Fever Vaccine Research Articles

Q fever prevention: Perspectives from university animal science and veterinary students and livestock farmers.

To explore animal science and veterinary students' and livestock farmers' perceptions concerning Q fever prevention. An online survey with an open-ended question seeking knowledge and perceptions about Q fever prevention was distributed among participants during March-September 2019. We applied thematic analysis to identify emerging themes. Animal science and veterinary students enrolled at the University of Adelaide and members of Livestock South Australia representing cattle, sheep and goat farmers in South Australia. A total of56 animal science and veterinary students and 154 livestock farmers responded to the open-ended question. Not applicable. Perceived challenges and opportunities for a coordinated Q fever prevention approach including human vaccination reported by the participants. Two major themes arose in each group. Students and farmers viewed Q fever vaccination as important. However, excessive cost for students was a barrier and for farmers, it was general practitioners' lack of knowledge of Q fever and access to an accredited immunisation provider. Similarly, both groups highlighted the need for education and increasing public and community awareness of Q fever. Our findings underscore that a sector-wide approach involving community awareness programmes, education and training for general practitioners, and subsidised vaccination as well as commitment from government and industry partners may contribute to reducing the burden of Q fever among at-risk populations.

A molecular atlas of innate immunity to adjuvanted and live attenuated vaccines, in mice.

Adjuvants hold great potential in enhancing vaccine efficacy, making the understanding and improving of adjuvants critical goals in vaccinology. The TLR7/8 agonist, 3M-052, induces long-lived humoral immunity in non-human primates and is currently being evaluated in human clinical trials. However, the innate mechanisms of 3M-052 have not been fully characterized. Here, we perform flow cytometry, single cell RNA-seq and ATAC-seq to profile the kinetics, transcriptomics and epigenomics of innate immune cells in murine draining lymph nodes following 3M-052-Alum/Ovalbumin immunization. We find that 3M-052-Alum/OVA induces a robust antiviral and interferon gene program, similar to the yellow fever vaccine, which is known to confer long-lasting protection. Activation of myeloid cells in dLNs persists through day 28 and single cell analysis reveals putative TF-gene regulatory programs in distinct myeloid cells and heterogeneity of monocytes. This study provides a comprehensive characterization of the transcriptomics and epigenomics of innate populations in the dLNs after vaccination.

Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens

Background: Because of yellow fever’s serious impact on health, vaccination is the principal strategy to control the disease. Administration of the yellow fever vaccine to breastfeeding women should be before they complete 9 months post-delivery, in order to prevent transmission of the yellow fever vaccine virus to their infants through breast feeding. This study aimed to confirm whether the excretion of yellow fever vaccine virus is in milk of vaccinated breastfeeding mothers and to confirm the probable transmission to their infants through breast milk. Methods: Samples were taken as follows: one serum specimen was taken 3-14 days after the date of the vaccination, and breast milk specimens were taken at four different time points between 3-4 days apart. Specimens were obtained from eight nursing mothers, who received the YVF vaccine (17DD). Mothers were asymptomatic before and after the vaccine administration but their infants developed symptoms after administration. Maternal serum samples were tested for YFV specific IgM antibodies through immuno-fluorescent assay (IFA). RNA was extracted from serum and breast milk specimens and YFV RNA screened using real-time polymerase chain reaction (RT-PCR). Results: In total, five mothers (62.5%) were positive for YFV and two mothers (25%) had YFV RNA in serum. Among milk specimens, YFV RNA was detected during the four different mentioned collection times as follows (positive milk specimens/total milk specimens): 3/8 (37.5 %), 4/6 (66.6%) and 1/4(25%). RNA was completely undetectable in the last collection time. Conclusions: YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother’s YF vaccination.

Pneumococcal conjugate vaccination schedules in infants\u2014acquisition, immunogenicity, and pneumococcal conjugate and yellow fever vaccine co-administration study

BackgroundPneumococcal conjugate vaccines (PCVs) effectively prevent pneumococcal disease, but the global impact of pneumococcal vaccination is hampered by its cost. The evaluation of reduced dose schedules of PCV includes measurement of effects on immunogenicity and carriage acquisition compared to standard schedules. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where the introduction of PCV resulted in good disease control but where transmission of vaccine-type pneumococci persists. We designed a large cluster-randomised field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. We will also conduct a sub-study to evaluate the individual-level effect of the two schedules on carriage acquisition, immunogenicity, and co-administration of PCV with yellow fever vaccine, the PVS-AcqImm trial.MethodsPVS-AcqImm is a prospective, cluster-randomised trial of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. alternative ‘1+1’ schedule) compared to three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. standard ‘3+0’ schedule). Sub-groups within the alternative schedule group will receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 9 to 14 months of age, (b) geometric mean concentration of vaccine-type pneumococcal IgG at 18 months of age, and (c) proportions with yellow fever neutralising antibody titre ≥8 four weeks after administration of yellow fever vaccine. Participants and field staff will not be masked to group allocation while the measurement of laboratory endpoints will be masked. Approximately equal numbers of participants will be resident in each of 28 geographic clusters (14 clusters in alternative and standard schedule groups); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements.DiscussionAnalysis will account for potential non-independence of measurements by cluster and so interpretation of effects will be at the individual level (i.e. a population of individuals). PVS-AcqImm will evaluate whether acquisition of vaccine-type pneumococci is reduced by the alternative compared to the standard schedule, which is required if the alternative schedule is to be effective. Likewise, evidence of superior immune response at 18 months of age and safety of PCV co-administration with yellow fever vaccine will support decision-making regarding the use of the alternative 1+1 schedule. Acquisition and immunogenicity outcomes will be essential for the interpretation of the results of the large field trial comparing the two schedules.Trial registrationInternational Standard Randomised Controlled Trial Number 72821613.

Immune interference revisited: Impact of live-attenuated influenza vaccine prior to yellow fever vaccination

BackgroundDuring routine mass live-attenuated influenza vaccination (LAIV) for military personnel, emergent deployment for Ebola humanitarian assistance (OUA) required mass yellow fever vaccination (YF17D), often < 4-weeks recommended timing post-LAIV—triggering concerns for immune interference. We compared YF17D seroconversion rates in personnel who received YF17D as recommended (vaccinated by guidelines [VBG]) to those who received the vaccine outside the recommended timing following LAIV (not vaccinated by guidelines [NVBG]). MethodsOUA deploying personnel who received LAIV simultaneously or before YF17D and had pre- and post-vaccination archived serum were included. VBG was defined as YF17D given concurrently or ≥ 30 days post-LAIV and NVBG as YF17D given 1–29 days post-LAIV. YF17D seroresponse was determined by screening ELISA confirmed with plaque reduction neutralization testing (PRNT) on positive ELISA samples. Exclusion criteria were prior YF17D and pre-vaccination YF17D positive PRNT. ResultsOf the 660 personnel included, 507 were VBG and 153 were NVBG. Median age was 25 years for both groups. Men accounted for 84% of those VBG and 79% NVBG (p = 0.194). Seroconversion rates were 97.8% for VBG and 95.4% for NVBG (p = 0.15). Multivariate logistic regression revealed that YF17D on days 7–21 post-LAIV (adjusted odds ratio [aOR] 0.304, p = 0.017; confidence interval [CI] 0.114–0.810) and female sex (aOR 0.330, p = 0.026; CI 0.124–0.879) were associated with decreased seroresponse. ConclusionsIn this healthy, young adult military population, there was high seroconversion following YF17D when administered simultaneously and at various time points after LAIV. Slight decreases in seroresponse were seen in women and those receiving YF17D 7–21 days following LAIV.

Health Problems Encountered by Short-Term European Volunteers in a Nongovernmental Organization in Cambodia.

Short-term volunteers are susceptible to a wide spectrum of morbidities, mostly infectious diseases preventable with general hygiene and preventive measures. This study aimed to identify the health problems encountered by European short-term volunteers collaborating for 1 month with a nongovernmental organization (NGO) in Cambodia and to describe their characteristics. A prospective, descriptive observational study was conducted on short-term volunteers who collaborated with an NGO in Cambodia during August 2018. Informed consent and sociodemographic, clinical, and preventative health-related questionnaire data were provided by 198 volunteers. The health problems encountered were confirmed in a primary care consultation with healthcare professionals. Univariate and bivariate analyses were performed. The median age of the volunteers was 22 years (interquartile range = 21-24), and 64% were women. Some (18.2%) had allergies, 8.6% had preexisting health conditions, and 10.6% were under regular treatment. A total of 77.3% visited a pretravel consultation clinic, 39.9% completed a specific pretravel health course, 21.7% took malaria prophylaxis, 92.4% received hepatitis A vaccination, and 82.3% received typhoid fever vaccination. Medical assistance was sought by 112 (57.3%) of the volunteers. The average number of health problems was 2.5 (standard deviation = 1.5), and the total number of health problems attended by the medical team was 279. The most common health problems were upper respiratory infections (12.2 per 1,000 person/days), wounds (10.8 per 1,000 person/days), and diarrhea (6.3 per 1,000 person/days). Short-term volunteers experienced a high rate of health problems during their stay in Cambodia, but most of the problems were mild and preventable and resolved quickly. Pretravel consultation and specific pretravel health training seemed to increase disease awareness.

Yellow fever vaccine usage in the United States and risk of neurotropic and viscerotropic disease: A retrospective cohort study using three healthcare databases

BackgroundYellow fever (YF) vaccines are highly effective and have a well-established safety profile despite the risk of rare serious adverse events (SAEs), vaccine-associated neurotropic (YEL-AND) and viscerotropic disease (YEL-AVD). This study aimed to describe US civilian YF vaccine usage, the population characteristics and pre-existing immunosuppressive medical conditions among those vaccinated, and to provide updated risk estimates of neurotropic and viscerotropic disease post-vaccination. MethodsA retrospective cohort study was conducted using de-identified patient information from Optum Electronic Healthcare Record (EHR) (2007–2019), Optum Clinformatics Data Mart (CDM) (2004–2019) and IBM MarketScan (2007–2019) databases. YF vaccine recipients were identified using relevant vaccination and procedural codes. Demographic characteristics and pre-existing medical conditions were described. Incidence proportions with 95% confidence intervals (CI) of neurotropic and viscerotropic diseases occurring ≤ 30 days post-vaccination, after exclusion of unlikely cases based on current clinical guidelines of YEL-AND and YEL-AVD, were calculated. ResultsA total of 92,205, 46,539 and 125,235 YF vaccine recipients were retrieved from Optum EHR, Optum CDM and IBM MarketScan databases, respectively. The majority of vaccine recipients were aged < 60 years (highest proportion aged 18–29 years) with a higher proportion of females overall. Few vaccine recipients (<1%) had conditions predisposing them to immunosuppression. Four non-fatal cases of neurotropic disease and zero cases of viscerotropic disease were identified. The incidence proportion of post-vaccination neurotropic disease was 1.41 (95% CI: 0.15–6.61) and 3.04 (95% CI: 0.86–8.11) per 100,000 vaccine recipients in Optum EHR and IBM MarketScan, respectively, with no events identified in Optum CDM. ConclusionsThis study provides updated insights into current YF vaccine usage in US civilian recipients and supports the safety profile of YF vaccines in US practice. The low frequency of pre-existing immunosuppressive medical conditions among vaccine recipients suggests good adherence to vaccination guidelines by healthcare practitioners. The risk of developing neurotropic and viscerotropic disease post-vaccination remains rare.

Establishment of an Alternative Method for Determination of Protective Dose50 of Classical Swine Fever Vaccines

Establishment of an Alternative Method for Determination of Protective Dose50 of Classical Swine Fever Vaccines

Missed Opportunities for Vaccination and Associated Factors among Children Aged 12 - 23 Months in Cameroon: Further Analyses of 2018 Cameroon Demographic and Health Survey

Background: Low vaccination coverage has been attributed to missed opportunities for vaccination (MOV). This study examines the prevalence of MOV, and its associated factors among children in Cameroon. Methods: Data from the 2018 Demographic and Health Survey (DHS) was analyzed for children with at least one vaccination date in the home-based record (HBR). Immunization performances such as accessibility, drop-out, and timeliness, were assessed. Service quality was assessed using MOV. Multiple logistic regression examined the effect of DHS variables on MOV outcomes, and a decision tree approach was used to study their interaction. Results: Overall, 1824 children aged 12 to 23 months were surveyed; 1285 (70.45%) had cards seen with vaccination dates leading to 85.03% of immunization activities. A proportion of 46.5% of children were not completely vaccinated. There was 27% of drop-out between BCG and MCV1, and less than 10% with the specific antigens. Vaccination timeliness proportions ranged from 42.18% for BGC to less than 70% for PENTA1-3. The national prevalence of MOV for simultaneous vaccines was 75.1% (95% confidence interval (CI) = 72; 79). Among those who experienced MOV, 67.4% (95% CI = 60 - 73) were uncorrected MOV. MOV was an issue in all regions and comparable in rural areas that urban areas (p = 0.2). Dose-specific MOV ranged from 2.66% (for the third dose of the pneumococcal conjugate vaccine) to 91.12 (for the yellow fever vaccine). Second birth order children experienced more MOV than first born children (adjusted odds ratio (aOR) = 1.67, 95% CI: 1.11 - 2.47). Children born to non-educated/primary level mothers had increased odds of experiencing a MOV than those born to educated mothers (aOR = 1.48, 95% CI = 1.007 - 2.19/aOR = 1.55, 95% CI = 1.12 - 2.09). Children from poorest households were at high risk of experiencing MOV for any vaccine than richest households (aOR = 2.04, 95% CI = 1.11 - 3.76). Conclusion: There is a burden of MOV and under immunized children in the population. Direct interventions that target rural poor and focus on equity gaps that relate to maternal education, socio-economic status, and family planning, should be implemented. Such strategies should aim at reducing MOV for the achievement of the immunization agenda 2030 goals.

Effect of the Timing of Vaccination in Pregnant Sows and Colostral Restriction for Neonatal Piglets on the Level of Transmission of Maternal Antibodies for Classical Swine Fever Vaccine to Suckling Piglets

Effect of the Timing of Vaccination in Pregnant Sows and Colostral Restriction for Neonatal Piglets on the Level of Transmission of Maternal Antibodies for Classical Swine Fever Vaccine to Suckling Piglets

Immediate adverse events to the yellow fever vaccine in egg-allergic children

Immediate adverse events to the yellow fever vaccine in egg-allergic children

Shared acute phase traits in effector and memory human CD8 T cells

CD8 T cells have multiple functional properties that mediate acute phase and long-term immune protection. Several effector and memory CD8 T cell subsets have been described with diverse functionalities and marker profiles. In contrast to the many comprehensive mouse studies, most human studies lack samples from the acute infection phase, a major reason why current knowledge of human T cell subsets and differentiation remains incomplete, particularly with regard to the T cell heterogeneity early during the immune response. Here we analysed the human CD8 T cell response to yellow fever vaccination as the best-known model to study the human immune response to acute viral infection. We performed flow cytometry on 21 markers conventionally used in mice and in humans to describe differentiation, activation, cycling, and so-called effector functions. We found clearly distinct ‘acute traits’ at the peak of the response that are shared amongst all non-naïve antigen-specific subsets, including memory-differentiated cells. These acute traits were low BCL-2 and high KI67, CD38, HLA-DR, as well as increased Granzyme B and Perforin, previously attributed only to effector cells at the peak of the response. Furthermore, analysis of chromatin accessibility at the single cell level revealed that memory- and effector-differentiated cells clustered together specifically in the acute phase. Altogether, we demonstrate ‘acute traits’ across differentiation subsets, and point out the need to discriminate the differentiation states when studying human CD8 T cells that undergo an acute response.

Exploratory study of humoral and cellular immunity to 17DD Yellow Fever vaccination in children and adults residents of areas without circulation of Yellow Fever Virus

The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9Mths–4Yrs and 288 adults/18–49Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9Mths–2Yrs). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9Mths–2Yrs) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9Mths–2Yrs). Biomarker signatures further support that only Younger Children (9Mths–2Yrs) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination.

Vaccine Passport Use and Travel Health Status Among Turkish Travelers at an International Airport

Introduction: Even though Istanbul is one of the centers of the world’s fastest-growing tourism and travel sector, there are limited statistics on the knowledge, attitudes, and practices (KAP) of travelers from this region regarding travel-related infectious diseases. This study aimed to determine the passengers’ KAP about contagious diseases and contribute to developing new solutions for the problems people face while traveling abroad. Methods: A questionnaire was administered to 182 Turkish travelers planning on traveling abroad and applied to the Istanbul Travel Health Center and the Istanbul Airport Health Control Center between January and March 2019. Results: The proportion of carrying a vaccination certificate was statistically higher in those who received healthcare services at international terminals (P=0.002), especially those who had yellow fever (P&lt;0.001) and meningococcal vaccine (P=0.011). More than half of the vaccinated passengers did not carry their vaccination certificates, while around half (53.8%) were traveling to Africa. When compared to travelers flying to Europe, vaccination checks were 6.7 times (95% CI: 2.5-17.9) higher in passengers traveling to Africa, 6.1 times (95% CI: 1.5-24.3) higher in passengers traveling to Asia, and 14.8 times (95% CI: 1.3-164.3) higher in passengers traveling to South America. In addition, the vaccination certificate carrying proportion was significantly higher in those with a travel duration of 15 days or more (P=0.028), those who received health services at international terminals (P=0.002), and those vaccinated (P&lt;0.001). Conclusion: Improved knowledge of travel-related infectious diseases and increased adoption of pre-travel health advice and vaccines are urgently needed among Turkish travelers.

Yellow fever vaccination in Brazil: Short-term safety and immunogenicity in juvenile autoimmune rheumatic diseases

Yellow fever vaccine (YFV) is a live attenuated vaccine usually contraindicated for juvenile autoimmune rheumatic disease (JARD) patients. During the recent epidemic in Sao Paulo-Brazil, YFV was indicated for patients under low immunosuppression. Thirty JARD patients with inactive diseases undergoing low immunosuppression and 30 healthy controls (HC) were vaccinated with a fractional dose 17DD YFV (∼5495 IU) and evaluated 30 days later. JARD patients and controls had comparable median age (12.4 vs. 12 years, p = 0.250). Disease parameters remained stable 30 days after 17DD YFV (p > 0.05) and only mild adverse events were reported in both groups (p > 0.05). JARD and HC had similar seroprotection [93% vs. 100%;p = 0.49], seroconversion rates [96% vs. 100%;p = 0.489], and GMT [1249 vs.1293;p = 0.821]. Both groups had similar white-blood-cells kinetics with transient decreases in lymphocytes at D5 and neutrophils at D10, followed by full recovery at D30 (P < 0.05). In conclusion, 17DD YFV was safe and immunogenic in JARD. This study may contribute to recommendations for patients living/travelling to endemic areas.

Soluble antigens derived from Coxiella burnetii elicit protective immunity in three animal models without inducing hypersensitivity

SummaryQ fever is caused by the intracellular bacterium Coxiella burnetii, for which there is no approved vaccine in the United States. A formalin-inactivated whole-cell vaccine (WCV) from virulent C. burnetii NMI provides single-dose long-lived protection, but concerns remain over vaccine reactogenicity. We therefore sought an alternate approach by purifying native C. burnetii antigens from the clonally derived avirulent NMII strain. A soluble bacterial extract, termed Sol II, elicits high-titer, high-avidity antibodies and induces a CD4 T cell response that confers protection in naive mice. In addition, Sol II protects against pulmonary C. burnetii challenge in three animal models without inducing hypersensitivity. An NMI-derived extract, Sol I, enhances protection further and outperforms the WCV gold standard. Collectively, these data represent a promising approach to design highly effective, non-reactogenic Q fever vaccines.

New pre-vaccination checklist for yellow fever vaccine

New pre-vaccination checklist for yellow fever vaccine

Q fever vaccine development: Challenges and progress in balancing safety and efficacy

The existing human vaccine against Q fever, a zoonotic disease of biothreat concern, is approved only in Australia. In this issue of Cell Reports Medicine, Gregory and colleagues describe a new vaccine candidate that overcomes specific concerns hindering wider acceptance of the commercial vaccine.1

Safety of African Swine Fever Vaccine Candidate Lv17/WB/Rie1 in Wild Boar: Overdose and Repeated Doses.

African swine fever (ASF) is a highly lethal infectious disease that affects domestic pigs and wild boar. Outbreaks of ASF have grown considerably in the last decade causing important economic consequences for the swine industry. Its control is hampered by the lack of an effective treatment or vaccine. In Europe, the wild boar is a key wild reservoir for ASF. The results of the oral vaccination trial of wild boar with Lv17/WB/Rie1 are hope for this problem. However, this vaccine candidate has certain safety concerns, since it is a naturally attenuated vaccine. Therefore, the current study aims to evaluate the safety of this vaccine candidate in terms of overdose (high dose) and repeated doses (revaccination) in wild boar. Low-dose orally vaccinated animals developed only a slight transient fever after vaccination and revaccination. This was also the case for most of the high-dose vaccinated wild boar, except for one of them which succumbed after revaccination. Although this fatality was related to hierarchical fights between animals, we consider that further studies are required for clarification. Considering these new results and the current epidemiological situation of ASF in wild boar, this vaccine prototype is a promising tool for the control of the disease in these wild populations, although further studies are needed.

Anterograde transneuronal tracing and genetic control with engineered yellow fever vaccine YFV-17D.

Transneuronal viruses are powerful tools for tracing neuronal circuits or delivering genes to specific neurons in the brain. While there are multiple retrograde viruses, few anterograde viruses are available. Further, available anterograde viruses often have limitations such as retrograde transport, high neuronal toxicity, or weak signals. We developed an anterograde viral system based on a live attenuated vaccine of yellow fever – YFV-17D. Replication-deficient or packaging-deficient mutants of YFV-17D can be reconstituted in the brain, leading to efficient synapse-specific and anterograde-only transneuronal spreading, which can be controlled to achieve either monosynaptic or polysynaptic tracing. Moreover, inducible transient replication of YFV-17D mutant is sufficient to induce permanent transneuronal genetic modifications without causing neuronal toxicity. The engineered YFV-17D systems can be used to express fluorescent markers, sensors or effectors in downstream neurons, thus providing versatile tools for mapping and functionally controlling neuronal circuits.