Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR) of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1). When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05) neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01). Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05). Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.

Impact of vaccines given during pregnancy on the offspring of women consulting a travel clinic: a longitudinal study

BACKGROUND: Little is known on the impact of travel vaccinations during pregnancy on child outcomes, in particular on the long-term psychomotor development. The objectives of the study were (1) to estimate the rate of premature births, congenital abnormalities, and mental and physical development problems of children born from mothers who had been vaccinated during pregnancy and (2) to compare these rates with those of children whose mothers had not been vaccinated during pregnancy. METHODS: Longitudinal study including (1) retrospectively pregnant women having attended our travel clinic before (vaccinated) and (2) prospectively mothers attending our clinic (nonvaccinated). We performed phone interviews with mothers vaccinated during pregnancy, up to 10 years before, and face-to-face interviews with nonvaccinated age-matched mothers, ie, women attending the travel clinic who had one child of about the same age as the one of the case to compare child development between both groups. RESULTS: Fifty-three women vaccinated during pregnancy were interviewed as well as 53 nonvaccinated ones. Twenty-eight (53%) women received their vaccination during the first trimester. The most frequent vaccine administered was hepatitis A (55% of the cases), followed by di-Te (34%), IM poliomyelitis (23%), yellow fever (12%), A-C meningitis (8%), IM typhoid (4%), and oral poliomyelitis (4%). Children were followed for a range of 1 to 10 years. Rates of premature births were 5.7% in both groups; congenital abnormalities were 1.9% in the vaccinated cohort versus 5.7% in the nonvaccinated one; children took their first steps at a median age of 12 months in both cohorts; among schoolchildren, 5% of the vaccinated cohort versus 7.7% of the nonvaccinated attended a lower level or a specialized school. CONCLUSION: In this small sample size, there was no indication that usual travel vaccinations, including the yellow fever one, had deleterious effect on child outcome and development

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias.

Background: Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods: A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and prehospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results: Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93). Conclusion: Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

VaxcineTM: an oil-based adjuvant for influenza vaccines

Vaccination is the method of choice for the prevention of influenza infection. However, the quantity of the antigen available, especially in the case of pandemics, often fails to meet the global demand. However, improved adjuvants can overcome this problem. Preliminary results obtained in this study revealed that one year after a single subcutaneous immunisation with influenza A H3N2 virus in an oil-based carrier, VaxcineTM, outbreed mice produced a high immunoglobulin G response that lasted for up to one year and exhibited less variation in titre compared with the response of the control group treated with alum. The haemagglutination-inhibition titres induced by VaxcineTM were also higher than those generated by alum. These data indicate that VaxcineTM is a good adjuvant candidate for seasonal influenza vaccines.

Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America

Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America.

Reaching for the Holy Grail: insights from infection/cure models on the prospects for vaccines for Trypanosoma cruziinfection

Prevention of Trypanosoma cruzi infection in mammals likely depends on either prevention of the invading trypomastigotes from infecting host cells or the rapid recognition and killing of the newly infected cells byT. cruzi-specific T cells. We show here that multiple rounds of infection and cure (by drug therapy) fails to protect mice from reinfection, despite the generation of potent T cell responses. This disappointing result is similar to that obtained with many other vaccine protocols used in attempts to protect animals from T. cruziinfection. We have previously shown that immune recognition ofT. cruziinfection is significantly delayed both at the systemic level and at the level of the infected host cell. The systemic delay appears to be the result of a stealth infection process that fails to trigger substantial innate recognition mechanisms while the delay at the cellular level is related to the immunodominance of highly variable gene family proteins, in particular those of the trans-sialidase family. Here we discuss how these previous studies and the new findings herein impact our thoughts on the potential of prophylactic vaccination to serve a productive role in the prevention of T. cruziinfection and Chagas disease.

A randomised double-blind clinical trial of two yellow fever vaccines prepared with substrains 17DD and 17D-213/77 in children nine-23 months old

This randomised, double-blind, multicentre study with children nine-23 months old evaluated the immunogenicity of yellow fever (YF) vaccines prepared with substrains 17DD and 17D-213/77. YF antibodies were tittered before and 30 or more days after vaccination. Seropositivity and seroconversion were analysed according to the maternal serological status and the collaborating centre. A total of 1,966 children were randomised in the municipalities of the states of Mato Grosso do Sul, Minas Gerais and São Paulo and blood samples were collected from 1,714 mothers. Seropositivity was observed in 78.6% of mothers and 8.9% of children before vaccination. After vaccination, seropositivity rates of 81.9% and 83.2%, seroconversion rates of 84.8% and 85.8% and rates of a four-fold increase over the pre-vaccination titre of 77.6% and 81.8% were observed in the 17D-213/77 and 17DD subgroups, respectively. There was no association with maternal immunity. Among children aged 12 months or older, the seroconversion rates of 69% were associated with concomitant vaccination against measles, mumps and rubella. The data were not conclusive regarding the interference of maternal immunity in the immune response to the YF vaccine, but they suggest interference from other vaccines. The failures in seroconversion after vaccination support the recommendation of a booster dose in children within 10 years of the first dose.

New insights on the development of fungal vaccines: from immunity to recent challenges

Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

Melanoma vaccines

Many vaccines have been very successful. They can protect from many different infectious diseases, and thus contribute enormously to public health. The majority of successful vaccines induce neutralizing antibodies, which are essential for protection from disease, by the inhibition of microbe invasion and spread through the body, via extracellular compartments, or by neutralization of toxins. In contrast to infectious diseases, the pathological process in cancer is primarily intracellular. Immunity to cancer depends mainly on T cells which are capable of identifying and eliminating abnormal cells, via recognition of peptide antigens presented by major histocompatibility complex molecules at the cell surface. In some instances, tumor-specific antibodies can contribute to immune defense against cancer. Unfortunately, for many solid tumors (including melanoma), this mechanism is insufficient. Nevertheless, the search for cancer-neutralizing antibodies continues, similar to, e.g., HIV neutralizing antibodies. In this chapter, we focus on the development of T cell vaccines, a great challenge but also a promising approach as a new therapy for melanoma, other cancers, and intracellular pathogens

Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells.

Immunotherapy of melanoma is aimed to mobilize cytolytic CD8+ T cells playing a central role in protective immunity. Despite numerous clinical vaccine trials, only few patients exhibited strong antigen-specific T-cell activation, stressing the need to improve vaccine strategies. For a rational development, we propose to focus on molecularly defined vaccine components, and evaluate their immunogenicity with highly reproducible and standardized methods for ex vivo immune monitoring. Careful immunogenicity comparison of vaccine formulations in phase I/II studies allow to select optimized vaccines for subsequent clinical efficacy testing in large scale phase III trials.

Modern Vaccines/Adjuvants Formulation-Session 2 (Plenary II): May 15-17, 2013-Lausanne, Switzerland.

On the 15-17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies.

Malaria vaccines - The long synthetic peptide approach: Technical and conceptual advancements.

This review describes the advances in malaria antigen discovery and vaccine development using the long synthetic peptide platforms that have been made available during the past 5 years. The most recent technical developments regarding peptide synthesis with the optimized production of large synthetic fragments are discussed. Clinical trials of long synthetic peptides are also reviewed. These trials demonstrated that long synthetic peptides are safe and immunogenic when formulated with various adjuvants. In addition, long synthetic peptides can elicit an antibody response in humans and have demonstrated inhibitory activity against parasite growth in vitro. Finally, new approaches to exploit the abundance of genomic data and the flexibility and speed of peptide synthesis are proposed.