Showing papers in "Human Vaccines & Immunotherapeutics in 2012"
TL;DR: The use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines, and advances will help to accelerate the development and testing of new mucosalvaccines against many human and animal diseases.
Abstract: Most pathogens enter the body through mucosal surfaces. Mucosal immunization, a non-invasive needle-free route, often stimulates a mucosal immune response that is both effective against mucosal and systemic pathogens. The development of mucosally administered heat-stable vaccines with long shelf life would therefore significantly enhance immunization programs in developing countries by avoiding the need for a cold chain or systemic injections. Currently, recombinant vaccine carriers are being used for antigen delivery. Engineering Bacillus subtilis for use as a non-invasive and heat stable antigen delivery system has proven successful. Bacterial spores protected by multiple layers of protein are known to be robust and resistant to desiccation. Stable constructs have been created by integration into the bacterial chromosome of immunogens. The spore coat has been used as a vehicle for heterologous antigen presentation and protective immunization. Sublingual (SL) and intranasal (IN) routes have recently received attention as delivery routes for therapeutic drugs and vaccines and recent attempts by several investigators, including our group, to develop vaccines that can be delivered intranasally and sublingually have met with a lot of success.
As discussed in this Review, the use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines. In our work, we evaluated the efficacy of SL and IN immunizations with B. subtilis engineered to express tetanus toxin fragment C (TTFC) in mice and piglets. These bacteria engineered to express heterologous antigen either on the spore surface or within the vegetative cell have been used for oral, IN and SL delivery of antigens. A Bacillus subtilis spore coat protein, CotC was used as a fusion partner to express the tetanus fragment C. B. subtilis spores known to be highly stable and safe are also easy to purify making this spore-based display system a potentially powerful approach for surface expression of antigens. These advances will help to accelerate the development and testing of new mucosal vaccines against many human and animal diseases.
345 citations
TL;DR: Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place.
Abstract: Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza...
333 citations
TL;DR: The long-term efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix®) up to 8.4 y after the first vaccine dose was reported, and the safety profile was clinically acceptable for both vaccine and control groups.
Abstract: Prophylactic human papillomavirus (HPV) vaccines are now available and vaccination programs are being widely implemented, targeting adolescent girls prior to sexual debut. Since the risk of HPV exposure persists throughout a woman’s sexual life, the duration of protection provided by vaccination is critical to the overall vaccine effectiveness. We report the long-term efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix®) up to 8.4 y after the first vaccine dose. In an initial placebo-controlled study performed in US, Canada and Brazil, women aged 15–25 y with normal cervical cytology, HPV-16/18 seronegative by ELISA, DNA-negative for 14 oncogenic HPV types by PCR, received either the HPV-16/18 vaccine or placebo (n = 1,113). Subjects were followed up to 6.4 y after the first dose (n = 776). We report an additional 2-y follow-up for women enrolled from the Brazilian centers from the initial study (n = 436). During the current follow-up study (HPV-023, NCT00518336), no new infec...
183 citations
TL;DR: The phages have been applicable to immunization therapies, which may lead to development of new tools used for treating autoimmune and cancer diseases and the recent advancements in therapeutic applications of phage display are presented.
Abstract: One of the most effective molecular diversity techniques is phage display This technology is based on a direct linkage between phage phenotype and its encapsulated genotype, which leads to present
174 citations
TL;DR: The herd immunity assessment in Catalonia, Spain, showed that the additional vaccination coverage required to establish herd immunity was 3–6% for measles, mump and varicella and 11% poliovirus type III in school children, youth and adults.
Abstract: The necessary herd immunity blocking the transmission of an infectious agent in the population is established when the prevalence of protected individuals is higher than a critical value, called the herd immunity threshold. The establishment of herd immunity in the population can be determined using the vaccination coverage and seroepidemiological surveys. The vaccination coverage associated with herd immunity (V(c)) can be determined from the herd immunity threshold and vaccine effectiveness. This method requires a vaccine-specific effectiveness evaluation, and it can be used only for the herd immunity assessment of vaccinated communities in which the infectious agent is not circulating. The prevalence of positive serological results associated with herd immunity can be determined from the herd immunity threshold, in terms of prevalence of antibodies (p(c)) and serological test performance. The herd immunity is established when the prevalence of antibodies is higher than pc. This method can be used to assess the establishment of herd immunity in different population groups, both when the infectious agent is circulating and when it is not possible to assess vaccine effectiveness. The herd immunity assessment in Catalonia, Spain, showed that the additional vaccination coverage required to establish herd immunity was 3-6% for measles, mump and varicella and 11% poliovirus type III in school children, 17-59% for diphtheria in youth and adults and 25-46% for persussis in school children, youth and adults.
118 citations
TL;DR: Findings suggest that IL-17A producing Th17 cells play an essential role in IsdB vaccine-mediated defense against invasive S. aureus infection in mice.
Abstract: We have previously shown that IsdB, a conserved protein expressed by Staphylococcus aureus, induces a robust antibody response which correlates with protection in a murine challenge model. Here we investigate the role of cellular immunity in IsdB mediated protection using lymphocyte deficient SCID mice. As opposed to WT CB-17 mice the CB-17 SCID mice were not protected against a lethal challenge of S. aureus after active and passive immunizations with IsdB. Adoptive transfer of in vitro isolated lymphocyte subsets revealed that reconstituting mice with IsdB specific CD3+ or CD4+ T-cells conferred antigen specific protection while CD8(+) T-cells, CD19(+) B-cells and plasma cells (CD138(high)B220(int)CD19(lo)) alone were not protective. A combination of CD3(+) T-cells plus CD19(+) B-cells conferred protection in CB-17 SCID mice, whereas bovine serum albumin (BSA) immune lymphocytes did not confer protection. Active immunization experiments indicated that IsdB immunized Jh mice (B-cell deficient) were protected against lethal challenge, while nude (T-cell deficient) mice were not. In vitro assays indicated that isolated IsdB specific splenocytes from immunized mice produced abundant IL-17A, much less IFN-γ and no detectable IL-4. IL-23 deficient mice were not protected from a lethal challenge by IsdB vaccination, pointing to a critical role for CD4(+) Th17 in IsdB-mediated vaccination. Neutralizing IL-17A, but not IL-22 in vivo significantly increased mortality in IsdB immunized mice; whereas, neutralizing IFN-γ did not alter IsdB-mediated protection. These findings suggest that IL-17A producing Th17 cells play an essential role in IsdB vaccine-mediated defense against invasive S. aureus infection in mice.
111 citations
TL;DR: The laboratory and clinical studies leading to prequalification of MenAfriVacTM are summarized and the vaccine was introduced at public health scale using a single 10 µg dose in individuals 1–29 y of age in Burkina Faso, Mali, and Niger in December 2010.
Abstract: Group A meningococcal disease has been an important public health problem in sub-Saharan Africa for over a century. Outbreaks occur there annually, and large epidemics occur at intervals ranging between 8 and 12 y. The Meningitis Vaccine Project was established in 2001 with funding from the Gates Foundation with the goal of developing, testing, licensing, and introducing an affordable group A meningococcal conjugate vaccine into Africa. From 2003 to 2009 a monovalent group A conjugate vaccine, MenAfriVacTM, was developed at the Serum Institute of India, Ltd through an innovative public/private partnership. Preclinical studies of the new conjugate vaccine were completed in 2004 and a Phase 1 study began in India in 2005. Phase 2/3 studies in African 1–29 y olds were completed in 2009 showing the new meningococcal A conjugate vaccine to be as safe as currently licensed meningococcal polysaccharide vaccines, but much more immunogenic. After Indian market authorization (December 2009) and WHO prequalification...
109 citations
TL;DR: Estimating the influenza burden is a useful aid to determining the best influenza vaccination strategy and preventive and clinical treatments for influenza epidemics and pandemics.
Abstract: Influenza epidemics and pandemics carry a heavy socioeconomic burden. Hospitalization and treatment are more often necessary in high-risk patients, such as the elderly. However, the impact of influ...
108 citations
TL;DR: It is critical to discuss the key issues for the long-term success of the vaccine which include strain coverage, potential persistence of protection, potential effects on carriage of MenB strains, potential for escape mutants and cost effectiveness.
Abstract: Serogroup B meningococcal (MenB) disease remains a serious public health problem for which a cross-protective vaccine effective against a wide range of MenB isolates has not been available. Novartis Vaccines has developed a vaccine for the prevention of MenB disease that contains four antigenic components: factor H binding protein (fHbp), neisserial adhesin A (NadA), Neisseria heparin binding antigen (NHBA) and outer membrane vesicles from a New Zealand epidemic strain (which provides PorA). This vaccine has been submitted for regulatory review in Europe so it is timely to review the design of the vaccine, results to date in clinical studies and the potential strain coverage provided by the vaccine. It is also critical to discuss the key issues for the long-term success of the vaccine which include strain coverage, potential persistence of protection, potential effects on carriage of MenB strains, potential for escape mutants and cost effectiveness.
108 citations
TL;DR: The various social determinants affecting routine immunization programs in low-, middle- and high-income countries and possible interventions to address them are explored.
Abstract: Vaccine preventable diseases have been responsible for a significant portion of childhood mortality in low-income countries, and have been re-emerging in medium- and high-income countries. The effectiveness of routine childhood immunization programs relies on multiple factors. Social determinants have the potential to affect immunization programs around the world, with globalization and ease of communication facilitating their effect. Exploring the types of social determinants affecting immunization efforts in various countries is of great importance to the ability of nations to address them, prevent the spread of disease and lower mortality rates. The social determinants affecting vaccination programs can vary among countries of different income levels, with some social determinants overlapping among these country groups. In this article we explore the various social determinants affecting routine immunization programs in low-, middle- and high-income countries and possible interventions to address them.
98 citations
TL;DR: Suggestions are made on possible directions for future research on the development of vaccines against T. gondii as well as on the difficulties along with challenges, such as vaccine construct, mode of vaccine administration and standardization of immunization evaluation.
Abstract: Toxoplasma gondii is a ubiquitous protozoan parasite that can infect a wide range of animals including humans. This single known species in the genus Toxoplasma is considered as one of the most successful eukaryotic pathogens which is of major medical and veterinary importance. Effective vaccines may contribute toward preventing and controlling the spread of toxoplasmosis. The present communication addresses the current status of development of vaccines against T. gondii. Further discussion is made on the difficulties along with challenges, such as vaccine construct, mode of vaccine administration and standardization of immunization evaluation. Finally suggestions are made on possible directions for future research on the development of vaccines against T. gondii.
TL;DR: This review outlines important considerations in designing a vaccine for the prevention of S. aureus disease in healthcare settings based on multiple important bacterial pathogenesis mechanisms.
Abstract: Staphylococcus aureus is a major cause of healthcare-associated infections and is responsible for a substantial burden of disease in hospitalized patients Despite increasingly rigorous infection control guidelines, the prevalence and corresponding negative impact of S aureus infections remain considerable Difficulties in controlling S aureus infections as well as the associated treatment costs are exacerbated by increasing rates of resistance to available antibiotics Despite ongoing efforts over the past 20 years, no licensed S aureus vaccine is currently available However, learnings from past clinical failures of vaccine candidates and a better understanding of the immunopathology of S aureus colonization and infection have aided in the design of new vaccine candidates based on multiple important bacterial pathogenesis mechanisms This review outlines important considerations in designing a vaccine for the prevention of S aureus disease in healthcare settings
TL;DR: The first prophylactic vaccine against hepatitis E virus (HEV) infection and the HEV associated disease was approved by China's State Food and Drug Administration in December 2011.
Abstract: The first prophylactic vaccine, Hecolin®, against hepatitis E virus (HEV) infection and the HEV associated disease was approved by China's State Food and Drug Administration (SFDA) in December 2011. Key milestones during the 14-year HEV vaccine development are summarized in this commentary. After years of innovative research the recombinant virus-like particle (VLP) based antigen with virion-like epitopes was successfully produced in E. coli production platform on a commercial scale. Safety and efficacy of this vaccine was demonstrated in a large scale phase III clinical trial.
TL;DR: Although it is difficult to have a clear picture of vaccine benefits and harms examining single systematic reviews, the main findings are compiled and which could be the most reasonable explanations for some differences in findings (or their interpretation) across previously published meta-analyses are evaluated.
Abstract: Fifteen meta-analyses have been published between 1995 and 2011 to evaluate the efficacy/effectiveness and harms of diverse influenza vaccines—seasonal, H5N1 and 2009(H1N1) —in various age-classes (healthy children, adults or elderly). These meta-analyses have often adopted different analyses and study selection criteria. Because it is difficult to have a clear picture of vaccine benefits and harms examining single systematic reviews, we compiled the main findings and evaluated which could be the most reasonable explanations for some differences in findings (or their interpretation) across previously published meta-analyses. For each age group, we performed analyses that included all trials that had been included in at least one relevant meta-analysis, also exploring whether effect sizes changed over time. Although we identified several discrepancies among the meta-analyses on seasonal vaccines for children and elderly, overall most seasonal influenza vaccines showed statistically significant efficacy/eff...
TL;DR: Seropositivity rates and geometric mean neutralizing antibody titers against all four dengue virus serotypes increased in all age groups after each of the three CYD-TDV doses, and support the continued development of CYD -TDV for the prevention of d Dengue disease.
Abstract: This was a multicenter, blinded, Phase II study (NCT00880893) conducted in Singapore. The primary objectives were to evaluate the safety of a tetravalent dengue vaccine (TDV) comprising four recomb...
TL;DR: Overall, the poxvirus vectors have proven to be excellent HIV/AIDS vaccine candidates, with distinct behavior among them, and the future implementation will be dictated by their optimized immune profile in clinical trials.
Abstract: The RV144 phase III clinical trial with the combination of the poxvirus vector ALVAC and the HIV gp120 protein has taught us that a vaccine against HIV/AIDS is possible but further improvements are...
TL;DR: The approval of Sip-T based on a survival benefit and very tolerable safety profile will enhance the ability to care for men with advanced prostate cancer, allow for further investigations of this approach in combination with others therapies with different mechanisms of action and non-overlapping toxicities, and allow further investigations earlier in the course of the disease.
Abstract: Sipuleucel-T (Provenge) (Sip-T) is first -in class as a therapeutic autologous vaccine approved for the treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. This product is the culmination of decades of basic immunological and prostate cancer investigations and 13 y of clinical trial investigations. Sip-T represents a paradigm shift in cancer therapeutics and represents the first approved autologous therapeutic cancer vaccine, which has demonstrated a survival benefit. The potential benefit of this product is the excellent risk to benefit ratio, which will allow for the combination of this approach with other more toxic therapies. The favorable risk to benefit will also afford the opportunity for trials investigating this product earlier in the disease state and in combination with local therapies. The ability to target more localized or lower volume disease will maximize the therapeutic benefit over a longer period of time. The novelty of the platform of this approach could be used to treat any cancer with a tumor-specific cell surface target. The main product of Sip-T is the re-infusion of a patient's antigen presenting cells from leukapheresis after ex-vivo exposure to a chimeric protein of human GM-CSF and PAP. In metastatic CRPC patients three infusions of these activated cells over a month lead to statistically significant 4.1 mo increase in median survival and a 22.5% reduction in risk of death. The main side effect from this re-infusion of activated immune cells is a "flu-like" syndrome that includes chills, fatigue, fevers, back pain, nausea, joints aches and headaches in decreasing order of frequency. Immune monitoring during the clinical trials also demonstrated a specific cellular and antibody immune response, suggesting the proposed mechanism of adoptive immunotherapy to PAP was behind this survival benefit. This product also serves as a proof of principle for targeted immunotherapy for others cancers with defined cell surface markers. In summary, the approval of Sip-T based on a survival benefit and very tolerable safety profile will 1) enhance our ability to care for men with advanced prostate cancer, 2) allow for further investigations of this approach in combination with others therapies with different mechanisms of action and non-overlapping toxicities, and 3) allow further investigations earlier in the course of the disease.
TL;DR: This revival is mainly due to the successful use and extensive characterization of VACV as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector.
Abstract: In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses,...
TL;DR: This review is to give a succinct but comprehensive overview of electroporation as a delivery modality including electrotransfer to skin and muscle and speculate and discuss future uses for this powerful electrotransfer technology.
Abstract: Vaccinations are increasingly used to fight infectious disease, and DNA vaccines offer considerable advantages, including broader possibilities for vaccination and lack of need for cold storage. It has been amply demonstrated, that electroporation augments uptake of DNA in both skin and muscle, and it is foreseen that future DNA vaccination may to a large extent be coupled with and dependent upon electroporation based delivery. Understanding the basic science of electroporation and exploiting knowledge obtained on optimization of DNA electrotransfer to muscle and skin, may greatly augment efforts on vaccine development. The purpose of this review is to give a succinct but comprehensive overview of electroporation as a delivery modality including electrotransfer to skin and muscle. As well, this review will speculate and discuss future uses for this powerful electrotransfer technology.
TL;DR: Functional in vitro assays such as the growth/invasion inhibition assays (GIA) are widely used, but it is unclear whether GIA activity correlates with protection or predicts vaccine efficacy, and more work is needed to establish the utility of GIA for blood-stage vaccine development.
Abstract: An effective vaccine against P. falciparum malaria remains a global health priority. Blood-stage vaccines are an important component of this effort, with some indications of recent progress. However only a fraction of potential blood-stage antigens have been tested, highlighting a critical need for efficient down-selection strategies. Functional in vitro assays such as the growth/invasion inhibition assays (GIA) are widely used, but it is unclear whether GIA activity correlates with protection or predicts vaccine efficacy. While preliminary data in controlled human malaria infection (CHMI) studies indicate a possible association between in vitro and in vivo parasite growth rates, there have been conflicting results of immunoepidemiology studies, where associations with exposure rather than protection have been observed. In addition, GIA-interfering antibodies in vaccinated individuals from endemic regions may limit assay sensitivity in heavily malaria-exposed populations. More work is needed to establish ...
TL;DR: Co-delivery of IL-12 DNA with the SIV DNA vaccine enhanced the magnitude and breadth of immune responses in immunized rhesus macaques, and supports the inclusion of IL -12 DNA as vaccine adjuvant.
Abstract: Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the d...
TL;DR: To improve the effectiveness of these vaccines, a better understanding of the mechanisms of protection, virological control and immune deterioration is required; without this knowledge, an efficacious therapeutic vaccine will remain elusive.
Abstract: Resistance to medication, adverse effects in the medium-to-long-term and cost all place important limitations on lifelong adherence to combined antiretroviral therapy (cART). In this context, new therapeutic alternatives to 'cART for life' in HIV-infected patients merit investigation. Some data suggest that strong T cell-mediated immunity to HIV can indeed limit virus replication and protect against CD4 depletion and disease progression. The combination of cART with immune therapy to restore and/or boost immune-specific responses to HIV has been proposed, the ultimate aim being to achieve a 'functional cure'. In this scenario, new, induced, HIV-specific immune responses would be able to control viral replication to undetectable levels, mimicking the situation of the minority of patients who control viral replication without treatment and do not progress to AIDS. Classical approaches such as whole inactivated virus or recombinant protein initially proved useful as therapeutic vaccines. Overall, however, the ability of these early vaccines to increase HIV-specific responses was very limited and study results were discouraging, as no consistent immunogenicity was demonstrated and there was no clear impact on viral load. Recent years have seen the development of new approaches based on more innovative vectors such as DNA, recombinant virus or dendritic cells. Most clinical trials of these new vectors have demonstrated their ability to induce HIV-specific immune responses, although they show very limited efficacy in terms of controlling viral replication. However, some preliminary results suggest that dendritic cell-based vaccines are the most promising candidates. To improve the effectiveness of these vaccines, a better understanding of the mechanisms of protection, virological control and immune deterioration is required; without this knowledge, an efficacious therapeutic vaccine will remain elusive.
TL;DR: From a regulatory, economic and market acceptability standpoint, FI-EV71 virion vaccines are the most promising candidates and are currently being evaluated in human clinical trials.
Abstract: Enterovirus 71 (EV71) is now recognized as an emerging neurotropic virus in Asia and with Coxsackie virus (CV) it is the other major causative agent of hand-foot-mouth diseases (HFMD). Effective me...
TL;DR: The applicability of this technology to study the immunization process, construction of new vaccines and development of safer and more efficient delivery strategies has been described.
Abstract: Phage display is a powerful technique in medical and health biotechnology. This technology has led to formation of antibody libraries and has provided techniques for fast and efficient search of these libraries. The phage display technique has been used in studying the protein-protein or protein-ligand interactions, constructing of the antibody and antibody fragments and improving the affinity of proteins to receptors. Recently phage display has been widely used to study immunization process, develop novel vaccines and investigate allergen-antibody interactions. This technology can provide new tools for protection against viral, fungal and bacterial infections. It may become a valuable tool in cancer therapies, abuse and allergies treatment. This review presents the recent advancements in diagnostic and therapeutic applications of phage display. In particular the applicability of this technology to study the immunization process, construction of new vaccines and development of safer and more efficient delivery strategies has been described.
TL;DR: The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines.
Abstract: The influenza pandemic of 2009 demonstrated the inability of the established global capacity for egg-based vaccine production technology to provide sufficient vaccine for the population in a timely fashion. Several alternative technologies for developing influenza vaccines have been proposed, among which non-replicating virus-like particles (VLPs) represent an attractive option because of their safety and immunogenic characteristics. VLP vaccines against pandemic influenza have been developed in tobacco plant cells and in Sf9 insect cells infected with baculovirus that expresses protein genes from pandemic influenza strains. These technologies allow rapid and large-scale production of vaccines (3–12 weeks). The 2009 influenza outbreak provided an opportunity for clinical testing of a pandemic influenza VLP vaccine in the midst of the outbreak at its epicenter in Mexico. An influenza A(H1N1)2009 VLP pandemic vaccine (produced in insect cells) was tested in a phase II clinical trial involving 4,563 healthy adults. Results showed that the vaccine is safe and immunogenic despite high preexisting anti-A(H1N1)2009 antibody titers present in the population. The safety and immunogenicity profile presented by this pandemic VLP vaccine during the outbreak in Mexico suggests that VLP technology is a suitable alternative to current influenza vaccine technologies for producing pandemic and seasonal vaccines.
TL;DR: In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV.
Abstract: Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults. Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ≥ 25% and if the nadir CD4...
TL;DR: In this paper, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues.
Abstract: Allergen-specific immunotherapy is currently performed via either the subcutaneous or sublingual routes as a treatment for type I (IgE dependent) allergies. Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts in the absence of any immunopotentiator. Adjuvants to be included in the future in products for allergen specific immunotherapy should ideally enhance Th1 and CD4+ regulatory T cell responses. Imunomodulators impacting dendritic or T cell functions to induce IL10, IL12 and IFNγ production are being investigated in preclinical allergy models. Such candidate adjuvants encompass synthetic or biological immunopotentiators such as glucocorticoids, 1,25-dihydroxy vitamin D3, selected probiotic strains (e.g., Lactobacillus and Bifidobacterium species) as well as TLR2 (Pam3CSK4), TLR4 (monophosphoryl lipid A, synthetic lipid A analogs) or TLR9 (CpGs) ligands. Furthermore, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are being considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues.
TL;DR: The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches.
Abstract: Influenza vaccine preparations have been administered to humans since the late 1930s,1 and the diversity of approaches in licensed trivalent seasonal or monovalent pandemic products is unparalleled by vaccines against any other target. These approaches include inactivated whole virus vaccines, detergent or solvent “split” vaccines, subunit vaccines, live attenuated vaccines, adjuvanted vaccines, intramuscular vaccines, intradermal vaccines, intranasal vaccines, egg-produced vaccines and mammalian cell culture-produced vaccines. The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches. This review describes some of the new approaches to influenza immunization that are the subjects of active research and development.
TL;DR: The economic model for a Chagas’ therapeutic vaccine in Mexico suggests that a vaccine would be highly cost-effective and in many cases economically dominant (providing both cost savings and health benefits) throughout a range of protection durations, severe adverse event risk, and dosing regimens and would be most likely to provide a positive return on investment if the vaccine prevented (rather than delayed) the onset of cardiomyopathy.
Abstract: The health burden of Chagas’ disease (resulting from Trypanosoma cruzi infection) in Latin America (estimated to outweigh that of malaria by 5-fold and affect 2–6 million people in Mexico alone) has motivated development of therapeutic vaccines to prevent infection progression to severe disease. Our economic model for a Chagas’ therapeutic vaccine in Mexico suggests that a vaccine would be highly cost-effective and in many cases economically dominant (providing both cost savings and health benefits) throughout a range of protection durations, severe adverse event risk, and dosing regimens and would be most likely to provide a positive return on investment if the vaccine prevented (rather than delayed) the onset of cardiomyopathy.
TL;DR: Conjugating to Salmonella proteins (flagellin, porins) may extend immune responses to another relevant target for antibody generation and enhance the glyconjugate’s efficacy.
Abstract: Salmonella enterica serovars Typhi and Paratyphi A and B and certain non-typhoidal Salmonella enterica (NTS) serovars are important causes of invasive Salmonella disease worldwide. NTS serovars Typ...