Yellow fever vaccine (live) powder and solvent for suspension for injection 0.5ml vials

OBJECTIVE: To evaluate contraindications and precautions for the yellow fever vaccine (YFV) in risk populations. METHODS: A literature review was conducted by searching PubMed for "yellow fever vaccine" and "adverse events" (AEs); 207 studies were found, and 43 of them met the inclusion criteria and were included in a systematic review. RESULTS: do not have increased risk of AEs from YFV. Egg allergy vaccination protocols seem to provide a safe way to immunize these patients. CONCLUSIONS: YFV safety has been confirmed based on data from many vaccination campaigns and multiple studies. AEs seem more frequent after a first-time dose, mainly in risk groups, but this review evaluated YFV in several of the same risk groups and the vaccine was found to be safe in most of them.

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We conducted a systematic review and a meta-analysis to assess the risk of serious adverse events in the elderly after yellow fever vaccination compared to the non-elderly population. We searched multiple databases and grey literature, and we selected research without language and publication date restrictions. Studies were analyzed in a descriptive way and meta-analyzed and expressed in terms of prevalence ratio and risk ratio with a 95% confidence interval, depending on the degree of heterogeneity found. A total of 18 studies were included and 11 were meta-analyzed. The results obtained through the meta-analysis showed a risk of serious adverse events after yellow fever vaccination three times higher for the elderly when compared to the non-elderly population and five times higher for persons > 70 years. In relation to adverse event types, viscerotropic disease associated with the yellow fever vaccine had a risk that was six times higher when compared to the population < 60 years. The evidence found supports that the vaccine indication in individuals > 60 years of age should be based on a careful analysis of individual benefit-risk assessments. The results found suggest a higher risk of events for individuals > 70 years, especially for viscerotropic and neurotropic disease associated with YFV contraindicating the use of the YFV in this age group.

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BACKGROUND: The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. METHODS: We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. FINDINGS: Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7]; serotype 2, 0·0% [-2·1 to 2·1]; serotype 3, 0·0% [-3·8 to 3·9]). Poliovirus seroprevalence was universally high (>97%) after vaccination, but the antibody titres generated by fractional intradermal doses of IPV did not achieve non-inferiority compared with full dose. The number of infants who seroconverted or had a four-fold rise in titres was also lower by the intradermal route. There were no safety concerns. INTERPRETATION: The data support the future co-administration of IPV, measles-rubella, and yellow fever vaccines within the Expanded Programme on Immunization schedule at 9 months. The administration of single fractional intradermal doses of IPV by needle and syringe or disposable-syringe jet injector compromises the immunity generated, although it results in a high post-vaccination poliovirus seroprevalence. FUNDING: Bill & Melinda Gates Foundation.

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BackgroundEvidence indicates that fractional doses of yellow fever vaccine are safe and sufficiently immunogenic for use during yellow fever outbreaks. However, there are no data on the generalisability of this observation to populations living with HIV. Therefore, we aimed to evaluate the immunogenicity of fractional and standard doses of yellow fever vaccine in HIV-positive adults.MethodsWe conducted a randomised, double-blind, non-inferiority substudy in Kilifi, coastal Kenya to compare the immunogenicity and safety of a fractional dose (one-fifth of the standard dose) versus the standard dose of 17D-213 yellow fever vaccine among HIV-positive volunteers. HIV-positive participants aged 18–59 years, with baseline CD4+ T-cell count of at least 200 cells per mL, and who were not pregnant, had no previous history of yellow fever vaccination or infection, and had no contraindication for yellow fever vaccination were recruited from the community. Participants were randomly assigned 1:1 in blocks (variable block sizes) to either a fractional dose or a standard dose of the 17D-213 yellow fever vaccine. Vaccines were administered subcutaneously by an unblinded nurse and pharmacist; all other study personnel were blinded to the vaccine allocation. The primary outcome of the study was the proportion of participants who seroconverted by the plaque reduction neutralisation test (PRNT50) 28 days after vaccination for the fractional dose versus the standard dose in the per-protocol population. Secondary outcomes were assessment of adverse events and immunogenicity during the 1-year follow-up period. Participants were considered to have seroconverted if the post-vaccination antibody titre was at least 4 times greater than the pre-vaccination titre. We set a non-inferiority margin of not less than a 17% decrease in seroconversion in the fractional dose compared with the standard dose. This study is registered with ClinicalTrials.gov, NCT02991495.FindingsBetween Jan 29, 2019, and May 17, 2019, 303 participants were screened, and 250 participants were included and vaccinated; 126 participants were assigned to the fractional dose and 124 to the standard dose. 28 days after vaccination, 112 (96%, 95% CI 90–99) of 117 participants in the fractional dose group and 115 (98%, 94–100) of 117 in the standard dose group seroconverted by PRNT50. The difference in seroconversion between the fractional dose and the standard dose was –3% (95% CI –7 to 2). Fractional dosing therefore met the non-inferiority criterion, and non-inferiority was maintained for 1 year. The most common adverse events were headache (n=31 [12%]), fatigue (n=23 [9%]), myalgia (n=23 [9%]), and cough (n=14 [6%]). Reported adverse events were either mild (182 [97%] of 187 adverse events) or moderate (5 [3%]) and were self-limiting.InterpretationFractional doses of the 17D-213 yellow fever vaccine were sufficiently immunogenic and safe demonstrating non-inferiority to the standard vaccine dose in HIV-infected individuals with CD4+ T cell counts of at least 200 cells per mL. These results provide confidence that fractional dose recommendations are applicable to populations with high HIV prevalence.FundingWellcome Trust, Médecins Sans Frontières Foundation, and the UK Department for International Development.

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Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0–10 weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9 months (1 + 1 co-administration) or YF vaccine administered separately at age 10 months (1 + 1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9 months (3 + 0 separate). Blood samples were collected 28–35 days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres ≥ 1:8 were calculated with 95 % confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than − 10 %. Forty-eight, 66, and 98 participants enrolled in 3 + 0 separate, 1 + 1 co-administration, and 1 + 1 separate groups respectively had NA results. Per protocol analysis of the 3 + 0 separate, 1 + 1 co-administration, 1 + 1 separate, and the combined 1 + 1 separate and 3 + 0 separate groups found that 81 %, 85 %, 92 %, and 88 % of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1 + 1 co-administration and 1 + 1 separate groups was −7 % (95 % CI, −18 % to 3 %). The difference between 1 + 1 co-administration and 3 + 0 separate groups was 4 % (95 % CI, −10 % to 15 %). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9 months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613. • Overall, 86 % of participants had YF NA titres ≥1:8 at 1 month (mo) post-YF vaccination (YFV) • 81 %, 92 %, & 85 % of infants who received YFV separately at 9 & 10 mo, and YFV/PCV at 9 mo respectively had YF NA titres ≥1:8 • PCV13 co-administered with YF vaccine at 9 mo does not affect seroresponse to YF vaccine. • The difference in proportions comparing YFV/PCV co-administered at 9 mo and YFV given separately at 10 mo was −7 % • There was no statistical difference in the YF seroresponse when the YFV was co-administered with PCV or administered separately

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Yellow fever (YF) virus is a mosquito-borne flavivirus found in Sub-Saharan Africa and tropical South America. The virus causes YF, a viral hemorrhagic fever, which can be prevented by a live-attenuated vaccine, strain 17D. Despite the vaccine being very successful at decreasing disease risk, YF is considered a re-emerging disease due to the increased numbers of cases in the last 30 years. Until 2014, the vaccine was recommended to be administered with boosters every 10 years, but in 2014 the World Health Organization recommended removal of booster doses for all except special populations. This recommendation has been questioned and there have been reports of waning antibody titers in adults over time and more recently in pediatric populations. Clearly, the potential of waning antibody titers is a very important issue that needs to be carefully evaluated. In this Perspective, we review what is known about the correlate of protection for full-dose YF vaccine, current information on waning antibody titers, and gaps in knowledge. Overall, fundamental questions exist on the durability of protective immunity induced by YF vaccine, but interpretation of studies is complicated by the use of different assays and different cut-offs to measure seroprotective immunity, and differing results among certain endemic versus non-endemic populations. Notwithstanding the above, there are few well-characterized reports of vaccine failures, which one would expect to observe potentially more with the re-emergence of a severe disease. Overall, there is a need to improve YF disease surveillance, increase primary vaccination coverage rates in at-risk populations, and expand our understanding of the mechanism of protection of YF vaccine.

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Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the disease and the potential for importation to areas in Asia with ecological conditions that can sustain yellow fever virus transmission. In this article, we provide a broad overview of yellow fever burden of disease, natural history, treatment, vaccine, prevention and control initiatives, and vaccine and therapeutic agent development efforts.

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