliomyelitis. Median reciprocal titres of polio antibodies were high overall, and were more related to the interval between doses than the number of doses, with the longer interval of the 2-dose schedule producing higher reciprocal titres than the shorter-interval 3-dose schedule. The protection provided by the 3-dose schedule is achieved earlier in life than the protection with the 2-dose schedule. Countries planning to use an IPV-only schedule in the post-eradication era can consider this 2-dose sIPV option as an immunogenic and dose-sparing strategy.FundingWorld Health Organization (from a grant from International PolioPlus Committee, Rotary International, Evanston, IL, USA).

Dataset Information

Safety and immunogenicity of a Zika purified inactivated virus vaccine given via standard, accelerated, or shortened schedules: a single-centre, double-blind, sequential-group, randomised, placebo-controlled, phase 1 trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure