Vaccine Delivery Strategies Research Articles

Expression of a leptospiral leucine-rich repeat protein using a food-grade vector in Lactobacillus plantarum, as a strategy for vaccine delivery.

In this study, a first food-grade mucosal vaccine against leptospirosis was developed without the use of antibiotic resistance gene. This expression system is based on a food-grade host/vector system of Lactobacillus plantarum and a new vaccine candidate antigen, a leucine-rich repeat (LRR) protein of Leptospira borgpetersenii. The LRR of interest from serovar Sejroe is encoded by two overlapping genes and these genes were fused together by site-directed mutagenesis. The mutant gene thus obtained could be successfully expressed in this system as was shown by western blot analysis and liquid chromatography-mass spectrometry (LC-MS/MS) analysis. In addition, this analysis showed that the mutant LRR protein fused to a homologous signal peptide of L. plantarum could be exported to the cell surface as a result of the native LPXAG motif of the heterologous LRR protein, which presumably is responsible for anchoring the protein to the cell wall of L. plantarum. This new strategy could be an essential tool for further studies of leptospirosis mucosal vaccine delivery.

Programmatic Preparations and challenges for OCV introduction in India

Cholera mainly affects the marginalized with inequitable access to care, potable water and improved sanitation. An estimated 411 million people in India are at risk from cholera, with 675,188 cases and 20,256 deaths occurring annually. Given the global elimination plan for cholera by 2030, a multi-stakeholder strategy is required. The National Technical Advisory Group on Immunization (NTAGI) Working Group on Cholera met in 2016 to review the evidence for cholera burden in India and successful oral cholera vaccine (OCV) implementation in other countries. Based on NTAGI’s recommendations, the Ministry of Health and Family Welfare will implement cholera control measures and decide on OCV’s addition to India’s Universal Immunization Programme (UIP). Key steps for OCV introduction will include choosing the vaccine formulation, developing vaccine delivery strategy, ensuring sufficient resources, engaging OCV manufacturers to ensure a sustainable supply, and developing a post-introduction evaluation strategy.

Maternal immunization in Malawi: A mixed methods study of community perceptions, programmatic considerations, and recommendations for future planning

BackgroundSafe, effective vaccines are given to pregnant women to protect their infants and/or themselves against certain infectious agents; however, apart from tetanus vaccination, maternal immunization in low- and middle-income countries (LMICs) remains low. Tetanus toxoid vaccine is integrated into antenatal care services in Malawi with high coverage and provides an opportunity to identify factors that facilitate successful immunization delivery to pregnant women in LMICs. MethodsPATH and the University of Malawi’s Centre for Social Research conducted a mixed-methods study in 2015 to document community perceptions of maternal immunization, using tetanus vaccine as an example, and to identify factors perceived to be important to successfully introducing other maternal vaccines, such as influenza vaccine, in Malawi. We conducted 18 focus group discussions with pregnant and recently pregnant women and their family members and 76 semi-structured interviews with pregnant and recently pregnant women, community leaders, health workers, public health program managers, non-governmental partners, and policy makers. ResultsWe identified factors perceived to support the introduction of new maternal vaccines, including strong maternal vaccine acceptance in the community, an existing strategy for maternal tetanus vaccine delivery, and positive health workers’ views about the introduction of additional maternal vaccines. Potential challenges to adoption and acceptance included identifying and tracking the target population and monitoring adverse events, and the need to ensure operational capacity of the health system to support the introduction and wide-scale use of an additional vaccine. For influenza vaccine specifically, additional challenges included limited awareness of influenza disease and its low prioritization among health needs. ConclusionsLessons from the successful delivery of maternal tetanus immunization in Malawi may be informative for similar countries considering new vaccines for pregnant women or striving to optimize the delivery of those currently provided.

Cell-penetrating Peptides: Efficient Vectors for Vaccine Delivery.

Subunit vaccines are composed of pathogen fragments that, on their own, are generally poorly immunogenic. Therefore, the incorporation of an immunostimulating agent, e.g. adjuvant, into vaccine formulation is required. However, there are only a limited number of licenced adjuvants and their im-munostimulating ability is often limited, while their toxicity can be substantial. To overcome these prob-lems, a variety of vaccine delivery systems have been proposed. Most of them are designed to improve the stability of antigen in vivo and its delivery into immune cells. Cell-penetrating peptides (CPPs) are especially attractive component of antigen delivery systems as they have been widely used to enhance drug transport into the cells. Fusing or co-delivery of antigen with CPPs can enhance antigen uptake, pro-cessing and presentation by antigen presenting cells (APCs), which are the fundamental steps in initiating an immune response. This review describes the different mechanisms of CPP intercellular uptake and various CPP-based vaccine delivery strategies.

Organization and implementation of an oral cholera vaccination campaign in an endemic urban setting in Dhaka, Bangladesh

ABSTRACTBangladesh has historically been cholera endemic, with seasonal cholera outbreaks occurring each year. In collaboration with the government of Bangladesh, the Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) initiated operational research to test strategies to reach the high-risk urban population with an affordable oral cholera vaccine (OCV) “ShancholTM” and examine its effectiveness in reducing diarrhea due to cholera. Here we report a sub-analysis focusing on the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. We described how the vaccination program was planned, prepared and implemented using different strategies to deliver oral cholera vaccine to a high-risk urban population in Dhaka, Bangladesh based on administrative data and observations made during the program. The objective of this study is to evaluate the organization, implementation and effectiveness of different oral cholera vaccine delivery strategies in the endemic urban setting in Bangladesh. OCV administration by trained local volunteers through outreach sites and mop-up activities yielded high coverage of 82% and 72% of 172,754 targeted individuals for the first and second dose respectively, using national Expanded Program on Immunization (EPI) campaign mechanisms without disrupting routine immunization activities. The cost of delivery was low. Safety and cold chain requirements were adequately managed. The adopted strategies were technically and programmatically feasible. Current evidence on implementation strategies in different settings together with available OCV stockpiles should encourage at-risk countries to use OCV along with other preventive and control measures.

Seroprevelence of rubella among children suspected of having measles in Gadarif Hospital, Eastern Sudan.

While generally mild in children, rubella infection during pregnancy can lead to miscarriage, foetal death or congenital rubella syndrome. Rubella vaccination is not yet available as a part of routine immunisation in Sudan, and the burden of infection is unknown. Using the clinical case definition adopted by the World Health Organisation, a total of 123 children suspected of having of measles were enrolled in this study during January-December 2017 in Gadarif Hospital, Eastern Sudan. Those cases whose sera were negative for measles IgM antibodies were tested for rubella IgM antibody. A confirmed rubella case was a person who tested positive for rubella IgM. Sera were analysed for IgM specific antibodies against measles virus and rubella virus using enzyme-linked immunosorbent assay. Among the total 123 children suspected to have measles, 92 (74.8%) children were positive for measles IgM antibodies. Of the 31 children who had measles IgM antibodies negative, 20 (16.3%) children were seropositive for rubella IgM antibodies. Implementation of a surveillance system will provide the improved estimates of rubella virus and estimated the burden of congenital rubella syndrome. Such information is necessary and it is an important step for future policy decisions for vaccine delivery strategies.

Developing a seasonal influenza vaccine recommendation in Kenya: Process and challenges faced by the National Immunization Technical Advisory Group (NITAG)

BackgroundIn 2014 the Kenya National Immunization Technical Advisory Group (KENITAG) was asked by the Ministry of Health to provide an evidence-based recommendation on whether the seasonal influenza vaccine should be introduced into the national immunization program (NIP). MethodsWe reviewed KENITAG manuals, reports and meeting minutes generated between June 2014 and June 2016 in order to describe the process KENITAG used in arriving at that recommendation and the challenges encountered. ResultsKENITAG developed a recommendation framework to identify critical, important and non-critical data elements that would guide deliberations on the subject. Literature searches were conducted in several databases and the quality of scientific articles obtained was assessed using the Critical Appraisal Skills Programme tool. There were significant gaps in knowledge on the national burden of influenza disease among key risk groups, i.e., pregnant women, individuals with co-morbidities, the elderly and health care workers. Insufficient funding and limited work force hindered KENITAG activities.In 2016 KENITAG recommended introduction of the annual seasonal influenza vaccine among children 6 to 23 months of age. However, the recommendation was contingent on implementation of a pilot study to address gaps in local data on the socio-economic impact of influenza vaccination programs, strategies for vaccine delivery, and the impact of the vaccination program on the healthcare workforce and existing immunization program. KENITAG did not recommend the influenza vaccine for any other risk group due to lack of local burden of disease data. ConclusionLocal data are a critical element in NITAG deliberations, however, where local data and in particular burden of disease data are lacking, there is need to adopt scientifically acceptable methods of utilizing findings from other countries to inform local decisions in a manner that is valid and acceptable to decision makers.

Clinical epidemiology of infectious disease among patients with chronic kidney disease

Infectious disease is recognized as an important complication among patients with end-stage renal disease, contributing to excess morbidity and health care costs. However, recent epidemiological studies have revealed that even mild to moderate stages of chronic kidney disease (CKD) substantially increase risk of infection. Regarding underlying mechanisms, evidence suggests various aspects of altered immune response in patients with CKD including impaired function of T cells, B cells and neutrophil. Multiple conditions surrounding CKD, such as older age, diabetes, and cardiovascular disease are important contributors in the increased susceptibility to infection in this population. In addition, several mechanisms impairing immune function have been hypothesized including accumulated uremic toxins, increased oxidative stress, endothelial dysfunction, low-grade inflammation, and mineral and bone disorders. In terms of prevention strategies, influenza and pneumococcal vaccines are most feasible and important. Nevertheless, the extent of vaccine utilization in CKD has not been well documented. In addition, antibody response to vaccination may be reduced in CKD patients, and thus a vaccine delivery strategy (e.g., dose and frequency) may need to be optimized among patients with CKD. Through this review, we demonstrate that infection is a major but underrecognized complication of CKD. As CKD is recognized as a serious public health issue, dedicated research is needed to better characterize the burden of infectious disease associated with CKD, understand the pathophysiology of infection in patients with CKD, and develop effective strategies to prevent infection and its sequela in this high risk population.

The viral approach to breast cancer immunotherapy.

Despite years of intensive research, breast cancer remains the leading cause of death in women worldwide. New technologies including oncolytic virus therapies, virus, and phage display are among the most powerful and advanced methods that have emerged in recent years with potential applications in cancer prevention and treatment. Oncolytic virus therapy is an interesting strategy for cancer treatment. Presently, a number of viruses from different virus families are under laboratory and clinical investigation as oncolytic therapeutics. Oncolytic viruses (OVs) have been shown to be able to induce and initiate a systemic antitumor immune response. The possibility of application of a multimodal therapy using a combination of the OV therapy with immune checkpoint inhibitors and cancer antigen vaccination holds a great promise in the future of cancer immunotherapy. Display of immunologic peptides on bacterial viruses (bacteriophages) is also increasingly being considered as a new and strong cancer vaccine delivery strategy. In phage display immunotherapy, a peptide or protein antigen is presented by genetic fusions to the phage coat proteins, and the phage construct formulation acts as a protective or preventive vaccine against cancer. In our laboratory, we have recently tested a few peptides (E75, AE37, and GP2) derived from HER2/neu proto-oncogene as vaccine delivery modalities for the treatment of TUBO breast cancer xenograft tumors of BALB/c mice. Here, in this paper, we discuss the latest advancements in the applications of OVs and bacterial viruses display systems as new and advanced modalities in cancer immune therapeutics.

Oral Delivery of a DNA Vaccine Expressing the PrM and E Genes: A Promising Vaccine Strategy against Flavivirus in Ducks

A flavivirus, named duck tembusu virus (DTMUV), emerged in China in 2010. This virus has caused great economic losses in the poultry industry in China and may pose a threat to public health. As a safe, efficient and convenient vaccine development strategy, DNA-based vaccines have become a popular approach for both human and veterinary applications. Attenuated bacteria have been widely used as vehicles to deliver heterologous antigens to the immune system. Thus, an efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-SME) based on envelope proteins (prM and E) of DTMUV and attenuated Salmonella typhimurium aroA- strain SL7207 was developed and evaluated in this study. The prM and E antigen proteins were successfully expressed from the vaccine SL7207 (pVAX1-SME) both in vitro and in vivo. High titers of the specific antibody against the DTMUV-E protein and the neutralizing antibody against the DTMUV virus were both detected after vaccination with SL7207 (pVAX1-SME). Ducks orally vaccinated with the SL7207 (pVAX-SME) vaccine were efficiently protected from lethal DTMUV infection in this study. Taken together, we demonstrated that prM and E proteins of DTMUV possess strong immunogenicity against the DTMUV infection. Moreover, an oral delivery of the DNA vaccine SL7207 (pVAX1-SME) utilizing Salmonella SL7207 was an efficient way to protect the ducks against DTMUV infection and provides an economic and fast vaccine delivery strategy for a large-scale clinical use.

Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the immunogenicity of neoantigen cancer vaccines

Cancer vaccines targeting patient-specific tumor neoantigens have recently emerged as a promising component of the rapidly expanding immunotherapeutic armamentarium. However, neoantigenic peptides typically elicit weak CD8+ T cell responses, and so there is a need for universally applicable vaccine delivery strategies to enhance the immunogenicity of these peptides. Ideally, such vaccines could also be rapidly fabricated using chemically synthesized peptide antigens customized to an individual patient. Here, we describe a strategy for simple and rapid packaging of peptide antigens into pH-responsive nanoparticles with endosomal escape activity. Electrostatically-stabilized polyplex nanoparticles (nanoplexes) can be assembled instantaneously by mixing decalysine-modified antigenic peptides and poly(propylacrylic acid) (pPAA), a polyanion with pH-dependent, membrane destabilizing activity. These nanoplexes increase and prolong antigen uptake and presentation on MHC-I (major histocompatibility complex class I) molecules expressed by dendritic cells, resulting in enhanced activation of CD8+ T cells. Using an intranasal immunization route, nanoplex vaccines inhibit formation of lung metastases in a murine melanoma model. Additionally, nanoplex vaccines strongly synergize with the adjuvant α-galactosylceramide (α-GalCer) in stimulating robust CD8+ T cell responses, significantly increasing survival time in mice with established melanoma tumors. Collectively, these findings demonstrate that peptide/pPAA nanoplexes offer a facile and versatile platform for enhancing CD8+ T cell responses to peptide antigens, with potential to complement ongoing advancements in the development of neoantigen-targeted cancer vaccines.

Neoantigen Vaccine Delivery for Personalized Anticancer Immunotherapy.

Cancer neoantigens derived from random somatic mutations in tumor tissue represent an attractive type of targets for the cancer immunotherapies including cancer vaccine. Vaccination against the tumor-specific neoantigens minimizes the potential induction of central and peripheral tolerance as well as the risk of autoimmunity. Neoantigen-based cancer vaccines have recently showed marked therapeutic potential in both preclinical and early-phase clinical studies. However, significant challenges remain in the effective and faithful identification of immunogenic neoepitopes and the efficient and safe delivery of the subunit vaccine components for eliciting potent and robust anticancer T cell responses. In this mini review, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines focusing on various vaccine delivery strategies for targeting and modulating antigen-presenting cells. We discuss current delivery approaches, including direct injection, ex vivo-pulsed dendritic cell vaccination, and biomaterial-assisted vaccination for enhancing the efficiency of neoantigen vaccines and present a perspective on future directions.

Implementation of maternal influenza immunization in El Salvador: Experiences and lessons learned from a mixed-methods study

IntroductionThe World Health Organization (WHO) recommends that countries prioritize pregnant women for influenza vaccination, yet few low- or middle-income countries (LMICs) have implemented maternal influenza immunization programs. To inform vaccine decision-making and operational planning in LMICs, there is a need to document and share experiences from countries that provide seasonal influenza vaccine to pregnant women, particularly those with high coverage, like El Salvador. MethodsIn 2015 and 2016, PATH and country researchers conducted a mixed-methods study to document the experience and lessons learned from maternal influenza immunization delivery and acceptance in El Salvador as part of a collaborative effort between WHO and PATH. Researchers conducted focus group discussions, semi-structured interviews, antenatal clinic exit interviews, and key informant interviews with 326 participants from two municipalities in each of the country’s three regions. Respondents included pregnant and recently pregnant women, family members, community leaders, health personnel, public health managers and partners, and policymakers. ResultsFactors perceived as positively influencing maternal influenza immunization delivery and acceptance in El Salvador include the use of multiple vaccine delivery strategies, targeted education and community engagement efforts, and a high degree of trust between the community and health care providers. Influenza vaccine acceptance by pregnant women is high and has improved over time, largely attributed to education targeting health care advisors. Perceived challenges to pregnant women receiving health care and vaccination include the need for permission to attend services and limited access to health services in insecure areas related to the presence of criminal gang activity. ConclusionsWe identified approaches and barriers perceived to affect maternal influenza vaccine delivery in El Salvador. This information will be useful to public health decision-makers and implementers in El Salvador and other countries considering introduction of new maternal vaccines or striving to increase coverage of vaccines currently provided.

Uptake of three doses of HPV vaccine by primary school girls in Eldoret, Kenya; a prospective cohort study in a malaria endemic setting

BackgroundAll women are potentially at risk of developing cervical cancer at some point in their life, yet it is avoidable cause of death among women in Sub- Saharan Africa with a world incidence of 530,000 every year. It is the 4th commonest cancer affecting women worldwide with over 260,000 deaths reported in 2012. Low resource settings account for over 75% of the global cervical cancer burden. Uptake of HPV vaccination is limited in the developing world. WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in developed countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines, therefore three doses may still be necessary. The aim of this study was to identify barriers and facilitators associated with uptake of HPV vaccine.MethodsA cross-sectional survey was conducted at Eldoret, Kenya involving 3000 girls aged 9 to 14 years from 40 schools. Parents/guardians gave consent through a questionnaire.ResultsOf all 3083 the school girls 93.8% had received childhood vaccines and 63.8% had a second HPV dose, and 39.1% had a third dose. Administration of second dose and HPV knowledge were both strong predictors of completion of the third dose. Distance to the hospital was a statistically significant risk factor for non-completion (P: 0.01).ConclusionsDistance to vaccination centers requires a more innovative vaccine-delivery strategy and education of parents/guardians on cervical screening to increase attainment of the HPV vaccination.

Oral Vaccination with a DNA Vaccine Encoding Capsid Protein of Duck Tembusu Virus Induces Protection Immunity.

The emergence of duck tembusu virus (DTMUV), a new member of the Flavivirus genus, has caused great economical loss in the poultry industry in China. Since the outbreak and spread of DTMUV is hard to control in a clinical setting, an efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-C) based on the capsid protein of DTMUV was developed and evaluated in this study. The antigen capsid protein was expressed from the DNA vaccine SL7207 (pVAX1-C), both in vitro and in vivo. The humoral and cellular immune responses in vivo were observed after oral immunization with the SL7207 (pVAX1-C) DNA vaccine. High titers of the specific antibody against the capsid protein and the neutralizing antibody against the DTMUV virus were both detected after inoculation. The ducks were efficiently protected from lethal DTMUV exposure by the SL7207 (pVAX1-C) vaccine in this experiment. Taken together, we demonstrated that the capsid protein of DTMUV possesses a strong immunogenicity against the DTMUV infection. Moreover, an oral delivery of the DNA vaccine SL7207 (pVAX1-C) utilizing Salmonella SL7207 was an efficient way to protect the ducks against DTMUV infection and provides an economic and fast vaccine delivery strategy for a large scale clinical use.

Immunogenicity and antitumor activity of the superlytic λF7 phage nanoparticles displaying a HER2/neu-derived peptide AE37 in a tumor model of BALB/c mice

Phage display technique has been increasingly researched for vaccine design and delivery strategies in recent years. In this study, the AE37 (Ii-Key/HER-2/neu 776–790) peptide derived from HER2 (human epidermal growth factor receptor protein) was used as a fused peptide to the lambda phage (λF7) coat protein gpD, and the phage nanoparticles were used to induce antitumor immunogenicity in a TUBO model of breast cancer in mice. Mice were immunized with the AE37 peptide displaying phage, λF7 (gpD::AE37) every 2-week intervals over 6-weeks, then the generated immune responses were evaluated. An induction of CTL immune response by the λF7 (gpD::AE37) construct compared to the control λF7 and buffer groups was observed in vitro. Moreover, in the in vivo studies, the vaccine candidate showed promising prophylactic and therapeutic effects against the HER2 overexpressing cancer in BALB/c mice.

Prevalence of Rubella Antibodies Among Children in the Democratic Republic of the Congo.

While generally mild in children, rubella infection in early pregnancy can lead to miscarriage, fetal death or congenital rubella syndrome. Rubella vaccination is not yet available as a part of routine immunization in the Democratic Republic of the Congo (DRC), and the burden of infection is unknown. In collaboration with the 2013-2014 DRC Demographic and Health Survey, a serosurvey was carried out to assess population immunity to vaccine-preventable diseases. Dry blood spot samples collected from children 6-59 months of age were processed using the Dynex Technologies Multiplier FLEX chemiluminescent immunoassay platform (Dynex Technologies, Chantilly, VA). Among the 7195 6- to 59-month-old children, 33% were positive and <1% indeterminate for rubella antibodies in weighted analyses. Seroprevalence was positively associated with age of the child and province, with seropositivity highest in Bandundu (53%) and lowest in Kasai-Oriental (20%). In multivariate analyses, serologic evidence of infection was associated with age of the mother and child, socioeconomic status and geographic location. Rubella infection is prevalent among children in the DRC, and while most seroconversion occurs in young children, a significant proportion of children remain at risk and may enter reproductive age susceptible to rubella infection. While not currently in place, implementation of a surveillance program will provide improved estimates of both rubella virus circulation and the burden of congenital rubella syndrome. Such information will play an important role in future policy decisions, vaccine delivery strategies and may provide a basis upon which the effectiveness of rubella antigen introduction may be assessed.

Nasal delivery of H5N1 avian influenza vaccine formulated with GenJet™ or in vivo-jetPEI® induces enhanced serological, cellular and protective immune responses

Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI®, and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model. Detailed analyses of adaptive immune responses revealed that both formulations induced mixed TH1/TH2 antigen-specific CD4 T-cell responses, antigen-specific cytotoxic CD8 T-cell and memory B-cell responses. Our findings suggest that cationic polymers merit future development as potential adjuvants for mucosal delivery of poorly immunogenic vaccines.

Innovative vaccine delivery strategies in response to a cholera outbreak in the challenging context of Lake Chilwa. A rapid qualitative assessment

A reactive campaign using two doses of Shanchol Oral Cholera Vaccine (OCV) was implemented in 2016 in the Lake Chilwa Region (Malawi) targeting fish dependent communities. Three strategies for the second vaccine dose delivery (including delivery by a community leader and self-administration) were used to facilitate vaccine access.This assessment collected vaccine perceptions and opinions about the OCV campaign of 313 study participants, including: fishermen, fish traders, farmers, community leaders, and one health and one NGO officer. Socio-demographic surveys were conducted, In Depth Interviews and Focus Group Discussions were conducted before and during the campaign.Some fishermen perceived the traditional delivery strategy as reliable but less practical. Delivery by traditional leaders was acceptable for some participants while others worried about traditional leaders not being trained to deliver vaccines or beneficiaries taking doses on their own. A slight majority of beneficiaries considered the self-administration strategy practical while some beneficiaries worried about storing vials outside of the cold chain or losing vials. During the campaign, a majority of participants preferred receiving oral vaccines instead of injections given ease of intake and lack of pain. OCV was perceived as efficacious and safe. However, a lack of information on how sero-protection may be delayed and the degree of sero-protection led to loss of trust in vaccine potency among some participants who witnessed cholera cases among vaccinated individuals.OCV campaign implementation requires accompanying communication on protective levels, less than 100% vaccine efficacy, delays in onset of sero-protection, and out of cold chain storage.

Comparison of school based and supplemental vaccination strategies in the delivery of vaccines to 5-19 year olds in Africa - a systematic review.

Some vaccine preventable diseases (VPDs) still remain a public health burden in many African countries. The occurrence of VPDs in all age groups has led to the realization of the need to extend routine immunisation services to school age children, adolescents and adults. Supplemental immunisation activities (SIAs) and school based vaccinations (SBVs) are common strategies used to complement the expanded programme on immunisation (EPI). This review aimed to assess the effectiveness of SIAs compared to SBVs in the administration of vaccines to 5-19 year olds in Africa. Systematic review methods were used to address our study aim. Several electronic databases were searched up to March 30, 2017 for primary studies investigating the delivery of vaccines via SIAs or SBVs to 5-19 year olds. This search was complemented by browsing reference lists of potential studies obtained from search outputs. Outcomes considered for inclusion were: vaccination coverage, costs of the strategy or its effect on routine immunisation services. Out of the 4938 studies identified, 31 studies met the review inclusion criteria. Both SIAs and SBVs showed high vaccination coverage. However, the SIAs reported higher coverage than SBVs: 91% (95% CI: 84%, 98%) versus 75% (95% CI: 67%, 83%). In most settings, SBVs were reported to be more expensive than SIAs. The SIAs were found to negatively affect routine immunisation services. Both SIAs and SBVs are routinely used to complement the EPI in the delivery of vaccines in Africa. In settings where school enrolment is suboptimal, as is the case in many African countries, our results show SIAs may be more effective in reaching school age children and adolescents than SBVs. Our results re-iterate the importance of evaluating systematic evidence to best inform African authorities on the optimal vaccine delivery strategies targeting school age children and adolescents.