Influenza vaccine: a travelers' vaccine?

Seasonal influenza affects 5-15% of the world's population annually and is considered to be the second most frequent vaccine-preventable infection in travelers. Despite increasing travel volume worldwide, guidelines on influenza vaccination for international travel are scarce. On the basis of some national recommendations, influenza vaccine should be used based on host criteria to usual risk groups, such as old (>50-65 years) or young (6-23 months) age and those with comorbidities. Additionally, environmental and behavioral factors must be considered. Close contact with high transmission has been documented in cruise ships and during mass gatherings. Travelers crossing to the opposite hemisphere in influenza-peak season may need protection. Those visiting the tropics are at moderate risk of infection and illness during the entire year. A summary on existing traveler recommendations relating to avian influenza is included.     

Is an HIV vaccine possible?

Although many new prevention modalities that include the use of antiretroviral drugs show promise, there is no question that a global solution to the HIV epidemic will not be economically or logistically feasible without the development of vaccine that provides durable protection. In the best case scenario, the vaccine has to protect against acquisition of infection, likely mediated by Env-specific B-cell responses combined with CD4+ T-cell responses to evoke full maturation and maintenance of protective antibodies. But HIV-specific CD8+ T-cell responses are also likely to be a key element, particularly for those inevitable situations in which full vaccine-induced protection from acquisition is not achieved, in which case durable control of established infection will be required. Although there is reason to be optimistic that an effective HIV vaccine is possible, one of the major constraints moving forward will likely be constraint on funding to support a diversity of concepts at a time that the correlates of protection from acquisition and disease progression are still unknown. Given the scope of the epidemic and the economic climate, we must strive to do much more with less and seek to access additional resources, both scientific and monetary, from every possible source.     

The seasonal influenza vaccine Agriflu(®)

Seasonal influenza continues to have a large impact annually. Combined with pneumonia, influenza is the sixth leading cause of death in the USA, and vaccination has been the most important tool to prevent it. Agriflu(?) is an egg-derived, subunit, nonadjuvanted trivalent inactivated vaccine indicated for immunization to prevent disease caused by influenza virus subtypes A and B contained in the vaccine. Agriflu was approved in the USA by the US FDA on 27 November 2009, for those aged 18 years and older, to prevent disease caused by influenza virus subtypes A and B. Based on clinical trial evidence, Agriflu has been shown to be safe, with <1% serious adverse event rates, and immunogenic. It has been proven to be highly effective to prevent culture-confirmed influenza and, thus, is an alternative to previously licensed seasonal influenza vaccines. Besides Fluvirin(?), Agriflu is the only subunit vaccine available in the USA. Owing to the economic burden, morbidity and mortality caused by seasonal influenza, addition of new, safe and effective vaccines to the available tools, to reduce the impact of influenza, is of importance and benefit, especially in the face of the recent shortages of influenza vaccines.     

Liposome as vaccine adjuvant and delivery system

Liposomes are artificial, spherical, closed vesicles consisting of one or more lipid bilayer （s）. Liposomes made from ester phospholipids have been studied extensively over the last 3 decades as artificial membrane models. Considerable interest has been generated for applications of liposomes in medicine, including their use as diagnostic reagents, as carrier vehicles in vaccine formulations, or as delivery systems for drugs, genes, or cancer imaging agents . There are now liposomal formulations of conventional drugs that have received clinical approval and many others in clinical trials that bring benefits of reduced toxicity and enhanced efficacy for the treatment of cancer and other life-threatening diseases.     

Will a new vaccine be used?

Despite the fact that vaccines are successful at preventing disease as well as cost-effective, many factors prevent their uptake. These factors are different for different regions. In the United States and Europe, several factors have been identified. The first of these factors is complacency. Both patients and parents lack the knowledge of disease. In addition, physicians are often apathetic about vaccines. There is a lack of training in public health and preventive medicine in that the mind-set of physicians is not directed toward prevention but rather toward treatment. Younger physicians are often less aware of disease controlled by vaccines than their older colleagues are because they have not seen them. One of the paradoxes of vaccines is that success leads to decreased use. Despite the Vaccine for Children's Program, which has provided ample funding for the purchase of vaccines, there are limits on funding for people, facilities, and systematized approaches to maintaining high levels of immunizations. Finally, and perhaps most important, there is fear, real and unfounded. Additionally, in many developing countries there is a lack of focus on preventive medicine, including immunization, as well as limited funding available. Reasonable steps can be taken to overcome these obstacles.     

A safer vaccine for Alzheimer's disease?

Recent reports indicate that amyloid-β (Aβ) vaccine-based therapy for Alzheimer’s disease (AD) may be on the horizon. There are, however, concerns about the safety of this approach. Immunization with Aβ1–42 may not be appropriate in humans because it crosses the blood–brain barrier, can seed fibril formation, and is highly fibrillogenic. Aβ1–42 fibrils can in turn cause inflammation and neurotoxicity. This issue is of a particular concern in the elderly who often do not mount an adequate immune response to vaccines. Our findings show that vaccination with nonamyloidogenic/nontoxic Aβ derivative may be a safer therapeutic approach to impede the progression of Aβ-related histopathology in AD. Although the site of action of the anti-Aβ antibodies has been suggested to be within the brain, peripheral clearance of Aβ may have a greater role in reducing cerebral amyloid plaques in these animals and eventually in AD patients. Antibodies in general are predominantly found outside the central nervous system (CNS) and will, therefore, primarily clear systemic Aβ compared to brain Aβ. This disruption of the equilibrium between central and peripheral Aβ should then result in efflux of Aβ out of the brain, and subsequent removal of plaques. Aβ therapy can be targeted to the periphery, which may result in fewer CNS side effects, such as inflammation. Future Aβ derived vaccines should include T_h epitopes, carriers and/or lipid moieties to enhance antibody production in the elderly, the population predominantly affected by AD.     

HIV vaccine update. DNA vaccination: a promising candidate for a vaccine against HIV-1?

According to animal studies, DNA vaccines employ the genes encoding proteins of pathogens or tumors, in contrast to the more conventional vaccine approaches. In addition, DNA vaccinations do not involve infectious agents, proteins are expressed in their natural form resulting to better recognition of viral proteins by the antibodies, and both strong and durable cellular immune responses as well as neutralizing antibodies are induced. Altogether, this makes DNA vaccinations one of the most promising future candidates in the field of HIV vaccines. However, safety of DNA vaccines should be examined before these vaccines can be considered for large-scale clinical trials in humans. The question of a possible induction of anti-DNA antibodies, with the consequent development of autoimmune manifestations is emphasized. Another is the possible integration of DNA with insertional mutagenesis, which could lead to tumor formation and development of immunologic tolerance of antigen production persists.     

Aflunov(®): a prepandemic influenza vaccine

Influenza viruses are adept in human populations. Indeed, they have the capacity to evade the immune system through mechanisms of mutations (antigenic drift) and major variations in surface protein expression (antigenic shift). When a major change occurs, the risk of a human pandemic arises. Three influenza pandemics occurred during the 20th century, the most serious being the Spanish influenza. The last pandemic of the past century occurred in 1968, and the responsible virus infected an estimated 1-3 million people throughout the world. The first pandemic of the present century occurred in 2009 and was sustained by a H1N1 strain (A/California/07/09). In 1997, a novel avian influenza virus, H5N1, first infected humans in China. Since its emergence, the H5N1 virus has spread from Asia to Europe and Africa, resulting in the infection of millions of poultry and wild birds. So far, 522 human cases and 322 deaths have been reported by the WHO. Many studies have therefore been performed to obtain efficacious and safe H5N1 vaccines. One of these is Aflunov(?). Aflunov is a prepandemic monovalent A/H5N1 influenza vaccine adjuvanted with MF59 produced by Novartis Vaccines and Diagnostics. In nonclinical studies conducted in rabbits, Aflunov proved to be well-tolerated, did not cause maternal or embryo-fetal toxicity, was not teratogenic, and had no effects on postnatal development. In clinical studies, Aflunov proved safe and well-tolerated in infants, children, adolescents, adults and the elderly. In the same subjects, the vaccine elicited robust immunogenicity against both homologous (A/Vietnam/1194/2004 clade 1) and heterologous viral strains (for instance, A/Indonesia/05/2005 or A/Turkey/15/2006) and induced immunologic memory. Thus, in 2010, the CHMP issued a positive opinion on Aflunov and in January 2011 Aflunov was given marketing authorization. This vaccine could be very useful in the event of adaptation of the H5N1 virus to humans, which could cause a new pandemic.     

DNA immunization--a new chance in vaccine research?

A novel class of vaccines, based on the immunization with "naked" DNA, may hold the promise of protecting against human disease without the disadvantages associated with vaccines presently used, and may help to prevent infections which are not curable today. Direct intramuscular or intradermal inoculation of plasmid DNA encoding sequences of viral proteins results in the synthesis of these proteins, causing humoral and/or cellular immune responses in the recipient. Several advantages are associated with DNA immunization, e.g., cheap to produce, heat stability, amenable to genetic manipulation, mimic viral infection, and no risk of reversion to pathogenicity. Nevertheless, some concerns remain regarding their safety, e.g., the possible integration of plasmid DNA into host chromosomes. In summary, the results concerning the efficiency of DNA vaccination demonstrate clearly that these new vaccines may have a promising future in human immunization.     

Are bacterial vaccine antigens T-cell epitope depleted?

For many infectious diseases, protective immunity can be elicited by vaccination with pathogen-derived proteins. Peptides derived from these proteins are bound to major histocompatibility complex (MHC) molecules and presented to T-cell receptors to stimulate an immune response. We show here that, paradoxically, bacterial proteins known experimentally to elicit a protective immune response are relatively depleted in peptides predicted to bind to human MHC alleles. We propose three nonconflicting reasons for this: the lack of precision of current predictive software, the low incidence of hydrophobic residues in vaccine antigens or evolutionary pressure exerted on bacteria by the immune system. We suggest that there is little value in predicting candidate vaccines based on high MHC-binding epitope density.     

Rotarix®: vaccine performance 6 years postlicensure

Rotarix(?) was first licensed in 2004 and rapidly introduced into private and public markets worldwide. In a previous 2009 article, we reviewed the impact of rotavirus-associated disease, the rationale for different vaccines, prelicensure efficacy studies and cost-effectiveness studies for Rotarix. As of September 2011, Rotarix had been licensed in 123 countries in the Americas, Europe, Australia, Africa and Asia, of which 27 have incorporated the vaccine into national or regional immunization programs. The current review intends to provide the reader with further insight into this vaccine, focusing mainly on the new information obtained after a 6-year postlicensure period. This review will provide only a brief summary of prelicensure studies extensively discussed in the previous publication and refer, in more depth, to the worldwide experience with the vaccine, vaccine impact, and safety observed in effectiveness and observational studies, including a particular analysis on protection against rotavirus G2P[4].     

Is AIDS vaccine research at a turning point?

Although initial anti-ENV vaccines have failed, better results may be obtained with "non-ENV" vaccines capable of inducing cell-mediated responses and perhaps mucosal reactions. A turning point in AIDS vaccine research has been reached in that there are three precise questions to answer: 1. Are the protections obtained in monkeys significant and reproducible and could they be made more frequent? 2. Can more frequent, polyepitopic, and long-lasting cell-mediated responses in human subjects be obtained? 3. Is it possible to induce significant mucosal responses? The decision as to whether phase III trials must be launched will depend on answers to these questions. It may be possible to organize international AIDS vaccine research so that these answers could be obtained in 3 to 4 years, but this would require a frank acceleration of the present endeavors.     

Should hepatitis B vaccine be used for infants?

Chronic hepatitis B virus infection causes nearly all the deaths from this virus. As the initial infection occurs without symptoms and decades prior to the onset of cirrhosis and liver cancer, these consequences are rarely recognized as being caused by the virus. Consequently, its public health importance is under-recognized. Safe and effective vaccines have now been available for over 20 years. Concerns have been raised regarding the mercury preservative in vaccines leading to potential toxicity. But the evidence to date does not support any association of hepatitis B vaccine with serious adverse consequences. Protecting infants through immunization is the most effective control strategy. By 2005, over 80% of countries had implemented routine infant immunization. In countries with relatively low rates of hepatitis B virus infection, some have argued to defer immunization until later life. However, these arguments focus on the more visible acute infection. The possible future cost from a single infant infection argues for universal infant hepatitis B immunization--given the very high costs of treating its consequences (e.g., liver transplant) and the very low price of the vaccine.     

Therapeutic vaccine for melanoma: the untouched grail?

Malignant melanoma remains the most lethal form of cancer, especially for those with lymph node involvement or metastases. Owing to its intrinsic nature of highly resistance to conventional chemotherapy and radiotherapy, advanced melanoma was considered by most to be indolent, defying any tempts to cure. For decades, there had been studies on the adjuvant treatment in order to lower recurrence rate and to improve the likelihood of response. Clinical trials are currently ongoing to explore the role of specific active immunotherapy (vaccine) in the treatment of patients with high risk of recurrence and metastasis. The current paper under evaluation described one randomized Phase III trial of the therapeutic vaccine Melacine plus low-dose IFN-alpha(2b), which had an effect comparable to standard high-dose interferon-alpha(2b) but with less toxicity.     

Preflucel®: a Vero-cell culture-derived trivalent influenza vaccine

Vaccination is the principal means to reduce the impact of influenza infection. Effective vaccination programs require a reliable and safe production system. Traditionally, influenza vaccines are produced in embryonated chicken eggs. Over the last two decades, new cell culture-derived vaccines have been licensed and manufactured, and other vaccines are still in various phases of development. Vero cells have been used for the development of a wide variety of vaccines including influenza vaccines. Pandemic and avian influenza vaccines derived from Vero cells have been shown to be well tolerated and immunogenic in animal and Phase I-II clinical studies. A Phase III randomized, double-blind, placebo-controlled trial of a trivalent influenza vaccine produced in Vero-cell culture was conducted in 7250 adults aged 18-49 years. Overall protective efficacy for antigenically matched influenza vaccine was 78.5%. The vaccine was well tolerated with no treatment-related serious adverse events and compared favorably with egg-derived vaccines from previous trials. Vero-cell-derived influenza vaccines have the potential to be an important parts of the influenza vaccine strategy, especially if an avian-derived strain becomes predominant or the demand outstrips the capacity of egg-based production systems.