Cost-effectiveness analysis measuring the total costs against the health benefits of three different rotavirus vaccines for Mexico.

Rotavirus (RV) infection causes acute rotavirus gastroenteritis (RVGE) in infants. Safe and effective RV vaccines are available, of which Mexico has included one in its national immunization program (NIP) since 2007. Health outcome gains, expressed in quality-adjusted life years (QALYs), and cost improvements are important additional factors for the selection of a NIP vaccine. These two factors were analyzed here for Mexico over one year implementing three RV vaccines: 2-dose Rotarix (HRV), versus 3-dose RotaTeq (HBRV), and 3-dose Rotasiil (BRV-PV), presented in a 1-dose or 2-dose vial). HRV would annually result in discounted QALY gains of 263 extra years compared with the other vaccines by averting an extra 24,022 homecare cases, 10,779 medical visits, 392 hospitalizations, and 12 deaths. From a payer's perspective and compared with HRV, BRV-PV 2-dose vial and BRV-PV 1-dose vial would annually result in $13,548,179 and $4,633,957 net savings, respectively, while HBRV would result in $3,403,309 extra costs. The societal perspective may also show savings compared with HRV for BRV-PV 2-dose vial of $4,875,860, while BRV-PV 1-dose vial and HBRV may show extra costs of $4,038,363 and $12,075,629 respectively. HRV and HBRV were both approved in Mexico, with HRV requiring less investment than HBRV with higher QALY gains and cost savings. The HRV vaccine produced those higher health gains due to its earlier protection and greater coverage achieved after its schedule completion with two doses only, providing full protection at four months of age instead of longer periods for the other vaccines.

Rotavirus (RV) infection causes acute diarrhea in infants and can be life-threatening. Several safe and effective vaccines against RV and its complications exist. For many governments choosing vaccines for national immunization programs, total costs or savings and health gains are important factors in the selection process. We compared the costs and health benefits of three RV vaccines for Mexico: HRV, HBRV, and BRV-PV, that have different dosing schedules: two doses for HRV and three doses for HBRV and BRV-PV. HRV is currently part of the national immunization program in Mexico. HRV would result in more health benefits as it incurs fewer RV-related cases, medical visits, hospitalizations, and infant deaths than the other vaccines due to its early protection achieved after only two doses to complete its schedule. However, from a payer's perspective, the least expensive vaccine was BRV-PV, while HRV was less expensive than HBRV. From a societal perspective, also accounting for families' costs and loss in income due to an infant's RV disease, and the families' costs and loss in income when accompanying the infant to the vaccination center, the HRV vaccine was less expensive than HBRV and BRV-PV presented in a 1-dose vial, while more expensive than BRV-PV presented in a 2-dose vial. HRV and HBRV are both approved in Mexico, although HBRV requires a greater investment at lower health benefits than HRV, from both a payer's and a societal perspective. A 2-dose vaccination scheme is an important asset for the economic value of this vaccination program.

Production performance and economic analysis of broiler chickens after vaccination with a live attenuated vaccine against avian coccidiosis.

The objective of this study was to evaluate the effectiveness of live attenuated commercial vaccine LIVACOX® T against avian coccidiosis upon parasite exposure through its correlation with productive and economic performance, clinical observation, and oocyst excretion of broiler chickens. For this purpose, 420 1-day-old Cobb chicks were divided into five groups of 84 birds: (G1) unvaccinated and unchallenged control; (G2) vaccinated on day 0; (G3) challenged on day 1; (G4) vaccinated on day 0 and challenged on day 14; and (G5) challenged on day 14. For 28 days, the clinical signs of infection, weight and feed conversion of the birds, and excretion of oocysts in the feces were evaluated. Macroscopic analysis of intestinal lesions in birds was also performed. After vaccination in G2, G3, and G4 as well as after challenge in G3, G4, and G5, there was an increase in oocyst excretion. In the analysis of weight gain, the difference in final weight between groups G3 and G4 is - 105.74 g per bird. Therefore, if we multiply this value by the average number of birds slaughtered per day in a medium/large slaughterhouse (250,000), we have 26,435 kg of chicken meat per day of slaughter, representing 581,570 kg of monthly losses (22 days of slaughter/month), or approximately R$3,489,420.00 (US$872,355.00), considering the commercial value at R$6.00/kg (US$ 1.5/kg). Thus, the productive and economic impact of coccidiosis in broiler chickens is evident, and the importance of vaccination to prevent the occurrence of the disease and reduce subsequent loss is highlighted.

Cost-Effectiveness and Health Impacts of Different Influenza Vaccination Strategies for Children in China.

INTRODUCTION: Authors aimed to evaluate the economic and health impacts of three influenza vaccines available in China, including trivalent inactivated vaccine, quadrivalent inactivated vaccine, and live attenuated influenza vaccine, for children aged six months to 18 years. METHODS: Two decision-analytic models were developed to simulate four vaccination strategies. Outcomes included total costs from a societal perspective in 2021, quality-adjusted life-year loss, numbers of outpatient and inpatient cases, and deaths avoided using each strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the uncertainty of model inputs. RESULTS: For children aged six months to three years, trivalent inactivated vaccine saved $48 million and avoided a loss of 17,637 quality-adjusted life-years compared with no vaccination. For children aged 3-18 years, quadrivalent inactivated vaccine was cost-effective compared with trivalent inactivated vaccine, with an incremental cost-effectiveness ratio of $32,948.5/quality-adjusted life-year (willingness-to-pay threshold=$37,653/quality-adjusted life-year), which was sensitive to the RR of vaccine effectiveness of quadrivalent inactivated vaccine versus of trivalent inactivated vaccine. When compared with quadrivalent inactivated vaccine, live attenuated influenza vaccine was $1.28 billion more costly but gained an additional 13,560 quality-adjusted life-years; its incremental cost-effectiveness ratio was $123,983.8/quality-adjusted life-year. Live attenuated influenza vaccine would be cost-effective if its vaccine effectiveness was >0.79. Probabilistic sensitivity analysis revealed that quadrivalent inactivated vaccine, trivalent inactivated vaccine, live attenuated influenza vaccine, and no vaccination were cost-effective in 55.94%, 33.09%, 10.97%, and 0% of 10,000 Monte Carlo simulations. CONCLUSIONS: Trivalent inactivated vaccine was cost-effective compared with no vaccination in children aged six months to 18 years. Of the three vaccination strategies for children aged 3-18 months, quadrivalent inactivated vaccine appears to be the most cost-effective.

Assessment of attenuation of varicella-zoster virus vaccines based on genomic comparison.

Live attenuated varicella-zoster virus (VZV) vaccines are used to prevent chickenpox and shingles. Single nucleotide polymorphisms (SNPs) that occur during the attenuation of parental strains are critical indicators of vaccine safety. To assess the attenuation of commercial VZV vaccines, genetic variants were comprehensively examined through high-throughput sequencing of viral DNA isolated from four VZV vaccines (Barycela, VarilRix, VariVax, and SKY Varicella). Whole-genome comparison of the four vaccines with the wild-type strain (Dumas) revealed that the sequences are highly conserved on a genome-wide scale. Among the 196 common variants across the four vaccines, 195 were already present in the genome of the parental strain (pOka), indicating that the variants occurred during the generation of the parental strain from the Dumas strain. Compared to the pOka genome, the vaccines exhibited distinct variant frequencies on a genome-wide and within an attenuation-related open reading frame. In particular, attenuation-associated 42 SNPs showed that Barycela, VarilRix, VariVax, and SKY Varicella are in ascending order regarding similarity with pOka-like genotypes, which in turn, might provide genomic evidence for the levels of attenuation. Finally, the phylogenetic network analysis demonstrated that genetic distances from the parental strain correlated with the attenuation levels of the vaccines.

Safety assessment of compliant, highly invasive, lipid A-altered, O-antigen-defected Salmonella strains as prospective vaccine delivery systems.

In the present study, two prospective Salmonella delivery strains, JOL2782 and JOL2837, were developed by gene deletions of lon and cpxR, which are related to cellular adhesion and intracellular survival. Additionally, sifA deletion was introduced for JOL2782, which confers immune susceptibility and improves antigen delivery. Similarly, the rfaL deletion and lpxE substitution for pagL were accomplished in JOL2837 to reduce virulence and endotoxicity. Thus, enhanced adhesion and invasion and reduced intracellular survival were attained. Furthermore, aspartic acid auxotrophic (asd) was deleted to impose Darwinian selection on retention of the foreign antigen-expressing plasmid. Both delivery strains induced sufficient cytokine expression, but the level was significantly lower than that of the wild-type strain; the lowest cytokine expression was induced by the JOL2837 strain, indicating reduced endotoxicity. In parallel, IgG production was significantly enhanced by both delivery strains. Thus, the innate and adaptive immunogenicity of the strains was ensured. The environmental safety of these strains was ascertained through faecal dissemination assays. The nonpathogenicity of these strains to the host was confirmed by body weight monitoring, survival assays, and morphological and histological assessments of the vital organs. The in vitro assay in murine and human cell lines and in vivo safety assessments in mice suggest that these novel strains possess safety, invasiveness, and immunogenicity, making them ideal delivery strains. Overall, the results clearly showed that strain JOL2782 with sifA deletion had higher invasiveness, demonstrating superior vaccine deliverability, while JOL2837 with lpxE substitution for pagL and rfaL deletion had outstanding safety potential with drastically abridged endotoxicity.

Effect of different vaccine strategies for the control of Japanese encephalitis in mainland China from 1961 to 2020: A quantitative analysis.

BACKGROUND: We aimed to quantify the impact of each vaccine strategy (including the P3-inactivated vaccine strategy [1968-1987], the SA 14-14-2 live-attenuated vaccine strategy [1988-2007], and the Expanded Program on Immunization [EPI, 2008-2020]) on the incidence of Japanese encephalitis (JE) in regions with different economic development levels. METHODS: The JE incidence in mainland China from 1961 to 2020 was summarized by year, then modeled and analyzed using an interrupted time series analysis. RESULTS: After the P3-inactivated vaccine was used, the JE incidence in Eastern China, Central China, Western China and Northeast China in 1968 decreased by 39.80 % (IRR = 0.602, P < 0.001), 7.80 % (IRR = 0.922, P < 0.001), 10.80 % (IRR = 0.892, P < 0.001) and 31.90 % (IRR = 0.681, P < 0.001); the slope/trend of the JE incidence from 1968 to 1987 decreased by 30.80 % (IRR = 0.692, P < 0.001), 29.30 % (IRR = 0.707, P < 0.001), 33.00 % (IRR = 0.670, P < 0.001) and 41.20 % (IRR = 0.588, P < 0.001). After the SA 14-14-2 live-attenuated vaccine was used, the JE incidence in Eastern China and Northeast China in 1988 decreased by 2.60 % (IRR = 0.974, P = 0.009) and 14.70 % (IRR = 0.853, P < 0.001); the slope/trend of the JE incidence in Eastern China and Central China from 1988 to 2007 decreased by 4.60 % (IRR = 0.954, P < 0.001) and 4.70 % (IRR = 0.953, P < 0.001). After the EPI was implemented, the JE incidence in Eastern China, Central China and Western China in 2008 decreased by 10.50 % (IRR = 0.895, P = 0.013), 18.00 % (IRR = 0.820, P < 0.001) and 24.20 % (IRR = 0.758, P < 0.001), the slope/trend of the JE incidence in Eastern China from 2008 to 2020 decreased by 17.80 % (IRR = 0.822, P < 0.001). CONCLUSIONS: Each vaccine strategy has different effects on the JE incidence in regions with different economic development. Additionally, some economically underdeveloped regions have gradually become the main areas of the JE outbreak. Therefore, mainland China should provide economic assistance to areas with low economic development and improve JE vaccination plans in the future to control the epidemic of JE.

Recombinant vesicular stomatitis vaccine against Nipah virus has a favorable safety profile: Model for assessment of live vaccines with neurotropic potential.

Nipah virus (NiV) disease is a bat-borne zoonosis responsible for outbreaks with high lethality and is a priority for vaccine development. With funding from the Coalition of Epidemic Preparedness Innovations (CEPI), we are developing a chimeric vaccine (PHV02) composed of recombinant vesicular stomatitis virus (VSV) expressing the envelope glycoproteins of both Ebola virus (EBOV) and NiV. The EBOV glycoprotein (GP) mediates fusion and viral entry and the NiV attachment glycoprotein (G) is a ligand for cell receptors, and stimulates neutralizing antibody, the putative mediator of protection against NiV. PHV02 is identical in construction to the registered Ebola vaccine (Ervebo) with the addition of the NiV G gene. NiV ephrin B2 and B3 receptors are expressed on neural cells and the wild-type NiV is neurotropic and causes encephalitis in affected patients. It was therefore important to assess whether the NiV G alters tropism of the rVSV vector and serves as a virulence factor. PHV02 was fully attenuated in adult hamsters inoculated by the intramuscular (IM) route, whereas parental wild-type VSV was 100% lethal. Two rodent models (mice, hamsters) were infected by the intracerebral (IC) route with graded doses of PHV02. Comparator active controls in various experiments included rVSV-EBOV (representative of Ebola vaccine) and yellow fever (YF) 17DD commercial vaccine. These studies showed PHV02 to be more neurovirulent than both rVSV-EBOV and YF 17DD in infant animals. PHV02 was lethal for adult hamsters inoculated IC but not for adult mice. In contrast YF 17DD retained virulence for adult mice inoculated IC but was not virulent for adult hamsters. Because of the inconsistency of neurovirulence patterns in the rodent models, a monkey neurovirulence test (MNVT) was performed, using YF 17DD as the active comparator because it has a well-established profile of quantifiable microscopic changes in brain centers and a known reporting rate of neurotropic adverse events in humans. In the MNVT PHV02 was significantly less neurovirulent than the YF 17DD vaccine reference control, indicating that the vaccine will have an acceptable safety profile for humans. The findings are important because they illustrate the complexities of phenotypic assessment of novel viral vectors with tissue tropisms determined by transgenic proteins, and because it is unprecedented to use a heterologous comparator virus (YF vaccine) in a regulatory-enabling study. This approach may have value in future studies of other novel viral vectors.

Comparison of virus detection, productivity, and economic performance between lots of growing pigs vaccinated with two doses or one dose of PRRS MLV vaccine, under field conditions.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes a significant economic impact on swine production. It has been demonstrated that PRRS modified-live virus (MLV) vaccination of pigs, with one full dose, significantly reduces clinical consequences of wild-type PRRSV infection compared to non-vaccinates. However, there is limited information about the effect that two doses of PRRSV MLV vaccine have on the performance of growing pigs, compared to vaccination with a single dose. This study was conducted with the objectives to compare (a) the wild-type PRRSV detection in oral fluids over time, (b) key closeout productivity indicators, and (c) economic performance between lots of growing pigs vaccinated with two doses of Ingelvac PRRS® MLV vaccine and lots vaccinated with a single dose of the same vaccine. This randomized field trial included 15 lots of growing pigs from PRRSV positive-unstable sow farms and 66 lots from PRRSV positive-stable sow farms, according to the American association of swine veterinarians' terminology. All pig lots received the first vaccination either around processing or weaning age. Lots allocated in the two doses group received the second vaccination three to four weeks after the first vaccination. The pig lots were monitored for PRRSV detection over time. Six oral fluids samples were collected in three weeks intervals and were tested for wild-type PRRSV-2 RNA by RT-qPCR and open reading frame 5 (ORF)- 5 sequencing. Regression models were used to compare wild-type PRRSV detection dynamics on oral fluids samples and to compare key closeout performance indicators between one dose group and two doses group. Additionally, a benefit-cost ratio analysis compared economic performance between one dose group and two doses group. The proportion of wild-type PRRSV detection on oral fluids samples and the log counts of viral RNA per ml of oral fluids from the two doses group was lower than the one dose group on lots originated from PRRSV positive-stable sow farms, with a risk ratio of 1.24 and a rate ratio of 1.17, respectively. The two doses group had a significantly lower mortality rate than the one dose group, with a rate ratio of 1.21. The effect size increased on lots originated from PRRSV positive-unstable sow farms, and on lots with higher frequency and diversity of wild-type PRRSV detection during the growth phase. No differences in growth performance were detected between two doses group and one dose group. The second MLV vaccination dose had a benefit-cost ratio of 1.83. For lots originated from PRRSV positive-unstable farms, the benefit-cost ratio was 4.45, and for lots originated from PRRSV positive-stable farms, the benefit-cost ratio was 0.45. Under study conditions, vaccinating growing pig lots with two doses of PRRS MLV vaccine was a useful strategy to immunize growing pigs against PRRSV, lowering the wild-type PRRSV detection, lowering mortality rate, and increasing profitability, compared to lots of growing pigs that received a single dose of the same vaccine.

Cost-Effectiveness Analysis of Herpes Zoster Vaccination in 50- to 85-Year-Old Immunocompetent Belgian Cohorts: A Comparison between No Vaccination, the Adjuvanted Subunit Vaccine, and Live-Attenuated Vaccine.

BACKGROUND: A new adjuvanted subunit vaccine (HZ/su), with higher vaccine efficacy than live-attenuated vaccine (ZVL), has been licensed in Europe since March 2018. Therefore, Belgian decision-makers might need to re-assess their recommendations for vaccination against herpes zoster (HZ). METHODS: We conducted a cost-effectiveness analysis, using a Markov decision tree, of vaccinating 50- to 85-year-old immunocompetent Belgian cohorts with no vaccination, HZ/su, ZVL, and ZVL with booster after 10 years. Due to the uncertainty in vaccine waning of HZ/su vaccine beyond 4 years, we used a logarithmic and 1-minus-exponential function to model respectively a long and short duration of protection. We used a lifetime time horizon and implemented the health care payer perspective throughout the analysis. RESULTS: HZ/su had the greatest impact in avoiding health and economic burden. However, it would never become cost-effective at a willingness-to-pay threshold of €40,000 per quality-adjusted life year (QALY) gained at its market price set by the manufacturer in the USA. Depending on the waning function assumed for HZ/su, the price per dose needs to drop 60% or 83% such that vaccination with HZ/su, assuming respectively a long or short duration of protection, would become cost-effective in 50- and 80-year-old individuals. At €40,000 per QALY gained, ZVL or ZVL with booster was never found cost-effective compared with HZ/su, even if only administration cost was considered. CONCLUSION: HZ/su is cost-effective in the 50-year-old age cohort at the unofficial Belgian threshold of €40,000 per QALY gained, if its price drops to €55.40 per dose. This result is, however, very sensitive to the assumed duration of protection of the vaccine, and the assumed severity and QALY loss associated with HZ and post-herpetic neuralgia (PHN).

Promising Technologies in the Field of Helminth Vaccines.

Helminths contribute a larger global burden of disease than both malaria and tuberculosis. These eukaryotes have caused human infections since before our earliest recorded history (i.e.: earlier than 1200 B.C. for Schistosoma spp.). Despite the prevalence and importance of these infections, helminths are considered a neglected tropical disease for which there are no vaccines approved for human use. Similar to other parasites, helminths are complex organisms which employ a plethora of features such as: complex life cycles, chronic infections, and antigenic mimicry to name a few, making them difficult to target by conventional vaccine strategies. With novel vaccine strategies such as viral vectors and genetic elements, numerous constructs are being defined for a wide range of helminth parasites; however, it has yet to be discussed which of these approaches may be the most effective. With human trials being conducted, and a pipeline of potential anti-helminthic antigens, greater understanding of helminth vaccine-induced immunity is necessary for the development of potent vaccine platforms and their optimal design. This review outlines the conventional and the most promising approaches in clinical and preclinical helminth vaccinology.

Description of changes of key performance indicators and PRRSV shedding over time in a naïve breeding herd following a PRRS MLV exposure.

Porcine reproductive and respiratory syndrome (PRRS) is an important economic swine disease. The usage of PRRS-modified live vaccines (MLV) is the predominant breeding herd immunologic solution used in the United States to minimize the economic losses associated with wild-type PRRS infection. Most of the current information on the effects of contemporary PRRS MLV vaccination on breeding herd performance under field conditions comes from herds with previous PRRS virus (PRRSV) exposure. Hence, there is little information on key performance indicators (KPI) changes after the exposure to a PRRS MLV in PRRSV-naïve breeding herds. The main objective of this longitudinal observational study was to describe selected KPI changes in a naïve breeding herd after PRRS MLV exposure. The secondary objective was to describe the pattern of detection of PRRSV RNA by the quantitative reverse transcriptase-polymerase chain reaction in processing fluid samples. There were transient increases for mummies during weeks 4-23 (+0.86%); increased pre-weaning mortality on weeks 3-5 (+3.76%); a decrease in live born on weeks 4-5 (-0.46) leading to a decreased pig weaned/litter on weeks 5-10 (-0.69) and increased repeated services on weeks 3-23 (+5.53%). Transient changes observed after PRRS MLV exposures did not move total pigs weaned to outside the control intervals. Starting on week 83 and for 53 consecutive weeks, there was no PRRSV detection in processing fluids, even though two whole-herd MLV exposures occurred within that period.

Implementation strategies for the first licensed dengue vaccine: A meeting report.

Dengue vaccination would enhance the control of dengue, one of the most frequent vector-borne viral diseases globally. CYD-TDV is the first dengue vaccine to be licensed, but global uptake has been hampered due to its use being limited to seropositive persons aged 9 years and above, and the need for a 3-dose schedule. The Partnership for Dengue Control (PDC) organized a meeting with key opinion leaders and stakeholders to deliberate on implementation strategies for the use of CYD-TDV. New data have emerged that support the shortening of the primary schedule from a 3 to 2 dose schedule, extending the age range below 9 to 6 years of age, and expanding the indication from endemic populations to also include travelers to endemic areas. Cost-effectiveness may improve with the modified 2-dose regimen and with multiple testing. Strategies to implement a dengue vaccination program have been developed, in particular school-based strategies. A range of delivery scenarios can then be considered, using various settings for each step of the intervention. However, several challenges remain, including communication about limiting the use of this vaccine to seropositive individuals only. Affordability will vary from country to country, as will government commitment and community acceptance. Well-tailored communication strategies that target key stakeholders are expected to make up a significant part of any future dengue vaccination program.

Assessment of microbiological correlates and immunostimulatory potential of electron beam inactivated metabolically active yet non culturable (MAyNC) Salmonella Typhimurium.

This study investigates the microbiological and immunological basis underlying the efficacy of electron beam-inactivated immune modulators. The underlying hypothesis is that exposure to eBeam-based ionization reactions inactivate microorganisms without modifying their antigenic properties and thereby creating immune modulators. The immunological correlates of protection induced by such eBeam based Salmonella Typhimurium (EBST) immune modulators in dendritic cell (DC) (in vitro) and mice (in vivo) models were assessed. The EBST stimulated innate pro inflammatory response (TNFα) and maturation (MHC-II, CD40, CD80 and CD86) of DC. Immuno-stimulatory potential of EBST was on par with both a commercial Salmonella vaccine, and live Salmonella cells. The EBST cells did not multiply under permissive in vitro and in vivo conditions. However, EBST cells remained metabolically active. EBST immunized mice developed Salmonella-specific CD4+ T-cells that produced the Th1 cytokine IFNγ at a level similar to that induced by the live attenuated vaccine (AroA- ST) formulation. The EBST retained stable immunogenic properties for several months at room temperature, 4°C, and -20°C as well as after lyophilization. Therefore, such eBeam-based immune modulators have potential as vaccine candidates since they offer the safety of a "killed" vaccine, while retaining the immunogenicity of an "attenuated" vaccine. The ability to store eBeam based immune modulators at room temperature without loss of potency is also noteworthy.

Developing a manufacturing process to deliver a cost effective and stable liquid human rotavirus vaccine.

Despite solid evidence of the success of rotavirus vaccines in saving children from fatal gastroenteritis, more than 82 million infants worldwide still lack access to a rotavirus vaccine. The main barriers to global rotavirus vaccine coverage include cost, manufacturing capacity and suboptimal efficacy in low- and lower-middle income countries. One vaccine candidate with the potential to address the latter is based on the novel, naturally attenuated RV3 strain of rotavirus, RV3-BB vaccine administered in a birth dose strategy had a vaccine efficacy against severe rotavirus gastroenteritis of 94% at 12 months of age in infants in Indonesia. To further develop this vaccine candidate, a well-documented and low-cost manufacturing process is required. A target fully loaded cost of goods (COGs) of ≤$3.50 per course of three doses was set based on predicted market requirements. COGs modelling was leveraged to develop a process using Vero cells in cell factories reaching high titers, reducing or replacing expensive reagents and shortening process time to maximise output. Stable candidate liquid formulations were developed allowing two-year storage at 2-8 °C. In addition, the formulation potentially renders needless the pretreatment of vaccinees with antacid to ensure adequate gastric acid neutralization for routine oral vaccination. As a result, the formulation allows small volume dosing and reduction of supply chain costs. A dose ranging study is currently underway in Malawi that will inform the final clinical dose required. At a clinical dose of ≤6.3 log10 FFU, the COGs target of ≤$3.50 per three dose course was met. At a clinical dose of 6.5 log10 FFU, the final manufacturing process resulted in a COGs that is substantially lower than the current average market price, 2.44 USD per dose. The manufacturing and formulation processes were transferred to BioFarma in Indonesia to enable future RV3-BB vaccine production.

Vaccine effectiveness of live attenuated and trivalent inactivated influenza vaccination in 2010/11 to 2015/16: the SIVE II record linkage study.

BACKGROUND: There is good evidence of vaccine effectiveness in healthy individuals but less robust evidence for vaccine effectiveness in the populations targeted for influenza vaccination. The live attenuated influenza vaccine (LAIV) has recently been recommended for children in the UK. The trivalent influenza vaccine (TIV) is recommended for all people aged ≥ 65 years and for those aged < 65 years who are at an increased risk of complications from influenza infection (e.g. people with asthma). OBJECTIVE: To examine the vaccine effectiveness of LAIV and TIV. DESIGN: Cohort study and test-negative designs to estimate vaccine effectiveness. A self-case series study to ascertain adverse events associated with vaccination. SETTING: A national linkage of patient-level general practice (GP) data from 230 Scottish GPs to the Scottish Immunisation & Recall Service, Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register. PARTICIPANTS: A total of 1,250,000 people. INTERVENTIONS: LAIV for 2- to 11-year-olds and TIV for older people (aged ≥ 65 years) and those aged < 65 years who are at risk of diseases, from 2010/11 to 2015/16. MAIN OUTCOME MEASURES: The main outcome measures include vaccine effectiveness against laboratory-confirmed influenza using real-time reverse-transcription polymerase chain reaction (RT-PCR), influenza-related morbidity and mortality, and adverse events associated with vaccination. RESULTS: Two-fifths (40%) of preschool-aged children and three-fifths (60%) of primary school-aged children registered in study practices were vaccinated. Uptake varied among groups [e.g. most affluent vs. most deprived in 2- to 4-year-olds, odds ratio 1.76, 95% confidence interval (CI) 1.70 to 1.82]. LAIV-adjusted vaccine effectiveness among children (aged 2-11 years) for preventing RT-PCR laboratory-confirmed influenza was 21% (95% CI -19% to 47%) in 2014/15 and 58% (95% CI 39% to 71%) in 2015/16. No significant adverse events were associated with LAIV. Among at-risk 18- to 64-year-olds, significant trivalent influenza vaccine effectiveness was found for four of the six seasons, with the highest vaccine effectiveness in 2010/11 (53%, 95% CI 21% to 72%). The seasons with non-significant vaccine effectiveness had low levels of circulating influenza virus (2011/12, 5%; 2013/14, 9%). Among those people aged ≥ 65 years, TIV effectiveness was positive in all six seasons, but in only one of the six seasons (2013/14) was significance achieved (57%, 95% CI 20% to 76%). CONCLUSIONS: The study found that LAIV was safe and effective in decreasing RT-PCR-confirmed influenza in children. TIV was safe and significantly effective in most seasons for 18- to 64-year-olds, with positive vaccine effectiveness in most seasons for those people aged ≥ 65 years (although this was significant in only one season). FUTURE WORK: The UK Joint Committee on Vaccination and Immunisation has recommended the use of adjuvanted injectable vaccine for those people aged ≥ 65 years from season 2018/19 onwards. A future study will be required to evaluate this vaccine. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88072400. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 67. See the NIHR Journals Library website for further project information.

In Scotland, a new type of influenza vaccine (live attenuated influenza vaccine), administered via the nose, was introduced in 2014/15 for all children aged between 2 and 11 years. It can be difficult to evaluate any changes in health as a result of new immunisation programmes, given that randomised controlled trials of vaccines are impractical and can also be seen as unethical. These changes are therefore typically not evaluated, making it difficult to inform future policy in this field. Observational studies can be used to assess the effects of health-care interventions without influencing the care that is provided or affecting the people who receive it. An evaluation (effectiveness and safety) of this change in the immunisation programme was conducted. The vaccine programme, an inactivated vaccine administered as an injection, for other groups for whom the evidence available is limited was also evaluated [i.e. for people aged ≥ 65 years and people aged < 65 years who have a medical condition (e.g. asthma) that puts them at risk of severe illness from influenza]. The findings support the view that the intranasal vaccine is effective and safe in preventing influenza in children. The injectable vaccine in people aged < 65 years who are more at risk of complications from flu was safe and effective. Lower effectiveness was found in people aged ≥ 65 years. Both the injectable vaccine and the intranasal vaccine have high levels of uptake in the population offered vaccination. When considering these results, the important limitation of bias in observational study designs should be noted [for instance, residual confounding, whereby it is not possible to measure a characteristic of those people receiving the vaccine (e.g. being healthier)], and this is accounted for in this analysis.

Assessment of A20 infectious laryngotracheitis vaccine take in meat chickens using swab and dust samples following mass vaccination in drinking water.

Infectious laryngotracheitis, caused by the alphaherpesvirus infectious laryngotracheitis virus (ILTV), is an important disease of chickens. Partial control of this disease in meat chickens is commonly achieved by mass vaccination with live virus in drinking water. There is a need for a practical test to evaluate vaccination outcomes. For the Serva ILTV vaccine, quantitative real-time PCR (qPCR) enumeration of ILTV genome copies (GC) in flock level dust samples collected at 7-8 days post vaccination (dpv) can be used to differentiate flocks with poor and better vaccine take. This study aimed to validate this approach for A20, another widely used ILT vaccine in Australia. In four meat chicken flocks vaccinated with A20 in water using two different water stabilization times (20 or 40 min), swabs from the trachea and choanal cleft and dust samples were collected at 0, 7, 14 and 21 dpv. ILTV GC detection in swabs and dust was highest at 7 dpv and at this time ILTV GC load in dust was strongly and positively associated with vaccine take in individual birds assessed by swab samples. Choanal cleft swabs provided significantly fewer ILTV positive results than paired tracheal swab samples but the level of ILTV GC detected was similar. Water stabilization time had only minor effects on vaccination response in favour of the shorter time. Location of dust collection had no effect on viral load measured in dust samples. Dust samples collected at 0 and 7 dpv can be used to assess the vaccination status of flocks.