A thermostable presentation of the live,attenuated peste des petits ruminants vaccine in use in Africa and Asia

The research objective was to develop a thermostable vaccine against peste des petits ruminants (PPR), a morbilliviral disease of small ruminants targeted for eradication that is a major constraint on the livelihoods of the rural poor throughout much of Africa and Asia. Although existing PPR vaccines provide life-long immunity, they require continuous refrigeration. This limits their utility in developing countries. Methods for the lyophilization of a related morbillivirus, rinderpest (RP), resulted in vaccine that could be used in the field for up to 30 days without refrigeration which was a major contribution to the global eradication of RP completed in 2011. The present research applied the rinderpest lyophilization method to the attenuated Nigeria 75/1 PPR vaccine strain, and measured thermostability in accelerated stability tests (AST) at 37 °C. The shelf-life of the vaccine was determined as the time a vial retained the minimum dose required as a 25-dose presentation at the specified temperature. A lactalbumin hydrolysate and sucrose (LS) stabilizer was compared to stabilizers based on trehalose. PPR vaccine produced using the Xerovac drying method was compared to vaccine produced using the rinderpest lyophilization method in AST. LS vaccine was evaluated in AST at 37, 45 and 56 °C and an Arrhenius plot was constructed for estimation of stability at temperatures not tested. Vaccines produced using LS and the rinderpest method of lyophilization were the most stable. The shelf-life of the Xerovac preparation was 22.2 days at 37 °C. The three LS vaccine batches had shelf-lives at 37 °C of 177.6, 105.0 and 148.9 days, respectively, at 37 °C. At 56 °C, the shelf-life was 13.7 days. The projected half-life at 25 °C was 1.3 years. This is sufficient thermostability for use without a cold chain for up to 30 days which will greatly facilitate the delivery of vaccination in the global eradication of PPR.     

Scalable culture systems using different cell lines for the production of Peste des Petits ruminants vaccine

Peste des Petits ruminants (PPR) is considered as one of the major constraints to the productivity of small ruminants in Africa and Asian countries. Currently PPR control is done by vaccination with an attenuated PPR strain (Nigeria 75/1) produced in monolayers of Vero cells grown in roller bottles or static flasks. This work focuses on the production of a PPR vaccine strain using stirred conditions as an advanced option for process scale-up. Non-porous microcarriers (Cytodex-1) were used to support Vero cell growth in suspension cultures. The use of Ex-Cell medium could improve cell specific productivities obtained with standard serum containing medium, independently of the type of system used, i.e. static as well as suspension stirred cultures. As an alternative, several cell lines adapted to grow as single cells in suspension (CHO-K1, BHK-21A and 293) and another anchorage-dependent (MRC-5) were evaluated in their capacity to produce a PPR vaccine. BHK-21A and 293 cells grown as single-cell suspension in serum free medium were both suited to produce PPR vaccine with productivities similar to Vero cells, namely 10(6)TCID(50)/mL. However, for the 293 cells, these results were only obtained 2-3 days later. CHO-K1 and MRC-5 cells have shown not to be suitable to adequately produce this virus. These results provide further insights into the feasibility of applying microcarrier cell culture technology to produce PPR vaccine in Vero cells as well as in the alternative use of single-cell suspension cultures of BHK-21A, significantly simplifying the existing production process.     

The detection of antibodies against peste des petits ruminants virus in cattle, sheep and goats and the possible implications to rinderpest control programmes.

Monoclonal antibody-based competitive ELISA (C-ELISA) have been used for the specific measurement of antibodies to both rinderpest and peste des petits ruminants (PPR) viruses in cattle, sheep and goats. Examination of serum samples from sheep and goats in Gambia, before and after vaccination with rinderpest vaccine, suggested that antibodies to PPR virus could prevent an immune response to the rinderpest vaccine. Cattle sera from Nigeria and Ghana showed a high prevalence of antibody against PPR virus which may explain the difficulty experienced in some countries in achieving high post-vaccination immunity levels against rinderpest. Because antibodies against PPR virus are both cross-neutralizing and cross-protective against rinderpest virus further vaccination in the presence of antibodies against PPR virus may be a waste of national resources. This paper presents serological evidence for the transmission of PPR virus from sheep and goats to cattle and highlights the need to include PPR serology in the sero-monitoring programme to give a better indication of national herd immunity.     

An alternate delivery system improves vaccine performance against foot-and-mouth disease virus (FMDV)

Foot-and-mouth disease virus (FMDV) causes vesicular disease of cloven-hoofed animals with severe agricultural and economic implications. One of the most highly infectious and contagious livestock pathogens known, the disease spreads rapidly in naïve populations making it critical to have rapidly acting vaccines. Needle inoculation of killed virus vaccine is an efficient method of swiftly vaccinating large numbers of animals, either in eradication efforts or in outbreak situations in disease free countries, although, to be efficient, this requires utilizing the same needle with multiple animals. Here we present studies using a needle free system for vaccination with killed virus vaccine, FMDV strain O1 Manisa, as a rapid and consistent delivery platform. Cattle were vaccinated using a commercially available vaccine formulation at the manufacturer's recommended dose as well as four and sixteen fold less antigen load per dose. Animals were challenged intradermalingually (IDL) with live, virulent virus, homologous strain O1 Manisa, at various times following vaccination. All non-vaccinated control cattle exhibited clinical disease, including fever, viremia and lesions, specifically vesicle formation. Cattle vaccinated with the 1/16× and 1/4× doses using the needle free device were protected when challenged at both 7 and 28 days after vaccination. These data suggest that effective protection against disease can be achieved with 1/16 of the recommended vaccine dose when delivered using the needle free, intradermal delivery system, indicating the current vaccine stockpile that can be extended by many fold using this system.     

Modelling the relative benefits of using the measles vaccine outside cold chain for outbreak response

IntroductionRapid outbreak response vaccination is a strategy for measles control and elimination. Measles vaccines must be stored and transported within a specified temperature range, but this can present significant challenges when targeting remote populations. Measles vaccine licensure for delivery outside cold chain (OCC) could provide more vaccine transport/storage space without ice packs, and a solution to shorten response times. However, due to vaccine safety and wastage considerations, the OCC strategy will require other operational changes, potentially including the use of 1-dose (monodose) instead of 10-dose vials, requiring larger transport/storage equipment currently achieved with 10-dose vials. These trade-offs require quantitative comparisons of vaccine delivery options to evaluate their relative benefits.MethodsWe developed a modelling framework combining elements of the vaccine supply chain - cold chain, vial, team, and transport equipment types - with a measles transmission dynamics model to compare vaccine delivery options. We compared 10 strategies resulting from combinations of the vaccine supply elements and grouped into three main classes: OCC, partial cold chain (PCC), and full cold chain (FCC). For each strategy, we explored a campaign with 20 teams sequentially targeting 5 locations with 100,000 individuals each. We characterised the time needed to freeze ice packs and complete the campaign (campaign duration), vaccination coverage, and cases averted, assuming a fixed pre-deployment delay before campaign commencement. We performed sensitivity analyses of the pre-deployment delay, population sizes, and two team allocation schemes.ResultsThe OCC, PCC, and FCC strategies achieve campaign durations of 50, 51, and 52 days, respectively. Nine of the ten strategies can achieve a vaccination coverage of 80%, and OCC averts the most cases.DiscussionThe OCC strategy, therefore, presents improved operational and epidemiological outcomes relative to current practice and the other options considered.     

Delivery cost of human papillomavirus vaccination of young adolescent girls in Peru,Uganda and Viet Nam

Objective

To estimate the incremental delivery cost of human papillomavirus (HPV) vaccination of young adolescent girls in Peru, Uganda and Viet Nam.

Methods

Data were collected from a sample of facilities that participated in five demonstration projects for HPV vaccine delivery: school-based delivery was used in Peru, Uganda and Viet Nam; health-centre-based delivery was also used in Viet Nam; and integrated delivery, which involved existing health services, was also used in Uganda. Microcosting methods were used to guide data collection on the use of resources (i.e. staff, supplies and equipment) and data were obtained from government, demonstration project and health centre administrative records. Delivery costs were expressed in 2009 United States dollars (US$). Exclusively project-related expenses and the cost of the vaccine were excluded.

Findings

The economic delivery cost per vaccine dose ranged from US$ 1.44 for integrated outreach in Uganda to US$ 3.88 for school-based delivery in Peru. In Viet Nam, the lowest cost per dose was US$ 1.92 for health-centre-based delivery. Cost profiles revealed that, in general, the largest contributing factors were project start-up costs and recurrent personnel costs. The delivery cost of HPV vaccine was higher than published costs for traditional vaccines recommended by the Expanded Programme on Immunization (EPI).

Conclusion

The cost of delivering HPV vaccine to young adolescent girls in Peru, Uganda and Viet Nam was higher than that for vaccines currently in the EPI schedule. The cost per vaccine dose was lower when delivery was integrated into existing health services.     

Uganda--rehabilitation, or redefinition of health services?

Uganda had one of the best health care delivery systems in Africa. The decade of misrule by Amin saw a collapse of the country and an exodus of doctors and other professions. The 1979 liberation war and subsequent political instability and insecurity further aggravated the poor health services then available. When political stability was temporarily restored in December 1980 the cash crop export sector took priority over social services and the health budget declined to only 3.5% compared to a former level of 7.5% of government budget. Emergencies in West Nile, Karamoja and the Luwero triangle continued to plague rehabilitation efforts upto 1985. Alternate strategies for improving health are proposed including female education, increased budget allocations, food and nutrition policy and health information. Uganda's prospect for rebuilding the health services has begun with immunization, control of diarrhoeal diseases, nutrition surveillance in Karamoja and an essential drugs programme, but the success of these is dependent upon political stability and improvement in overall security.     

Comparative effectiveness of mandates and financial policies targeting COVID-19 vaccine hesitancy: A randomized,controlled survey experiment

Experts debate whether COVID-19 vaccine mandates or financial incentives will reduce, rather than increase, interest in vaccination. Among 3,698 unvaccinated U.S. residents, we conducted a randomized, controlled survey-embedded experiment to estimate the absolute and relative psychological effects of vaccine policies specifying: mandates by employers or airlines, bars, and restaurants; lotteries for $1 million, $200,000, or $100,000; guaranteed cash for $1000, $200, or $100; and $1,000 as either a tax credit or penalty. Vaccine intention —the study outcome— predicts uptake and provides insight into the psychological mechanism that is most proximal to behavior (i.e., vaccination). Compared to controls, those who learned about the $1,000 cash reward policy were 17.1 (±5.3)% more likely to want vaccination. Employer mandates are more promising than other mandate policies (8.6 [+/- 7.4]% vs. 1.4 [+/- 6.0]%). The full results suggest that neither mandates nor financial incentives are likely to have counterproductive psychological effects. These policies are not mutually exclusive and, if implemented well, they may increase vaccine uptake.     

Reducing resistance to polio immunisation with free health camps and Bluetooth messaging: An update from Kaduna,Northern, Nigeria

Since 1997, the Global Polio Eradication Initiative has sponsored regular door-to-door polio immunisation campaigns in northern Nigeria. On 30 July 2015, the country was finally declared poliofree, a hard won success. At various times, polio eradication has been threatened by rumours and community tensions. For example, in 2003, local Imams, traditional leaders and politicians declared a polio campaign boycott, due to the concerns about the safety of the polio vaccine. Although the campaigns resumed in 2004, many parents continued to refuse vaccination because of the persistence of rumours of vaccine contamination, and anger about the poor state of health services for conditions other than polio. To address this, UNICEF and Nigerian Government partners piloted two interventions: (1) mobile ‘health camps’ to provide ambulatory care for conditions other than polio and (2) an audiovisual clip about vaccine safety and other health issues, shareable on multimedia mobile phones via Bluetooth pairing. The mobile phone survey found that Bluetooth compatible messages could rapidly spread behavioural health messages in low-literacy communities. The health camps roughly doubled polio vaccine uptake in the urban ward where it was piloted. This suggests that polio eradication would have been accelerated by improving primary health care services.     

Uptake of Mpox vaccination among transgender people and gay,bisexual and other men who have sex with men among sexually-transmitted infection clinic clients in Vancouver,British Columbia

ObjectivesAs the primary public health strategy for controlling the 2022 Mpox outbreak, it is critical to evaluate the impact of Mpox vaccination campaigns for transgender people and gay, bisexual and other men who have sex with men (T/GBM). We measured vaccine uptake and associated factors among T/GBM clients of an urban STI clinic in British Columbia (BC).MethodsWe conducted a cross-sectional online survey between August 8–22, 2022 of clients who had attended the STI clinic, 5–7 weeks following the first-dose Mpox vaccination campaign in BC. We drew on a systematic review of factors associated with vaccine uptake to develop survey questions, and measured vaccine uptake among vaccine-eligible T/GBM.ResultsOverall, 51% of T/GBM had received the first dose of the vaccine. The sample (331 participants) was majority White and university educated, identified as a man and gay, 10% had trans experience, and 68% met eligibility criteria for vaccination. Among vaccine-eligible participants identifying as T/GBM, 66% had been vaccinated; being unvaccinated was more common among participants identifying as bisexual or heteroflexible/mostly straight, and who spent less time with other T/GBM. Eligible yet unvaccinated participants had lower perceived susceptibility, and reported fewer cues to action (e.g., fewer saw information promoting the vaccine), and increased constraints to vaccine access; vaccine barriers related to accessing clinics and privacy were common. The majority (85%) of those eligible and unvaccinated at time of survey were willing to receive the vaccine.ConclusionIn this sample of STI clinic clients, vaccine uptake among eligible T/GBM was high in the initial weeks following a Mpox vaccination campaign. However, uptake was patterned on social gradients with lower uptake among T/GBM who may be less effectively engaged by available promotion channels. We recommend early, intentional and diverse engagement of T/GBM populations in Mpox and other targeted vaccination programs.     

Health care professional communication about STI vaccines with adolescents and parents

Vaccination of adolescents against sexually transmitted infections (STIs) is an important prevention strategy that may reduce the global burden of disease. The World Health Organization, Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, and other national health agencies recommend the use of existing STI vaccines, and many countries have incorporated them into their routine vaccination schedule. Despite this, however, data indicate that STI vaccine uptake is suboptimal for a variety of reasons. Health care professionals (HCP) have been shown to have a strong beneficial effect on STI vaccine uptake, yet studies demonstrate that many HCPs fail to discuss or recommend them to adolescent patients. This review article focuses on HCP communication about STI vaccines with adolescents and their parents. It describes STI vaccine message content and delivery as well as the context in which HCPs formulate their messaging approach. It also examines other contextual factors that may shape communication about STI vaccines. Studies from many countries indicate that HCPs often possess misinformation about adolescents, including their sexual risk behaviors, as well as STIs, vaccine safety and efficacy, and STI vaccination recommendations. They also have misconceptions of parental barriers to STI vaccination. These may impact STI vaccine communication and have a negative influence on STI vaccine uptake. These findings highlight the critical need for improved HCP education related to adolescent health, sexuality, and STI vaccination. This may be particularly important in settings without an existing infrastructure or expertise in caring for this unique patient population.     

An impact assessment of the use of aerial logistics to improve access to vaccines in the Western-North Region of Ghana

BackgroundPrevention of infectious diseases among children is crucial to improve child health and survival. However, many countries in Sub-Saharan Africa struggle to achieve vaccination targets due to supply chain challenges, which lead to vaccine shortages, stockouts, and increased costs. We evaluated the effects of aerial logistics (centralized storage and delivery by drones) on vaccine stock, stockouts, vaccination coverage and vaccine preventable outcomes in the Western North Region of Ghana.MethodsThe study combined retrospective quasi-experimental and cross-sectional designs to evaluate supply chain, programmatic, and clinical outcomes. Surveys to health providers were used to collect information from a random sample of 156 facilities, and secondary data on vaccination coverage and clinical outcomes was analyzed at the district level for the years 2017–2021.ResultsFacilities served by aerial logistics reported significant reductions in the duration of vaccine stockouts (30 %, p-value < 0.05), as well as in the frequency of missed opportunities for vaccination (44 %, p-value < 0.05). Being served by aerial logistics was associated with increased satisfaction with access to vaccines. Significant differences in vaccination coverage were found for most vaccines, in a range between 13.1 and 37.5 percentage points in vaccination coverage for served districts. Infectious diarrhea cases in children between 5 and 9 years old were reduced by 41.6 % (p-value < 0.05).ConclusionEnd-to-end aerial logistics appears as an effective tool to improve the performance of the supply chain for vaccines. The strategy potentially increases the resilience of the health system and contributes to increased vaccination coverage and higher levels of satisfaction among providers in the Western North Region of Ghana.     

Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns,intentions and maternal vaccination with subsequent childhood vaccine uptake

IntroductionMaternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood.MethodsWomen attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR).ResultsBetween October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value < 0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake.ConclusionFirst time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy for all mothers in pregnancy and post delivery, particularly first-time mothers.     

HPV vaccination acceptance and perceptions related to fertility and population control in the Gambia: An anthropological analysis

This qualitative study using in-depth interviews and focus group discussions is the first to investigate HPV vaccination in The Gambia; it provides an in-depth analysis of uptake, knowledge, and perceptions of HPV vaccination as well as trust in Ministry of Health vaccination advice. Despite high uptake rates, knowledge of HPV vaccination was low, and the most prominent concern was that the vaccine could cause infertility or is a form of population control. Holistic approaches to addressing HPV vaccine concerns relating to fertility that consider socio-political contexts, including colonial histories, could lead to more positive vaccine perceptions, empowered decisions and to increasing vaccine uptake rates in The Gambia and elsewhere.     

A goat poxvirus-vectored peste-des-petits-ruminants vaccine induces long-lasting neutralization antibody to high levels in goats and sheep

Recombinant capripoxvirus (CPV) is a promising candidate differentiating infected from vaccinated animals (DIVA) vaccine against peste-des-petits-ruminants (PPR). In order for recombinant CPV to be successfully used in the field, there should exist dependable indicators for quality control of vaccine products, surveillance and vaccination evaluation. Viral neutralization antibody (VNA) is correlated to protection against PPR and is a technically feasible indicator for this purpose. The immunogenicity of this vectored vaccine in goats and sheep, however, has not been fully evaluated. In this study, we generated two recombinant CPV viruses, rCPV-PPRVH and rCPV-PPRVF, that express PPR virus (PPRV) glycoproteins H and F, respectively. Vaccination studies with different dosages of recombinant viruses showed that rCPV-PPRVH was a more potent inducer of PPRV VNA than rCPV-PPRVF. One dose of rCPV-PPRVH was enough to seroconvert 80% of immunized sheep. A second dose induced significantly higher PPRV VNA titers. There was no significant difference in PPRV VNA responses between goats and sheep. Subcutaneous inoculation also induced a significant PPRV VNA response. PPRV VNA could be detected for over 6 months in more than 80% of vaccinated goats and sheep. Boost vaccination at 6-month intervals induced significant re-boost efficacy of PPRV VNA in goats and sheep. More over, two doses of rCPV-PPRVH could completely overcome the interference caused by pre-existing immunity to the CPV vaccine backbone in animals. Vaccination with rCPV-PPRVH also protected goats from virulent CPV challenge. Our results demonstrate that VNA can serve as a dependent indicator for effective vaccination and immune protection of animals in the field. The recombinant CPV vaccine used in our studies could be a practical and useful candidate DIVA vaccine in countries where PPR newly emerges or where stamp-out plans are yet to be implemented.     

Influence of Sociocultural Practices on Food and Nutrition Security in Karamoja Subregion of Uganda

The study determined the influence of sociocultural practices on food and nutrition security of children and women in Karamoja subregion, located in northeastern Uganda. Sixteen focus group discussions were conducted among 133 participants. Data were analyzed using qualitative content analysis. Findings indicate that cultural norms, myths, and taboos restrict consumption of animal-sourced foods and some green vegetables by women. Sociocultural practices promoted prelacteal feeding, affecting the implementation of World Health Organization’s recommendations for exclusive breast feeding. In conclusion, sociocultural practices influence food and nutrition security, exposing women and children to the risk of malnutrition and associated consequences.     

Intranasal and sublingual delivery of inactivated polio vaccine

Polio is on the brink of eradication. Improved inactivated polio vaccines (IPV) are needed towards complete eradication and for the use in the period thereafter. Vaccination via mucosal surfaces has important potential advantages over intramuscular injection using conventional needle and syringe, the currently used delivery method for IPV. One of them is the ability to induce both serum and mucosal immune responses: the latter may provide protection at the port of virus entry.The current study evaluated the possibilities of polio vaccination via mucosal surfaces using IPV based on attenuated Sabin strains. Mice received three immunizations with trivalent sIPV via intramuscular injection, or via the intranasal or sublingual route. The need of an adjuvant for the mucosal routes was investigated as well, by testing sIPV in combination with the mucosal adjuvant cholera toxin.Both intranasal and sublingual sIPV immunization induced systemic polio-specific serum IgG in mice that were functional as measured by poliovirus neutralization. Intranasal administration of sIPV plus adjuvant induced significant higher systemic poliovirus type 3 neutralizing antibody titers than sIPV delivered via the intramuscular route. Moreover, mucosal sIPV delivery elicited polio-specific IgA titers at different mucosal sites (IgA in saliva, fecal extracts and intestinal tissue) and IgA-producing B-cells in the spleen, where conventional intramuscular vaccination was unable to do so. However, it is likely that a mucosal adjuvant is required for sublingual vaccination. Further research on polio vaccination via sublingual mucosal route should include the search for safe and effective adjuvants, and the development of novel oral dosage forms that improve antigen uptake by oral mucosa, thereby increasing vaccine immunogenicity. This study indicates that both the intranasal and sublingual routes might be valuable approaches for use in routine vaccination or outbreak control in the period after complete OPV cessation and post-polio eradication.     

Preventable Disease Practices Among a Lower SES,Multicultural, Nonurban,U.S. Community: The Roles of Vaccination Efficacy and Personal Constraints

In spite of knowledge that early vaccination against contagious diseases such as swine flu reduces morbidity and contains contagion, rates of vaccination in the most recent three annual disease cycles were lower than anticipated. Some previous research suggests that lower socioeconomic status, mixed-racial population composition, and a nonurban environment may all contribute to lower vaccination rates. This study adopts the health belief model to create two composite indexes—vaccine efficacy and personal constraints—to analyze the role of each in predicting vaccination behavior/intention and to explore the role of each on behavior/intention in terms of information sources. Findings indicate that vaccine efficacy significantly predicts vaccination behavior and intention to receive the vaccine and that personal constraints do not significantly predict either. Social media and a notification from a school or employer were the most important information sources for persons who had received the vaccine, while signage in a pharmacy or grocery store and information from a school or employer were the most important motivators for behavioral intentions. Vaccination efficacy was perceived most highly by persons for whom physicians are their most important information source. Finally, satisfaction with public health care services did not predict the location where individuals would seek the flu vaccine—convenience seemed more important, as grocery and drug stores were the most cited locations.     

Improved influenza vaccination in the skin using vaccine coated microneedles

Easy and effective vaccination methods could reduce mortality rates and morbidity due to vaccine-preventable influenza infections. In this study, we examined the use of microneedle patches to increase patient coverage through possible self-administration and enhance vaccine immunogenicity by targeted delivery to skin. We carried out a detailed study of protective immune responses after a single influenza vaccination to the skin of mice with a novel microneedle patch designed to facilitate simple and reliable vaccine delivery. Skin vaccination with inactivated virus-coated microneedles provided superior protection against lethal challenge compared to intramuscular injection as evidenced by effective virus clearance in lungs. Detailed immunologic analysis suggests that induction of virus neutralizing antibodies as well as enhanced anamnestic humoral and cellular responses contributed to improved protection by microneedle vaccination to the skin. These findings suggest that vaccination in the skin using a microneedle patch can improve protective immunity, and simplify delivery of influenza and possibly other vaccines.     

Funding gap for immunization across 94 low- and middle-income countries

Novel vaccine development and production has given rise to a growing number of vaccines that can prevent disease and save lives. In order to realize these health benefits, it is essential to ensure adequate immunization financing to enable equitable access to vaccines for people in all communities. This analysis estimates the full immunization program costs, projected available financing, and resulting funding gap for 94 low- and middle-income countries over five years (2016–2020). Vaccine program financing by country governments, Gavi, and other development partners was forecasted for vaccine, supply chain, and service delivery, based on an analysis of comprehensive multi-year plans together with a series of scenario and sensitivity analyses.Findings indicate that delivery of full vaccination programs across 94 countries would result in a total funding gap of $7.6 billion (95% uncertainty range: $4.6–$11.8 billion) over 2016–2020, with the bulk (98%) of the resources required for routine immunization programs. More than half (65%) of the resources to meet this funding gap are required for service delivery at $5.0 billion ($2.7–$8.4 billion) with an additional $1.1 billion ($0.9–$2.7 billion) needed for vaccines and $1.5 billion ($1.1–$2.0 billion) for supply chain. When viewed as a percentage of total projected costs, the funding gap represents 66% of projected supply chain costs, 30% of service delivery costs, and 9% of vaccine costs. On average, this funding gap corresponds to 0.2% of general government expenditures and 2.3% of government health expenditures.These results suggest greater need for country and donor resource mobilization and funding allocation for immunizations. Both service delivery and supply chain are important areas for further resource mobilization. Further research on the impact of advances in service delivery technology and reductions in vaccine prices beyond this decade would be important for efficient investment decisions for immunization.