Cross-protective capacity of Japanese encephalitis (JE) vaccines against circulating heterologous JE virus genotypes.

Current Japanese encephalitis vaccines are derived from strains of genotype III, yet heterologous genotypes are emerging in endemic areas. Inactivated vaccines given to European travelers were found to elicit protective levels of neutralizing antibodies against heterologous strains of genotypes I-IV.

Enhancing Public Health Communication Regarding Vaccine Trials: Design and Development of the Pan-European VACCELERATE Toolkit.

BACKGROUND: The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial-related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE: This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS: Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients' Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS: This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS: The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials.

A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines.

BACKGROUND: A significant part of the world population lives in areas with endemic Japanese encephalitis (JE). For travelers from nonendemic countries, Vero cell-derived vaccine (JE-VC; Ixiaro) has replaced traditional mouse brain-derived vaccines (JE-MB) associated with safety concerns. The 2 vaccines are derived from different viral strains: JE-VC from the SA14-14-2 strain and JE-MB from the Nakayama strain. No data exist regarding whether JE-VC can be used to boost immunity after a primary series of JE-MB; therefore, a primary series of JE-VC has been recommended to all travelers regardless of previous vaccination history. METHODS: One hundred twenty travelers were divided into 4 groups: Volunteers with no prior JE vaccination received primary immunization with (group 1) JE-MB or (group 2) JE-VC, and those primed with JE-MB received a single booster dose of (group 3) JE-MB or (group 4) JE-VC. Immune responses were tested before and 4-8 weeks after vaccination using plaque reduction neutralization test (PRNT) against both vaccine strains. RESULTS: In vaccine-naive travelers, the vaccination response rate for test strains Nakayama and SA14-14-2 was 100% and 87% after primary vaccination with JE-MB and 87% and 94% after JE-VC, respectively. Antibody levels depended on the target virus, with higher titers against homologous than heterologous PRNT(50) target strain (P < .001). In travelers primed with JE-MB, vaccination response rates were 91% and 91%, and 98% and 95% after a booster dose of JE-MB or JE-VC, respectively. Subgroup analysis revealed that a higher proportion of primed (98%/95%) than nonprimed (39%/42%) volunteers responded to a single dose of JE-VC (P < .001). CONCLUSIONS: A single dose of JE-VC effectively boosted immunity in JE-MB-primed travelers. Current recommendations should be reevaluated. CLINICAL TRIALS REGISTRATION: NCT01386827.

Immunogenicity and safety of the tick-borne encephalitis vaccination (2009-2019): A systematic review.

BACKGROUND: Tick-borne encephalitis (TBE) is increasing in Europe. We aimed to evaluate the immunogenicity and safety of TBE-vaccination. METHODS: This systematic review was registered at PROSPERO (#CRD42020155737) and conducted in accordance with PRISMA guidelines. We searched CINAHL, Cochrane, Embase, PubMed, and Scopus using specific terms. Original articles, case reports and research abstracts in English, French, German and Italian were included for screening and extracting (JER; PS). RESULTS: Of a total of 2464 records, 49 original research publications were evaluated for immunogenicity and safety. TBE-vaccines showed adequate immunogenicity, good safety and interchangeability in adults and children with some differences in long-term protection (Seropositivity in 90.6-100% after primary vaccination; 84.9%-99.4% at 5 year follow up). Primary conventional vaccination schedule (days 0, 28, and 300) demonstrated the best immunogenic results (99-100% of seropositivity). Mixed brand primary vaccination presented adequate safety and immunogenicity with some exceptions. After booster follow-ups, accelerated conventional and rapid vaccination schedules were shown to be comparable in terms of immunogenicity and safety. First booster vaccinations five years after primary vaccination were protective in adults aged <50 years, leading to protective antibody levels from at least 5 years up to 10 years after booster vaccination. In older vaccinees, > 50 years, lower protective antibody titers were found. Allergic individuals showed an adequate response and immunosuppressed individuals a diminished response to TBE-vaccination. CONCLUSIONS: The TBE-vaccination is generally safe with rare serious adverse events. Schedules should, if possible, use the same vaccine brand (non-mixed). TBE-vaccines are immunogenic in terms of antibody response but less so when vaccination is started after the age of 50 years. Age at priming is a key factor in the duration of protection.

Tick borne encephalitis (TBE)-vaccination coverage and analysis of variables associated with vaccination, Sweden.

To estimate the tick borne encephalitis (TBE)-vaccination coverage in the greater Stockholm region, we sent a questionnaire to a randomized sample of 8000 individuals in 2013. Fifty-three percent of all respondents (n=4307) reported being vaccinated against TBE at least once. Reasons for not vaccinating included: no perceived risk (28.6%), too expensive (25.6%), did not have the time or opportunity (23%) and worried about vaccine side-effects (20.5%). Multiple logistic regression revealed that the probability of being vaccinated was higher among those who reported ≥2 weeks outdoor exposure in a known high risk area (OR 4.13 95% CI 3.54-4.81) and in individuals ≥60 years of age compared to all other age groups (OR 0.67 95% CI 0.55-0.81). A high net household income was associated with a higher probability of being vaccinated (OR 2.10 95% CI 1.6-2.73). Being born outside Europe was negatively correlated (OR 0.57 95% CI 0.39-0.83). Based on our findings the estimated TBE-incidence in the unvaccinated regional population was 8.5-12/100,000 which is comparable with high endemic areas as the Baltic region and Central Europe. We suggest targeted vaccination and reimbursement strategies in high-endemic areas of Sweden. Our results indicate a need for improved public information about TBE.

Cross-protection elicited by primary and booster vaccinations against Japanese encephalitis: a two-year follow-up study.

BACKGROUND: The inactivated Vero cell-derived vaccine (JE-VC, IXIARO) has replaced the traditional mouse brain-derived preparations (JE-MB) in travelers' vaccinations against Japanese encephalitis. We showed recently that a single JE-VC dose efficiently boosts immunity in JE-MB-primed vaccinees, and that JE-VC elicits cross-protective immunity against non-vaccine genotypes, including the emerging genotype I. While these studies only provided short-term data, the present investigation evaluates the longevity of seroprotection in the same volunteers. METHODS: The study comprised 48 travelers who had received (1) JE-VC primary series, (2) JE-MB primary series followed by a single JE-VC booster dose, or (3) JE-MB primary series and a single JE-MB booster dose. Serum samples were collected two years after the last vaccine dose, and evaluated with the plaque-reduction neutralization test against seven Japanese encephalitis virus strains representing genotypes I-IV. PRNT50 titers ≥ 10 were considered protective. RESULTS: Two years after the primary series with JE-VC, 87-93% of the vaccinees proved to be cross-protected against test strains representing genotypes II-IV and 73% against those of genotype I. After a single homologous or heterologous booster dose to JE-MB-primed subjects, the two-year seroprotection rates against genotype I-IV strains were 89-100%. CONCLUSIONS: After JE-VC primary series, seroprotection appeared to wane first against genotype I. The first booster should not be delayed beyond two years. In JE-MB-primed subjects, a single JE-VC booster provided cross-protective immunity against genotype I-IV strains in almost all vaccinees, suggesting an interval of two years or even longer for the second booster. These data further support the use of a single JE-VC dose for boosting JE-MB immunity.

Malaria risk in travelers.

Imported malaria has been an increasing problem in several Western countries in the last 2 decades. To calculate the risk factors of age, sex, and travel destination in Swedish travelers, we used data from the routine reporting system for malaria (mixture of patients with and without adequate prophylaxis), a database on travel patterns, and in-flight or visa data on Swedish travelers of 1997 to 2003. The crude risk for travelers varied from 1 per 100,000 travelers to Central America and the Caribbean to 357 per 100,000 in central Africa. Travelers to East Africa had the highest adjusted odds ratio (OR = 341, 95% confidence intervals [CI] 134-886) for being reported with malaria, closely followed by travelers to central Africa and West Africa. Male travelers as well as children <1-6 years of age had a higher risk of being reported with malaria (OR = 1.7, 95% CI 1.3-2.3 and OR = 4.8, 95% CI 1.5-14.8) than women and other age groups.

Travellers returning to Sweden with falciparum malaria: pre-travel advice, behaviour, chemoprophylaxis and diagnostic delay.

We have investigated pre-travel advice, behaviour, chemoprophylaxis and diagnostic delay in travellers returning to Sweden with falciparum malaria. Questionnaires were distributed to patients having been notified with falciparum malaria from 1994 to 2001. Of 408 notified patients, 237 (58%) returned the questionnaires; 62% were males and 43% above the age of 45 y. Africa was the travel destination in 90% of the cases, and 27% had travelled to Kenya. 69% had spent more than 1 night in the countryside, and 6% had stayed in modern urban areas only. 40% took an adequate dose of chemoprophylaxis, although this proportion decreased from 55% to 12% during the study period. Nine per cent used both bed nets and mosquito repellents regularly. The median time from onset of symptoms to contact with health care professionals was 2 d, and from that contact to start of malaria treatment the median time was less than 24 h.