Safety and Immunogenicity of An Egg-Based Inactivated Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomized, Placebo-Controlled, Phase 1/2 Trial in Vietnam

Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus (NDV) vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1. The spike protein was stabilized and incorporated into NDV virions by removing the polybasic furin cleavage site, introducing the transmembrane domain and cytoplasmic tail of the fusion protein of NDV, and introducing six prolines for stabilization in the prefusion state. Vaccine production and clinical development was initiated in Vietnam, Thailand, and Brazil. Here the interim results from the first stage of the randomized, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial conducted at the Hanoi Medical University (Vietnam) are presented. Healthy adults aged 18-59 years, non-pregnant, and with self-reported negative history for SARS-CoV-2 infection were eligible. Participants were randomized to receive one of five treatments by intramuscular injection twice, 28 days apart: 1 g +/-CpG1018 (a toll-like receptor 9 agonist), 3 g alone, 10 g alone, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited adverse events (AEs) during 7 days and subject-reported AEs during 28 days after each vaccination. Investigators further reviewed subject-reported AEs. Secondary outcomes were immunogenicity measures (anti-spike immunoglobulin G [IgG] and pseudotyped virus neutralization). This interim analysis assessed safety 56 days after first vaccination (day 57) in treatment-exposed individuals and immunogenicity through 14 days after second vaccination (day 43) per protocol. Between March 15 and April 23, 2021, 224 individuals were screened and 120 were enrolled (25 per group for active vaccination and 20 for placebo). All subjects received two doses. The most common solicited AEs among those receiving active vaccine or placebo were all predominantly mild and included injection site pain or tenderness (<58%), fatigue or malaise (<22%), headache (<21%), and myalgia (<14%). No higher proportion of the solicited AEs were observed for any group of active vaccine. The proportion reporting vaccine-related AEs during the 28 days after either vaccination ranged from 4% to 8% among vaccine groups and was 5% in controls. No vaccine-related serious adverse event occurred. The immune response in the 10 g formulation group was highest, followed by 1 g +CpG1018, 3 g, and 1 g formulations. Fourteen days after the second vaccination, the geometric mean concentrations (GMC) of 50% neutralizing antibody against the homologous Wuhan-Hu-1 pseudovirus ranged from 56.07 IU/mL (1 g, 95% CI 37.01, 84.94) to 246.19 IU/mL (10 g, 95% CI 151.97, 398.82), with 84% to 96% of vaccine groups attaining a [≥] 4-fold increase over baseline. This was compared to a panel of human convalescent sera (N=29, 72.93 95% CI 33.00-161.14). Live virus neutralization to the B.1.617.2 (Delta) variant of concern was reduced but in line with observations for vaccines currently in use. Since the adjuvant has shown modest benefit, GMC ratio of 2.56 (95% CI, 1.4 - 4.6) for 1 g +/-CpG1018, a decision was made not to continue studying it with this vaccine. NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 g dose was advanced to phase 2 along with a 6 g dose. The 10 g dose was not selected for evaluation in phase 2 due to potential impact on manufacturing capacity. ClinicalTrials.gov NCT04830800.

The status of multidrug resistance in ubiqutous and dominated pseudomonas aeruginosa in Ha Noi hospital

Background: Strains caused by hospital-acquired infections as acommon rule havehigh multiantimicrobial resistance andincrease the dispersal risks ofthese strains. Objectives: To learn about the status of multidrug resistance in ubiquitous and dominant pseudomonas aeruginosa in Ha Noi hospital. Subjects and method: 138nosocomial Pseudomonas aerug.\r\n', u'Results:114 nosocomial Pseudomonas aerug- inosa isolates from Hanoi hospital were studied in relation to their antibiotic susceptibilities and the results showed the ratesof resistance to antibiotics among beta lactams ranged from 29 to 41.7%; quinolones ranged from 45.7% to 47.3%; cephems ranged from 64.1 % to 74.4% and aminoglyy cosides ranged from 41.1 to 74,6%. Of the five dominant serogroups O12 (27.2%); O11 (18.4%); O16 (11.4%); O5 (6.1%) and O2 (5.3%). Multidrug resistance rates in the major serogroups were O16 (100%); O11 (95.2%); and O12 (93.5%).Conclusion: Efforts to monitor antibiotic resistance of hospital bacteria strainsnationalwide, regional and local levels is necessary to provide physicians with the selection of information for effective treatment. \r\n', u'\r\n', u'

The status of multidrug resistance in ubiquitous and domination acinetobacter Spp caused nosocomial infections

Background: Acinetobacter spp are present everywhere in the environment and cause many epidemics in tropical countries.\r\n', u'Objectives: This study aims to learn about the status of multidrug resistance in ubiquitous and domination acinetobacter Spp caused nosocomial infections. Subjects and method: A descriptive, epidemiologic cross-sectional study on 65 nosocomial Acinetobacter spp isolated from 244 patients hospitalized at the intensive-care units, Bach Mai hospital and burn patients from the National Burn Institute from April, 2007 to May, 2008. Results: Rates of A.baumannii were 70.8% of the isolates. Acinetobacter spp were isolated from patients in intensive-care units showed resistant to almost all commercially available antibiotics groups, among Penicillin ranged from 94.6 to 97.4%; beta- Lactam ranged from 80.5 to 90%; Cephems were 97.6%; Aminoglycosides group ranged from 62.5 to 100% and Quinolon were 100%. The isolates that were susceptible to Netilmycin was 35% and Imipenem was 34.1%. Acinetobacter spp were isolated from burn patients, which showed resistant to Penicillin was 86, 7%; beta- Lactam was 93, 3%; Aminoglyco- sides ranged from 25% to 87.5% and Quinolon was 81,3%. The isolates were susceptible to Netilmycin was 75% and Imipenem was 31.3%. \r\n', u'Conclusion: Analysis of risk factors may help the study of epidemiology Acinetobacter to prevent hospital infections and reduce the mortality rate. \r\n', u'

Antimicrobial resistance and serotype distribution of streptococcus pneumonia isolates among children under 5 years of age, Hai Phong city, Viet Nam, during the period of 2006- 2007

Background: Streptococcus pneumonia (S.pneumoniae) is the main cause of acquired pneumonia in the community along with otitis media, sinusitis, septicemia and meningitis. Objectives: The study determined antimicrobial resistance and serotype distribution of Streptococcus pneumonia isolates from hospitalized children at Hai Phong Children's Hospital, Vietnam. Subjects and method: From June 2006 to September 2007, 80 pneumococccal isolates were tested for susceptibility to the 13 antibiotics and 84 pneumococcal isolates were serotyped. Results:Seventy-five percent of strains showed multi-drug resistance. Ninety percent of strains showed resistance to penicillin (48% intermediate and 42% fully resistant). In addition, 100% of isolates were resistant to cotrimoxazole, 74% of isolates were resistant to cephalexin; 71 % of isolates were resistant to erythroomycin and 58% were resistant to cefuroxxime. Almost all the isolates were susceptible to amoxicillin, cefotaxime, ceftriaxone, ceefepime, ofloxacin and 100% of isolates were susceptible to vancomycin. Among the 84 serotypes, 82% were included in the 23 valent pneumococcal polysaccharide vaccine including: 19F (30%), 23F (21 %), 14 (13%) and 6B (13%). Six other serotypes (13, 15C, 18, 11A, 15B and 6A) accounted for 12% of strains and 9 (11%) strains were untypeable. Conclusion: Pneumococcal antibiotics is spreading most rapidly among children in Vietnam, especially strains typs 19F and 23 F. Concerted efforts are necessary to prevent it spreading.\r\n", u'\r\n', u'

The manpower and the demand for training in basic microbiology technique of centres for preventive medicine in North provinces and cities

Background: In the past decades, preventive medicine had achieved significant success by promoting the effective prevention. However, we were facing with the rising again of dangerous infectious diseases that had been controlled. Ministry of Health had approved the development support project for preventive medicine system to strengthen early detection and control diseases in time. Objectives: To survey the manpower and the demand for training in basic microbiology technique of Centres for preventive medicine. Subjects and method: Technicians of 29 centres for preventive medicine in North provinces were surveyed and the results were studied by the described cross method. Results: Number of technicians graduated difference, fluctuated from 3 to 14 person per unit. The women were 80.4%; men were 19.6%. The staff who have degrees of postgraduate was 5.3%; University graduated was 41.2%; middle-ranking was 53.6%. Their specialities were very different: medicine doctor was 15.2%; biologists were 8.8%. The rest were nurse, technicians convalesce nurse, Medical Public Health...(34.4%). Among the demand for obtain the train in Microbiology, basic and advance labiratory techniques, 19.4% were the requests for training in basic microbiology; 16.4% were for molecular technology; 21.4% were for bacterium isolate technology and 19.4% were for virus technology. Conclusion: The results were the basis of creating a appropriate technical training strategy to contribute to the success of the project.

Immune response of extra - pulmonary tuberculosis patients treated with chemotherapy plus immunotherapy

The cell-mediated immunity of extra-pulmonary tuberculosis patients was followed up during treatment with chemotherapy plus immunotherapy. The results showed that there was no significant difference between the group treated with chemotherapy and the group treated with chemotherapy plus immunotherapy

Characteristics of mutation on rpoB gene of rifampicin-resistant tuberculosis strains insolated in Ha Noi and Ho Chi Minh City

57 rifampicin-resistant tuberculosis strains isolated from Ha Noi Institute of Tuberculosis and Lung Diseases and Pham Ngoc Thach Tuberculosis Center of Ho Chi Minh City were involved in this study. The regimen included 2-month SHRZ and 4-month HR. All of these strains were resistant to rifampicin. It was found that rifampicin-resistant tuberculosis strains had mutations on rpoB gene. The mutation frequency of tuberculosis trains isolated from Ha Noi and Ho Chi Minh City was highest on 526 locus (55% and 41.6%, respectively) and 531 locus (30% and 33%, respectively).

Use of H.influenzae B and N.meningitis A/C vaccines at HaNoi. Vn J Prev Med 2001

A survey conducted from 1-2/2000 in the 7 urban districts of Hanoi, Vietnam showed that overall use rate for Hib vaccine among children under 5 year of age was 3.2% and coverage for meningoccoal vaccine was 1.4%.

Bacterial meningitis in Ha Noi, 2000-2002

Population-based epidemiologic surveillance for bacterial meningitis in Hanoi from 2000 to 2002. The population under surveillance consists of children under 5 years of age, living in Hanoi urban districts. The results showed that bacterial meningitis represents an important cause of infant and childhood morbidity in Vietnam.