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Background: In a randomized controlled study (NCT01622062) a 1-week, 4-site intradermal (ID, 4-4-4-0-0) post-exposure prophylaxis (PEP) rabies vaccination regimen with purified Vero cell rabies vaccine (PVRV, Verorab®, Sanofi Pasteur), either without (Group 1) or with (Group 2) purified equine rabies immunoglobulin (ERIG), patients in the Philippines achieved seroconversion rates at Day 14 that were non-inferior to that of the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with ERIG (Group 3). Presented here are the annual immunogenicity data up to five years after the last primary dose, and the immunogenicity and safety data following simulated PEP with single-visit, 4-site ID regimen., Methods: Rabies virus neutralizing antibodies (RVNA) were determined by rapid fluorescent focus inhibition test (RFFIT). Participants (n = 397) received simulated PEP vaccination ID at Year 5 and RVNAs were assessed at Day 11 post-vaccination., Results: Seroconversion rates (RVNA titres ≥ 0.5 IU/mL) during annual follow-up remained >95% in Group 1 and were relatively stable at 80-90% in Group 2, but decreased from 80% to 64% in Group 3. RVNA geometric mean titres (GMTs) in Group 1 were consistently higher than in the other two groups, and those in Group 3 were generally lower than in the other two groups. There was a clear anamnestic response to vaccination in all groups, with all participants achieving RVNA titres ≥ 0.5 IU/mL at Day 11 post-simulated PEP booster vaccination. There were no safety concerns raised during annual follow-up and with simulated post-exposure vaccination with PVRV., Conclusion: The shortened, 1-week, 4-site ID regimen with PVRV achieved persistently higher RVNA titres than the updated 2-site TRC regimen, and more participants remained seroprotected up to five years after the last dose of primary immunization. Simulated post-exposure with 4-site ID rapidly induced an anamnestic response indicative of robust protection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BPQ has received research grants from Sanofi for other research studies on rabies. CA and SD have no conflicts of interest to declare. VBC, JK, CP, AR and GH are employees of Sanofi Pasteur., (Copyright © 2020 Sanofi Pasteur. Published by Elsevier Ltd.. All rights reserved.)

Background: Rabies post-exposure prophylaxis (PEP) via intradermal (ID) administration is standard practice in Asia. Accumulating evidence suggests that PEP shortened to 3 visits in one week does not adversely affect seroconversion rates or immune memory., Objective: To determine whether the seroconversion rate at Day14 with a 1-week, 4-site (4-4-4-0-0) ID vaccination regimen with or without rabies immunoglobulin (RIG) was non-inferior to the updated Thai Red Cross (TRC) 28-day, 2-site (2-2-2-0-2) ID regimen with RIG during rabies PEP. We also assessed one-year antibody persistence., Methods: This phase III, mono-center, open-label, randomized-controlled trial assigned participants aged ≤50 years (n = 600) exposed to suspected rabid animals and sustaining WHO Category II injuries (automatic allocation to G1) or Category III injuries (randomized to G2 or G3) to the following groups (1:1:1 ratio): G1 (n = 200), 1-week 4-site ID regimen with the purified Vero cell rabies vaccine (PVRV; Verorab®) without RIG; G2 (n = 201), 1-week 4-site ID regimen with PVRV, and purified equine rabies immunoglobulin (pERIG); G3 (n = 199), TRC 28-day, 2-site ID regimen with PVRV, and pERIG. Non-inferiority tests compared G1 vs. G3 and G2 vs. G3. Seroconversion rate was the proportion (%) of vaccinees with rabies virus neutralizing antibodies (RVNA) titers ≥0.5 IU/mL measured by rapid fluorescent focus inhibition test., Results: On Day14, after the third vaccine administration, seroconversion rates were non-inferior in both comparisons and were, respectively, 100%, 99.4%, 98.8% in G1, G2, G3 with a decrease to 97.6%, 89%, 79.8% at Year 1. At Day14, RVNA geometric mean titers were 11.3 IU/mL; 9.89 IU/mL; 6.15 IU/mL, respectively, decreasing to 2.96 IU/mL, 1.37 IU/mL, 0.97 IU/mL at Year1. Safety and tolerability were similar between the three groups., Conclusion: The seroconversion rate at Day 14 with the 1-week 4-site ID regimen, both with and without pERIG, was non-inferior to the reference TRC 28-day 2-site ID regimen with pERIG during rabies PEP with PVRV. ClinicalTrials.gov ID: NCT01622062., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children., Methods: This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to <5years in Thailand as a primary (Group 1) or booster (Group 2) vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described., Results: The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (<0.1%) in Group 2. There were no cases of Japanese encephalitis reported. No Grade 3 immediate systemic AEs were reported after any JE-CV vaccination., Conclusions: Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052)., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To consolidate the integration of the fragmented European vaccine development landscape, TRANSVAC - the European Network of Vaccine Research and Development, funded by the European Commission (EC) - has initiated the development of a roadmap through a process of stakeholder consultation. The outcome of this consultation highlighted the need for transnational cooperation and the opportunities that could be generated by such efforts. This cooperation can be achieved through the establishment of a European Vaccine Research and Development Infrastructure (EVRI). EVRI will support cooperation between existing vaccine Research and Development (R&D) organisations from the public and private sector and other networks throughout Europe. It will become sustainable over time by receiving support from multiple sources including the EC, European Union (EU) Member States, European vaccine companies, EVRI partner organisations, and by income generated. Different stakeholders have demonstrated support for the concept of a vaccine infrastructure and agree that such an infrastructure can function as leverage institution between public and private institutions thus making significant contributions to the vaccine field as a whole in its quest to develop vaccines. EVRI will be launched in three phases: preparatory (during which the legal and administrative framework will be defined and a business plan will be elaborated), implementation and operational. If sufficient political and financial commitment can be secured from relevant national and European entities as well as from the private sector and other stakeholders, it could enter into operational phase from 2017 onwards. In conclusion, EVRI can make vaccine R&D more efficient and help address European and global health challenges, help alleviate the burden and spread of infectious diseases, thus contributing to the sustainability of public healthcare systems., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)