Replication, safety and immunogenicity of the vectored Ebola vaccine rVSV-ΔG-ZEBOV-GP in a sub-Saharan African paediatric population: A randomised controlled, open-label trial in children aged 1-12 years living in Lambaréné, Gabon

Article

作者: Kavishna, Ranmali ; Agnandji, Selidji T ; Velavan, Thirumalaisamy P ; Harandi, Ali M ; Musangomunei, Fungai P ; Olubiyi, Bisola F ; Rothenberger, Sylvia ; Nakaya, Helder I ; Siegrist, Claire-Anne ; Kabwende, Anita L ; Medaglini, Donata ; Kokou, Kossiwa ; Mahmoudou, Saidou ; Engler, Olivier ; Alabi, Ayodele ; Nakka, Sravya S ; Kremsner, Peter G ; Bie-Ondo, Juste C

BACKGROUNDUnlike adults, children experienced stronger and longer vector replication in plasma and shedding in saliva following rVSVΔG-ZEBOV-GP vaccination. The resulting risks of immunosuppression or immune hyperactivation leading to increased Adverse Events (AEs) and altered antibody responses are concerns that have been addressed in the present manuscript.METHODSChildren aged 1-12 years living in Gabon received either rVSVΔG-ZEBOV-GP (ERVEBO®) vaccine or the varicella-zoster virus (VZV) vaccine (VZV). The concentration of rVSVΔG vector in blood and saliva, the occurrence of AEs up to day 28; the anti-rVSVΔG-ZEBOV-GP and anti-VZV IgG antibody titres, neutralising and avidity functions of anti-rVSVΔG-ZEBOV-GP by day 365; were assessed in serum. (PACTR202005733552021) FINDINGS: In the rVSVΔG-ZEBOV-GP group, 70% and 7% of children had > 0 copies/ml of rVSVΔG respectively in plasma by day 3 and in saliva by day 14 after vaccination, with no detection on day 28. Significantly higher but transient AEs occurred in the rVSVΔG-ZEBOV-GP group. Both vaccines induced seroconversion on day 28 and sustainable IgG antibody titres by day 365. Avidity and neutralisation functions of the anti-rVSVΔG-ZEBOV-GP antibodies peaked at day 28 and were maintained by day 365.INTERPRETATIONThe replication and shedding do not affect the favourable risk-benefit balance of the rVSVΔG-ZEBOV-GP in children.FUNDINGThis trial is funded by the Innovative Medicines Initiative 2 (IMI 2) Joint Undertaking (grant number: 116068). The Biomedicine and Social Sciences research team of CERMEL is funded by the European and Developing Countries Clinical Trials Partnership (EDCTP-TMA-SF-1946-VARSAF).

2019-11-01·Vaccine3区 · 医学

Safety of the rVSV ZEBOV vaccine against Ebola Zaire among frontline workers in Guinea

3区 · 医学

Article

作者: Grais, Rebecca F ; Faga, Elisabetta Maria ; Soumah, Aboubacar ; Juan-Giner, Aitana ; Tchaton, Marie ; Cisse, Mohamed ; Jemmy, Jean-Paul ; Boum, Yap

BACKGROUNDAs part of the ring vaccination trial in Guinea, Front Line Workers were invited to participate in a sub-study to provide additional information on the immunogenicity and safety of rVSVΔG/ZEBOV-GP. Here we summarize the information on the safety follow-up.METHODSAn open-label, non-randomized, immunogenicity evaluation of one dose of rVSVΔG/ZEBOV-GP was conducted in Conakry, Guinea between March 2015 and July 2016. Front-line workers refusing vaccination were invited to participate as a control group. Participants were followed for 3 months with a subset followed-up for 6 months after vaccination. Women becoming pregnant during the follow-up were followed until pregnancy outcome. Solicited and unsolicited adverse events were monitored at each contact with participants using standardized study forms.RESULTS2016 vaccinated participants and 99 controls were included in the safety cohort. On the 3 days post-vaccination visit adverse events were very common, with over 70% of participants reporting at least one adverse event. The most frequently reported symptoms were headache, fatigue, arthralgia, subjective fever and myalgia. Among participants that completed fever diaries (n = 887), post-vaccination fever was reported by 15.22%. Comparing to the unvaccinated group, local reaction, fatigue, headache, arthralgia, myalgia and subjective fever occurring within the first 3 days post-vaccination were statistically significantly different in the vaccinated group compared to the unvaccinated. A total of 8 Serious Adverse Events were identified during follow-up. 2 SAEs were related to pregnancy.CONCLUSIONSResults confirm that adverse events 3 days after vaccination with the rVSV candidate vaccine are common. The occurrence of fever is of particular concern in the context of ongoing Ebola transmission. Additional studies should address important data gaps regarding the use of the vaccine in pregnancy and other vulnerable populations.

2016-05-01·Journal of General Virology3区 · 医学

Vaccinia virus-free rescue of fluorescent replication-defective vesicular stomatitis virus and pseudotyping with Puumala virus glycoproteins for use in neutralization tests

3区 · 医学

Article

作者: Strandin, Tomas ; Plyusnin, Alexander ; Hepojoki, Jussi ; Lundkvist, Åke ; Paneth Iheozor-Ejiofor, Rommel ; Vapalahti, Olli ; Levanov, Lev

Puumala virus (PUUV) grows slowly in cell culture. To study antigenic properties of PUUV, an amenable method for their expression would be beneficial. To achieve this, a replication-defective recombinant vesicular stomatitis virus, rVSVΔG*EGFP, was rescued using BSRT7/5 and encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES)-enabled rescue plasmids. Using these particles, pseudotypes bearing PUUV Sotkamo strain glycoproteins were produced, with titres in the range 105-108, and were used in pseudotype focus reduction neutralization tests (pFRNTs) with neutralizing monoclonal antibodies and patient sera. The results were compared with those from orthodox focus reduction neutralization tests (oFRNTs) using native PUUV with the same samples and showed a strong positive correlation (rs = 0.82) between the methods. While developing the system we identified three amino acids which were mutated in the Vero E6 cell culture adapted PUUV prototype Sotkamo strain sequence, and changing these residues was critical for expression and neutralizing antibody binding of PUUV glycoproteins.

100 项与 rVSVΔG-JUNVGP 相关的药物交易

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