Use Of Adjuvants In Vaccines Research Articles

Studies about polymers, their interactions with the immune system and applications in immunotechnology in Uruguay: a systematic review / Estudos sobre polímeros, suas interações com o sistema imunológico e aplicações em imunotecnologia no Uruguai: uma revisão sistemática

The aim of the present work was to review, for the first time, articles published by researchers from Uruguay describing the effect of polymers on the vertebrate immune system or the use of polymers in immunotechnology. Databases and the national registry were searched. The first articles included were published in 1993. Several groups of articles were defined for better understanding: 1) polymeric molecules from parasites and pathogenic bacteria; 2) studies on the use of polymers with adjuvant properties; 3) use of synthetic polymers in immunotechnology development and 4) use of polymers in drug delivery systems targeting the immune system. Various approaches have been explored for applications related to animal and human health. Examples include the identification of molecules suitable as antigens for vaccines and the use of adjuvants in vaccines. Immunoassays for the detection and quantification of antibodies or antigens and a cancer therapy system have been identified.

Commonly Used Adjuvant Human Vaccines: Advantages and Side Effects

Vaccines are a cost-effective and successful means for preventing disease. Routine health vaccine administration begins in early childhood and extends into the elderly; however, there is evidence to suggest that the immunologic and protective response to vaccination is less potent in older individuals. In recent years, newer adjuvant vaccines have been developed to improve humoral and cell-mediated immune response after vaccination. Despite the use of adjuvants in vaccines for many decades, there is limited teaching in postgraduate medical education regarding the adjuvants found in human vaccines. We summarize the current literature cited in PubMed from January 1980 to December 2019. Studies examined included those supporting the use of adjuvants in human vaccines, the mechanisms via which they enhance the immunologic response, and the reported side effects that are associated with the use of adjuvant vaccines. Overall, the data show that newer adjuvant vaccines lead to improved humoral and cell-mediated immunity against infections in populations, including those with decreased response to typical vaccines without adjuvants. Side effects related to adjuvants in vaccines were reported. Research aimed at improving vaccine effectiveness and minimizing side effects continues to be underway.

Relapse of polymyalgia rheumatica following adjuvanted influenza vaccine: A case-based review.

Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatological condition affecting individuals aged >50 years. There have been rare reports of PMR and other vasculitides developing within 3 months of influenza vaccination. Influenza is a major public health issue associated with seasonal increased mortality and intensified health care service use. Annual vaccination is the most effective intervention to prevent influenza, especially in elderly individuals. We report a severe "flare" of PMR in a 70-year-old patient after receiving the adjuvanted trivalent influenza vaccine, as recommended by the Joint Committee on Vaccination and Immunisations for this age group in the UK National Health Service in 2018-2019. The adverse event (AE) could be interpreted as the newly described autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome) as both PMR and ASIA display hyperactive immune responses. Caution is warranted in the use of vaccine adjuvants in patients with PMR with pre-existing imbalance of B and T cell homeostasis. Rare AEs are important to individuals, and personalized medicine means we should move away from "one size fits all" for vaccines, as well as for therapeutics.

Hepatitis B Vaccination and Waning Hepatitis B Immunity in Persons Living with HIV.

Persons with HIV are at a higher risk for acquiring HBV (hepatitis B virus) than the general population due to shared modes of transmission and are significantly more likely to develop and die from sequelae of chronic HBV infection. Early vaccination is key to achieving HBV protective immunity, but response rates are still much lower than in the general population, ranging from 35 to 70%. Individuals with HIV also experience more rapidly waning immunity than those without HIV. Strategies to augment initial response and improve long-term immunity in individuals with HIV include alterations in dose, frequency, and the use of immune adjuvants. Recent studies have focused on the use of different vaccine formulations, the use of vaccine adjuvants, increased number and strength of vaccine dosages, increased dose frequency, alternative routes of administration, dual vaccinations, and the use of booster vaccines. Although no consensus has been reached on the use of certain vaccination regimens, three and four double-dose vaccine schedules via the intramuscular route have demonstrated higher initial response rates. Early vaccination when CD4 cell counts are greater than 350/mm3 with low viral loads has been shown to improve initial response, along with completion of immunization series. Adjuvants such as TLR4 and TLR9 agonists appear to improve response to HBV vaccination, but further research is needed in individuals with HIV. Persons with HIV have significant lower initial and long-term seroresponse rates after HBV vaccination than immunocompetent individuals. Recent and ongoing studies continue to evaluate multiple strategies to improve these rates within a uniquely susceptible population.

Nanoparticle vaccines against viral infections.

Despite numerous efforts, we still do not have prophylactic vaccines for many clinically relevant viruses, such as HIV, hepatitis C virus, Zika virus, and respiratory syncytial virus. Several factors have contributed to the current lack of effective vaccines, including the high rate of viral mutation, low immunogenicity of recombinant viral antigens, instability of viral antigenic proteins administered in vivo, sophisticated mechanisms of viral immune evasion, and inefficient induction of mucosal immunity by vaccine models studied to date. Some of these obstacles could be partially overcome by the use of vaccine adjuvants. Nanoparticles have been intensively investigated as vaccine adjuvants because they possess chemical and structural properties that improve immunogenicity. The use of nanotechnology in the construction of immunization systems has developed into the field of viral nanovaccinology. The purpose of this paper is to review and correlate recent discoveries concerning nanoparticles and specific properties that contribute to the immunogenicity of viral nanoparticle vaccines, bio-nano interaction, design of nanoparticle vaccines for clinically relevant viruses, and future prospects for viral nanoparticle vaccination.

Pattern recognition receptor agonists enhance protection elicited by a single, low dose protein vaccine in an immunization route-specific manner

Abstract Despite advances to increase vaccine efficacy, influenza A virus (IAV) remains a significant health risk. Current vaccines against IAV rely on the generation of strain specific antibodies that fail to provide protection against heterosubtypic IAV. Vaccination may be improved through the use of vaccine adjuvants to amplify antigen presenting cell (APC) activation and enhance T and B cell priming. Combined adjuvants that trigger multiple pattern recognition receptors (PRR) are a promising strategy to better mimic live infection. In this study, the efficacy of combining CpG and MPLA, which activate TLR9 and TLR4 respectively, as vaccine adjuvants was examined. It was observed that single, low dose hemagglutinin (HA) protein vaccines containing combination CpG and MPLA delivered intramuscularly (i.m.) or intranasally (i.n.) elicit superior protection against lethal challenge compared to vaccines containing single agonists, as indicated by lower mortality and significantly lower morbidity. Early systemic cytokine responses are being investigated to elucidate the mechanism behind this improved vaccine efficacy. However, it was observed that i.m. administration of combination agonist vaccines induced higher IgG2c antibody responses compared to single agonist vaccines, while minimal levels of antibodies were observed in mice vaccinated i.n. In addition, T cell analysis following lethal infection indicated that i.n. vaccination induces distinct activation profiles compared to i.m. Taken together a comparison of the antibody and T cell profiles of mice vaccinated i.m. and i.n with combined TLR9 and TLR4 agonists suggests that route of vaccination can dictate immune response and may modify effective correlates of protection.

Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses.

The development of vaccines inducing efficient CD8(+) T cell responses is the focus of intense research. Dendritic cells (DCs) expressing the XCR1 chemokine receptor, also known as CD103(+) or CD8α(+) DCs, excel in the presentation of extracellular Ags to CD8(+) T cells. Because of its high numbers of DCs, including XCR1(+) DCs, the skin dermis is an attractive site for vaccine administration. By creating laser-generated micropores through the epidermis, we targeted a model protein Ag fused to XCL1, the ligand of XCR1, to dermal XCR1(+) DCs and induced Ag-specific CD8(+) and CD4(+) T cell responses. Efficient immunization required the emigration of XCR1(+) dermal DCs to draining lymph nodes and occurred irrespective of TLR signaling. Moreover, a single intradermal immunization protected mice against melanoma tumor growth in prophylactic and therapeutic settings, in the absence of exogenous adjuvant. The mild inflammatory milieu created in the dermis by skin laser microporation itself most likely favored the development of potent T cell responses in the absence of exogenous adjuvants. The existence of functionally equivalent XCR1(+) dermal DCs in humans should permit the translation of laser-assisted intradermal delivery of a tumor-specific vaccine targeting XCR1(+) DCs to human cancer immunotherapy. Moreover, considering that the use of adjuvants in vaccines is often associated with safety issues, the possibility of inducing protective responses against melanoma tumor growth independently of the administration of exogenous adjuvants should facilitate the development of safer vaccines.

The Third International Congress on Controversies in Rheumatology & Autoimmunity (CORA)<br>Sorrento, 12–14 March 2015

The main idea of the CORA meetings is to present problems concerning the autoimmunity network. In Sorrento experts presented new and exploratory research and analysis on rheumatology, autoimmunity and clinical immunology. Lectures were held in the form of debates, and lecturers were asked to discuss subjects from different points of view. Numerous prominent scientists took part in the lectures and discussions, including Claudio Vitalii, Maurizo Cutulo, Joahim Sieper, Hector Chinoy, Ricard Cervera, Zoltan Szekanecz, Nancy Agmon-Levin and, last but not least, Yehuda Shoenfeld, one of the initiators and the host of this event. Of many topics arousing interest, the controversy surrounding the existence of the seronegative antiphospholipid syndrome led to a particularly lively discussion, as the audience witnessed a verbal duel between Guido Valesini and Vittorio Pengo. The problem of the use of adjuvants in vaccines and the development of ASIA syndrome still remains controversial. Professor Yehuda Shoenfeld pointed out that while vaccinations undoubtedly represent progress of humanity and their effectiveness in combating disease should not be undermined, there is a risk associated with the impact of adjuvants used in vaccines. He concluded that science should strive to create the best vaccines and new adjuvants. In oral presentations a lot of authors paid attention to new directions of immune-diagnostics. The reports of the search for new markers of RA were presented, pointing to the process of carbamoylation and the use of antibody assays for carbamoylated proteins. Carbamoylated proteins (CarP) could be early markers in rheumatoid arthritis and may have particular relevance for CCP negative patients. The poster sessions presented works of many research centers around the world. Poland was represented by both rheumatologists and cardiologists. The meeting took place in the unique setting of a picturesque Italian town with omnipresent lemon and orange trees. As the lecturers taking part in this event were experienced and recognized by the scientific world, performing sessions in the form of debates proved to be both interesting and involving for the audience. The participants will surely be encouraged to take part in further meetings conducted in the same form. The next CORA meeting is scheduled to take place in 2017 in Bologna.

Cell Recruitment and Cytokines in Skin Mice Sensitized with the Vaccine Adjuvants: Saponin, Incomplete Freund’s Adjuvant, and Monophosphoryl Lipid A

Vaccine adjuvants are substances associated with antigens that are fundamental to the formation of an intense, durable, and fast immune response. In this context, the use of vaccine adjuvants to generate an effective cellular immune response is crucial for the design and development of vaccines against visceral leishmaniasis. The objective of this study was to evaluate innate inflammatory response induced by the vaccine adjuvants saponin (SAP), incomplete Freund’s adjuvant (IFA), and monophosphoryl lipid A (MPL). After a single dose of adjuvant was injected into the skin of mice, we analyzed inflammatory reaction, selective cell migration, and cytokine production at the injection site, and inflammatory cell influx in the peripheral blood. We found that all vaccine adjuvants were able to promote cell recruitment to the site without tissue damage. In addition, they induced selective migration of neutrophils, macrophages, and lymphocytes. The influx of neutrophils was notable at 12 h in all groups, but at other time points it was most evident after inoculation with SAP. With regard to cytokines, the SAP led to production of interleukin (IL)-2, IL-6, and IL-4. IFA promoted production of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, IL-17, IL-4, and IL-10. We also observed that MPL induced high production of IL-2, TNF-α, and IFN-γ, in addition to IL-6, IL-17, and IL-10. In peripheral blood, values of certain cell populations in the local response changed after stimulation. Our data demonstrate that the three vaccine adjuvants stimulate the early events of innate immune response at the injection site, suggesting their ability to increase the immunogenicity of co-administered antigens. Moreover, this work provides relevant information about elements of innate and acquired immune response induced by vaccine adjuvants administered alone.

Intradermal influenza vaccine and new devices: a promising chance for vaccine improvement

Introduction: The main public health strategy for reducing the influenza burden is annual vaccination. However, because the immune response in the elderly and frail subjects is known to be less vigorous than in younger adults, novel strategies have been explored in the last decade to augment immune response after immunization. These have included an increased dosage, multiple dose vaccinations, use of vaccine adjuvants and more efficient routes of vaccine delivery.Areas covered: This review discusses recent advances in intradermally administered influenza vaccines with particular attention to immunogenicity and safety data from clinical trials performed using appropriate injection systems which, combining consistent injection depth and volume, safety, simplicity and ease-of-use, allowed large scale evaluation.Expert opinion: Substantial experience has been accumulated with Intanza 9 and Intanza 15 μg/IDflu 15 μg, administered using BD's Soluvia™ device, and are the first intradermal trivalent inactivated split-virion influenza vaccines to be licensed for use in 18 – 59 year adults and in elderly people, respectively. Clinical data showed that they are safe and immunogenic and can offer significant advantages in terms of higher acceptability, higher immunogenicity in the elderly and dose-sparing in adults younger than 60 years when compared with intramuscularly administered vaccine.

Interferons as potential adjuvants in prophylactic vaccines

Importance of the field: Vaccines are still one of the best approaches to manage infectious diseases. Despite the advances in drug therapies, prophylactic medicine is still more cost efficient and minimizes the burden in the heath system. Despite all the research in vaccine development, many infectious diseases are still without an effective vaccine. The use of adjuvants in vaccines has been one successful strategy to increase efficacy. IFNs are widely expressed cytokines that have potent antiviral effects. These cytokines are the first line of defense against viral infections and have important roles in immuno surveillance for malignant cells. One of the most promising uses of IFNs is as adjuvants that are co-applied with antigen in vaccines.Areas covered in this review: In this review, a cumulative analysis of many of the studies that have used IFN-α, -β, -γ and -λ as adjuvants between 1987 and the present suggests that many do possess the capacity to serve as potent immunoadjuvants for vaccination.What the reader will gain: This review provides a very large collection of studies involving all types of IFNs used as adjuvants in vaccines using different vaccination strategies and various animal models.Take home message: It is clear that the use of IFNs not only improved the efficacy and safety of most vaccines, but also had important immunomodulatory effect directing TH1 immune responses.

Influenza vaccine: The challenge of antigenic drift

Influenza continues to have a major worldwide impact, resulting in considerable human suffering and economic burden. The regular recurrence of influenza epidemics is thought to be caused by antigenic drift, and a number of studies have shown that sufficient changes can accumulate in the virus to allow influenza to reinfect the same host. To address this, influenza vaccine content is reviewed annually to ensure protection is maintained, despite the emergence of drift variants; however, it is not always possible to capture every significant drift, partly due to the timing of the recommendations. Vaccine mismatch can impact on vaccine effectiveness, and has significant epidemiological and economical consequences, as was seen most apparently in the 1997-1998 influenza season. To meet the challenge of antigenic drift, vaccines that confer broad protection against heterovariant strains are needed against seasonal, epidemic and pandemic influenza. In addition to the use of vaccine adjuvants, emerging research areas include development of a universal vaccine and the use of vaccines that exploit mechanisms of cross-protective immunity.

The development and use of vaccine adjuvants.

Interest in vaccine adjuvants is intense and growing, because many of the new subunit vaccine candidates lack sufficient immunogenicity to be clinically useful. In this review, I have emphasized modern vaccine adjuvants injected parenterally, or administered orally, intranasally, or transcutaneously with licensed or experimental vaccines in humans. Every adjuvant has a complex and often multi-factorial immunological mechanism, usually poorly understood in vivo. Many determinants of adjuvanticity exist, and each adjuvanted vaccine is unique. Adjuvant safety is critical and can enhance, retard, or stop development of an adjuvanted vaccine. The choice of an adjuvant often depends upon expensive experimental trial and error, upon cost, and upon commercial availability. Extensive regulatory and administrative support is required to conduct clinical trials of adjuvanted vaccines. Finally, comparative adjuvant trials where one antigen is formulated with different adjuvants and administered by a common protocol to animals and humans can accelerate vaccine development.