Showing papers in "Expert Review of Vaccines in 2013"

The history of MF59® adjuvant: a phoenix that arose from the ashes

Abstract: The first clinical trial of an MF59(®)-adjuvanted influenza vaccine (Novartis) was conducted 20 years ago in 1992. The product that emerged (Fluad(®), Novartis) was licensed first in Italy in 1997 and is now licensed worldwide in 30 countries. US licensure is expected in the coming years. By contrast, many alternative adjuvanted vaccines have failed to progress. The key decisions that allowed MF59 to succeed in such a challenging environment are highlighted here and the lessons that were learned along the way are discussed. MF59 was connected to vaccines that did not succeed and was perceived as a 'failure' before it was a success. Importantly, it never failed for safety reasons and was always well tolerated. Even when safety issues have emerged for alternative adjuvants, careful analysis of the substantial safety database for MF59 have shown that there are no significant concerns with widespread use, even in more 'sensitive' populations.

The use of Toll-like receptor 7/8 agonists as vaccine adjuvants

Abstract: Small molecule Toll-like receptor (TLR) 7/8 agonists have demonstrated potential as vaccine adjuvants, since they directly activate APCs and can enhance both humoral and cellular immune responses, especially Th1 responses. Although the natural ligands for TLR7 and TLR8 are ssRNA, the vast majority of vaccine studies performed thus far have been performed with synthetic small molecule imidazoquinolines, such as imiquimod and resiquimod. Despite the approved clinical use of the topical TLR7 agonist, imiquimod (Aldara(®) Imiquimod 5% cream; 3M, MN, USA), for external genital warts, superficial basal cell carcinoma and actinic keratosis, no vaccines using TLR7, TLR8 or TLR7/8 agonists have progressed beyond early-phase clinical studies thus far. This review will highlight the nonclinical and clinical studies that indicate promise for TLR7/8 ligands as vaccine adjuvants, reasons for inconsistent results thus far, problems with current technology and potential paths forward for TLR7/8 agonists as vaccine adjuvants.

The evolving history of influenza viruses and influenza vaccines

Abstract: The isolation of influenza virus 80 years ago in 1933 very quickly led to the development of the first generation of live-attenuated vaccines. The first inactivated influenza vaccine was monovalent (influenza A). In 1942, a bivalent vaccine was produced after the discovery of influenza B. It was later discovered that influenza viruses mutated leading to antigenic changes. Since 1973, the WHO has issued annual recommendations for the composition of the influenza vaccine based on results from surveillance systems that identify currently circulating strains. In 1978, the first trivalent vaccine included two influenza A strains and one influenza B strain. Currently, there are two influenza B lineages circulating; in the latest WHO recommendations, it is suggested that a second B strain could be added to give a quadrivalent vaccine. The history of influenza vaccine and the associated technology shows how the vaccine has evolved to match the evolution of influenza viruses.

Salmonella vaccines in poultry: past, present and future

Abstract: Salmonella species are important zoonotic pathogens that cause gastrointestinal disease in humans and animals. Poultry products contaminated with these pathogens are one of the major sources of human Salmonella infections. Vaccination of chickens, along with other intervention measures, is an important strategy that is currently being used to reduce the levels of Salmonella in poultry flocks, which will ultimately lead to lower rates of human Salmonella infections. However, despite numerous studies that have been performed, there is still a need for safer, well-defined Salmonella vaccines. This review examines the different classes of Salmonella vaccines that have been tested, highlighting the merits and problems of each, and provides an insight into the future of Salmonella vaccines and the platforms that can be used for delivery.

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

Abstract: With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Vaccines against Toxoplasma gondii: new developments and perspectives.

Abstract: Toxoplasmosis caused by the protozoan Toxoplasma gondii is a major public health problem, infecting one-third of the world human beings, and leads to abortion in domestic animals. A vaccine strategy would be an ideal tool for improving disease control. Many efforts have been made to develop vaccines against T. gondii to reduce oocyst shedding in cats and tissue cyst formation in mammals over the last 20 years, but only a live-attenuated vaccine based on the S48 strain has been licensed for veterinary use. Here, the authors review the recent development of T. gondii vaccines in cats, food-producing animals and mice, and present its future perspectives. However, a single or only a few antigen candidates revealed by various experimental studies are limited by only eliciting partial protective immunity against T. gondii. Future studies of T. gondii vaccines should include as many CTL epitopes as the live attenuated vaccines.

Immunological assessment of influenza vaccines and immune correlates of protection.

Abstract: Influenza vaccines remain the primary public health tool in reducing the ever-present burden of influenza and its complications. In seeking more immunogenic, more effective and more broadly cross-protective influenza vaccines, the landscape of influenza vaccines is rapidly expanding, both in near-term advances and next-generation vaccine design. Although the first influenza vaccines were licensed over 60 years ago, the hemagglutination-inhibition antibody titer is currently the only universally accepted immune correlate of protection against influenza. However, hemagglutination-inhibition titers appear to be less effective at predicting protection in populations at high risk for severe influenza disease; older adults, young children and those with certain medical conditions. The lack of knowledge and validated methods to measure alternate immune markers of protection against influenza remain a substantial barrier to the development of more immunogenic, broadly cross-reactive and effective influenza vaccines. Here, the authors review the knowledge of immune effectors of protection against influenza and discuss assessment methods for a broader range of immunological parameters that could be considered in the evaluation of traditional or new-generation influenza vaccines.

Virus-like particles for the prevention of human papillomavirus-associated malignancies.

Abstract: As compared with peptide- or protein-based vaccines, naked DNA vectors and even traditional attenuated or inactivated virus vaccines, virus-like particles (VLPs) are an attractive vaccine platform, as they offer a combination of safety, ease of production and both high-density B-cell epitope display and intracellular presentation of T-cell epitopes that induce potent humoral and cellular immune responses, respectively. Indeed, HPV vaccines based on VLP production by recombinant expression of major capsid antigen L1 in yeast (Gardasil®, Merck & Co., NJ, USA) or insect cells (Cervarix®, GlaxoSmithKline, London, UK) have been licensed for the prevention of cervical and anogenital infection and disease associated with the genotypes targeted by each vaccine. However, these HPV vaccines have not been demonstrated as effective to treat existing infections, and efforts to develop a therapeutic HPV vaccine continue. Furthermore, current HPV L1-VLP vaccines provide type-restricted protection, requiring highly multi...

HLA ligandome tumor antigen discovery for personalized vaccine approach

Abstract: Every cancer is different and cancer cells differ from normal cells, in particular, through genetic alterations. HLA molecules on the cell surface enable T lymphocytes to recognize cellular alterations as antigens, including mutations, increase in gene product copy numbers or expression of genes usually not used in the adult organism. The search for cancer-associated antigens shared by many patients with a particular cancer has yielded a number of hits used in clinical vaccination trials with indication of survival benefit. Targeting cancer-specific antigens, which are exclusively expressed on cancer cells and not on normal cells, holds the promise for much better results and perhaps even a cure. Such antigens, however, may specifically appear in very few patients or may be mutated appearing just in one patient. Therefore, to target these in a molecularly defined way, the approach has to be individualized.

Virus-like particles produced in plants as potential vaccines

Abstract: Virus-like particles (VLPs) have been produced as candidate vaccines in plants virtually since the introduction of biofarming. Even today, VLPs remain the best candidates for safe, immunogenic, efficacious and inexpensive vaccines. Well-characterized human animal viruses such as HBV, HCV, HIV and HPV, rotaviruses, norovirus, foot and mouth disease viruses and even influenza virus proteins have all been successfully investigated for VLP formation. Proteins have been produced in transgenic plants and via transient expression techniques; simple structures, structures depending on more than one protein, naked and enveloped particles have all been made. There have been multiple proofs of concept, more than a few proofs of efficacy, and several products moved into human trials. This review will cover the history of VLP production in plants, and will explore a few examples in detail to illustrate the potential of such a mode of production for human and animal medicine.

Development of Vi conjugate – a new generation of typhoid vaccine

Abstract: Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination.

Dengue vaccines: recent developments, ongoing challenges and current candidates

Abstract: Dengue is among the most prevalent and important arbovirus diseases of humans. To effectively control this rapidly spreading disease, control of the vector mosquito and a safe and efficacious vaccine are critical. Despite considerable efforts, the development of a successful vaccine has remained elusive. Multiple factors have complicated the creation of a successful vaccine, not the least of which are the complex, immune-mediated responses against four antigenically distinct serotypes necessitating a tetravalent vaccine providing long-lasting protective immunity. Despite the multiple impediments, there are currently many promising vaccine candidates in preclinical and clinical development. Here, the recent advances in dengue virus vaccine development are reviewed and the challenges associated with the use of these vaccines as a public health tool are briefly discussed.

The genetic basis for interindividual immune response variation to measles vaccine: new understanding and new vaccine approaches.

Abstract: The live-attenuated measles vaccine is effective, but measles outbreaks still occur in vaccinated populations. This warrants elucidation of the determinants of measles vaccine-induced protective immunity. Interindividual variability in markers of measles vaccine-induced immunity, including neutralizing antibody levels, is regulated in part by host genetic factor variations. This review summarizes recent advances in our understanding of measles vaccine immunogenetics relative to the perspective of developing better measles vaccines. Important genetic regulators of measles vaccine-induced immunity, such as HLA class I and HLA class II genotypes, single nucleotide polymorphisms in cytokine/cytokine receptor genes (IL12B, IL12RB1, IL2, IL10) and the cell surface measles virus receptor CD46 gene, have been identified and independently replicated. New technologies present many opportunities for identification of novel genetic signatures and genetic architectures. These findings help explain a variety of immune response-related phenotypes and promote a new paradigm of 'vaccinomics' for novel vaccine development.

Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials

Abstract: Replication-defective chimpanzee adenovirus vectors are emerging as a promising new class of genetic vaccine carriers. Chimpanzee adenovirus vectors have now reached the clinical stage and appear to be endowed with all the properties needed for human vaccine development, including high quality and magnitude of the immune response induced against the encoded antigens, good safety and ease of manufacturing on a large-scale basis. Here the authors review the recent findings of this novel class of adenovirus vectors and compare their properties to other clinical stage vaccine vectors derived from poxvirus, alphavirus and human adenovirus.

Insect cells as a production platform of complex virus-like particles.

Abstract: Virus-like particles (VLPs) are multiprotein structures that resemble the conformation of native viruses but lack a viral genome, potentiating their application as safer and cheaper vaccines. The production of VLPs has been strongly linked with the use of insect cells and the baculovirus expression vector system, especially those particles composed of two or more structural viral proteins. In fact, this expression platform has been extensively improved over the years to address the challenges of coexpression of multiple proteins and their proper assembly into complexes in the same cell. In this article, the role of insect cell technology in the development and production of complex VLPs is overviewed; recent achievements, current bottlenecks and future trends are also highlighted.

Social and psychological factors underlying adult vaccination behavior: lessons from seasonal influenza vaccination in the US and the UK

Abstract: This article reviews the evidence base on the social and psychological factors that facilitate or hinder vaccination among adults. The authors categorized these factors into eight themes: social influence, disease-related factors, vaccine-related factors, habit, general attitudes toward health and vaccines, awareness and knowledge, practical barriers and motivators and altruism. Although there were many commonalities between both settings, the authors also indentifiedimportant differences. A better understanding of social and psychological aspects of vaccination across contexts and vaccines remains a priority.

Live-attenuated bacteria as a cancer vaccine vector.

Abstract: In the emerging field of active and specific cancer immunotherapy, strategies using live-attenuated bacterial vectors have matured in terms of academic and industrial development. Different bacterial species can be genetically engineered to deliver antigen to APCs with strong adjuvant effects due to their microbial origin. Proteic or DNA-encoding antigen delivery routes and natural bacterial tropisms might differ among species, permitting different applications. After many academic efforts to resolve safety and efficacy issues, some firms have recently engaged clinical trials with live Listeria or Salmonella spp. We describe here the main technological advances that allowed bacteria to become one of the most promising vectors in cancer immunotherapy.

Clinical applications of attenuated MVA poxvirus strain.

Abstract: The highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA) has reached maturity as a vector delivery system and as a vaccine candidate against a broad spectrum of diseases. This has been largely recognized from research on virus-host cell interactions and immunological studies in pre-clinical and clinical trials. This review addresses the studies of MVA vectors used in phase I/II clinical trials, with the aim to provide the main findings obtained on their behavior when tested against relevant human diseases and cancer and also highlights the strategies currently implemented to improve the MVA immunogenicity. The authors assess that MVA vectors are progressing as strong vaccine candidates either alone or when administered in combination with other vectors.

Norovirus virus-like particle vaccines for the prevention of acute gastroenteritis.

Abstract: Noroviruses (NoVs) are the most common cause of nonbacterial acute gastroenteritis in humans worldwide. These highly infectious viruses were, until recently, commonly thought to cause a mild, self-limiting disease in healthy individuals, but increasing epidemiology shows that the incidence and severity of illness due to NoV infection is substantial and similar to diseases where immunization is widely recommended. Human NoV challenge studies have identified carbohydrate histo-blood group antigen expression as an important human susceptibility factor for many strains and correspondingly, that antibodies which block carbohydrate virus binding represent a potential correlate of protection against NoV infection and illness. Since human NoVs do not replicate in cell culture, there are numerous challenges to the development of a vaccine to prevent illness or infection. However, the development of NoV virus-like particles (VLPs) has enabled significant progress toward effective vaccine candidates designed to protect against multiple circulating NoV strains. Vaccination with NoV VLP vaccines has been shown to both induce antibodies that block virus-derived VLP carbohydrate binding and protect against homologous viral challenge in a human clinical study.

An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma.

Abstract: Outcome for glioblastoma (GBM), the most common primary CNS malignancy, remains poor. The overall survival benefit recently achieved with immunotherapeutics for melanoma and prostate cancer support evaluation of immunotherapies for other challenging cancers, including GBM. Much historical dogma depicting the CNS as immunoprivileged has been replaced by data demonstrating CNS immunocompetence and active interaction with the peripheral immune system. Several glioma antigens have been identified for potential immunotherapeutic exploitation. Active immunotherapy studies for GBM, supported by preclinical data, have focused on tumor lysate and synthetic antigen vaccination strategies. Results to date confirm consistent safety, including a lack of autoimmune reactivity; however, modest efficacy and variable immunogenicity have been observed. These findings underscore the need to optimize vaccination variables and to address challenges posed by systemic and local immunosuppression inherent to GBM tumors. Additional immunotherapy strategies are also in development for GBM. Future studies may consider combinatorial immunotherapy strategies with complimentary actions.

Measles elimination: progress, challenges and implications for rubella control

Abstract: Measles and rubella are major vaccine-preventable causes of child mortality and disability They have been eliminated from the Americas and some other regions have also come close to elimination In this paper, we review regional progress toward measles and rubella control/elimination goals, describe the recent epidemiology of these infections and discuss challenges to achieving the goals Globally, measles vaccination is estimated to prevent nearly 2 million deaths each year Despite this remarkable progress, large measles outbreaks have occurred in recent years, often involving older persons who were not vaccinated in earlier years Such an occurrence would be particularly damaging for rubella control programmes as it could lead to peaks in congenital rubella syndrome Challenges to achieving and sustaining high vaccination coverage include civil conflict, weak health systems, geographic, cultural and economic barriers to reaching certain population groups and inadequate monitoring and use of data for action Countries and regions aiming to eliminate measles and control rubella urgently need to improve the implementation and monitoring of both routine and mass vaccination campaign strategies

Hepatitis B core-based virus-like particles to present heterologous epitopes.

Abstract: Since the first effort to recombinantly express the hepatitis B core protein (HBc) in bacteria, the remarkable virion-like structure has fuelled interest in unraveling the structural and antigenic properties of this protein. Initial studies proved HBc virus-like particles to possess strong immunogenic properties, which can be conveyed to linked antigens. More than 35 years later, numerous studies have been performed using HBc as a carrier protein for antigens derived from over a dozen different pathogens and diseases. In this review, the authors highlight the intriguing features of HBc as carrier and antigen, illustrated by some examples and experimental results that underscore the value of HBc as an antigen-presenting platform. Two of these HBc fusions, targeting influenza A and malaria, have even progressed into clinical testing. In the future, the HBc-based virus-like particles platform will probably continue to be used for the display of poorly immunogenic antigens, mainly because virus-like particle formation by HBc capsomers is compatible with nearly any available recombinant gene expression system.

Dendritic cells in cancer immunotherapy: vaccines and combination immunotherapies.

Abstract: Dendritic cells (DCs) are specialized immunostimulatory cells involved in the induction and regulation of immune responses. The feasibility of large-scale ex vivo generation of DCs from patients’ monocytes allows for therapeutic application of ex vivo-cultured DCs to bypass the dysfunction of endogenous DCs, restore immune surveillance, induce cancer regression or stabilization or delay or prevent its recurrence. While the most common paradigm of the therapeutic application of DCs reflects their use as cancer ‘vaccines’, additional and potentially more effective possibilities include the use of patients’ autologous DCs as parts of more comprehensive therapies involving in vivo or ex vivo induction of tumor-reactive T cells and the measures to counteract systemic and local immunosuppression in tumor-bearing hosts. Ex vivo-cultured DCs can be instructed to acquire distinct functions relevant for the induction of effective cancer immunity (DC polarization), such as the induction of different effector functions or different homing properties of tumor-specific T cells (delivery of ‘signal 3’ and ‘signal 4’). These considerations highlight the importance of the application of optimized conditions for the ex vivo culture of DCs and the potential combination of DC therapies with additional immune interventions to facilitate the entry of DC-induced T cells to tumor tissues and their local antitumor functions.

Human papillomavirus therapeutic vaccines: targeting viral antigens as immunotherapy for precancerous disease and cancer.

Abstract: Infections with oncogenic HPV types have the potential to lead to the induction of several types of cancer, notably cervical, vulvar, anal, and head and neck cancer. While prophylactic vaccines are currently available and show high efficacy against the establishment of HPV infection, low rates of initiation and lower rates of completion of the vaccination regimen, as well as the lack of an opportunity to be vaccinated prior to infection, has lead to the development of a patient population for whom no immune-based therapy for infection is available. In the current review the authors examine clinical approaches to HPV-targeted immune therapies, the bulk of which target the regulatory proteins E6 and E7 that are constitutively expressed in HPV-associated cancer cells. Early studies demonstrate a correlation between induction of T-cell responses and clearance of HPV-associated precancerous lesions. The clinical data corroborates these findings and highlight the importance of Th1 skewing. Improvements in our understanding of tumor immunology and development of more potent Th1-directed vaccine platforms make it feasible to foresee a HPV therapeutic vaccine in the coming years.

Combination of Adjuvants: The Future of Vaccine Design

Abstract: It is thought that the development of vaccines for the treatment of infectious diseases and cancer is likely to be achieved in the coming decades. This is partially due to a better understanding of the regulatory networks connecting innate with adaptive immune responses. The innate immune response is triggered by the recognition of conserved pathogen-associated molecular patterns by germ line-coded pattern recognition receptors. Several families of pattern recognition receptors have been characterized, including Toll-like receptors and nucleotide-binding domain receptors. The identification of their ligands has driven the development of novel adjuvants many of which have been tested in vaccine clinical trials. Here, the authors review recent preclinical data and clinical trial results supporting the view that combinations of adjuvants are the way forward in vaccine design. Multiadjuvanted vaccines can stimulate the broad and robust protective immune responses required to fight chronic infectious diseases and cancer.

A multicomponent serogroup B meningococcal vaccine is licensed for use in Europe: what do we know, and what are we yet to learn?

Abstract: The first meningococcal vaccine with the potential to provide broad coverage against serogroup B disease has recently been approved for use in Europe. This vaccine, multi-component serogroup B vaccine (4CMenB), contains recombinant proteins and outer membrane vesicles, and has been extensively studied in clinical trials involving over 7500 adults, children and infants. As well as demonstrating immunogenicity against a range of serogroup B meningococcal strains, these trials have also demonstrated relatively high rates of fever following infant immunization. This article will summarize the vaccine composition, clinical trials and suggested schedules of this vaccine, with specific attention to immunogenicity, reactogenicity, safety, potential coverage and optimal implementation of this vaccine.

Increasing rates of Salmonella Paratyphi A and the current status of its vaccine development.

Abstract: Enteric fever caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi is still a major disease burden mainly in developing countries. Previously, S. Typhi was believed to be the major cause of enteric fever. The real situation is now becoming clear with reports emerging from many Asian countries of S. Paratyphi, mostly S. Paratyphi A, causing a substantial number of cases of enteric fever. Although there have been advances in the use of the currently available typhoid vaccines and in the development of newer typhoid vaccines, paratyphoid vaccine development is lagging behind. Since the disease caused by S. Typhi and S. Paratyphi are clinically indistinguishable and are commonly termed 'enteric' fever, it will be necessary to have a vaccine available against both S. Typhi and S. Paratyphi A as a bivalent 'enteric fever vaccine'.

Why can't we make an effective vaccine against Helicobacter pylori?

Abstract: Helicobacter pylori is a major human pathogen that colonizes the stomach and is the lead etiological agent for several pathologies. An effective vaccine against these bacteria would be invaluable for protecting against gastric adenocarcinoma. However, the development of such a vaccine has stalled and the field has progressed little in the last decade. In this review, the authors provide an opinion on key problems that are preventing the development of a H. pylori vaccine. Primarily, this involves the inability to produce a completely protective immune response. The knock-on effects of this include a loss of industry investment. Overcoming these problems will likely involve defeating the immune-evasion defenses of H. pylori, in particular the mechanism(s) by which it evades antibody-mediated attack.

Salmonella as a vaccine delivery vehicle.

Abstract: Attenuated Salmonella vaccines can be administered orally to deliver recombinant antigens to mucosal surfaces inducing a protective immune response against a variety of targeted pathogens. A number of exciting new approaches and technologies for attenuated Salmonella vaccines have been developed recently. However, a disconnect remains between results obtained with mice in preclinical studies and results obtained in human clinical trials. This is due to an incomplete understanding of Salmonella Typhi interactions with human hosts and inadequate animal models available for study. In this review, the authors describe recent progress in identifying important differences underlying S. Typhi-host interactions, the development of novel approaches to vaccine design and six recent clinical trials evaluating Salmonella-vectored vaccines.

Recent progress towards development of a Shigella vaccine

Abstract: The burden of dysentery due to shigellosis among children in the developing world is still a major concern. A safe and efficacious vaccine against this disease is a priority, since no licensed vaccine is available. This review provides an update of vaccine achievements focusing on subunit vaccine strategies and the forthcoming strategies surrounding this approach. In particular, this review explores several aspects of the pathogenesis of shigellosis and the elicited immune response as being the basis of vaccine requirements. The use of appropriate Shigella antigens, together with the right adjuvants, may offer safety, efficacy and more convenient delivery methods for massive worldwide vaccination campaigns.