scholarly journals Adjuvants: Classification,Modus Operandi, and Licensing

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Juliana de Souza Apostólico ◽  
Victória Alves Santos Lunardelli ◽  
Fernanda Caroline Coirada ◽  
Silvia Beatriz Boscardin ◽  
Daniela Santoro Rosa
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Immune Responses ◽  
Protective Immunity ◽  
Mechanisms Of Action ◽  
Clinical Settings ◽  
Modus Operandi ◽  
Subunit Vaccines ◽  
Correlates Of Protection ◽  
In The Beginning

Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.

scholarly journals Vaccinology in the era of high-throughput biology

2015 ◽  
Vol 370 (1671) ◽  
pp. 20140146 ◽  
Author(s):  
Helder I. Nakaya ◽  
Bali Pulendran
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
High Throughput ◽  
Protective Immunity ◽  
Molecular Signatures ◽  
Correlates Of Protection ◽  
Recent Advances ◽  
Induced Immunity ◽  
Experimental Challenge ◽  
Lack Of Knowledge

Vaccination has been tremendously successful saving lives and preventing infections. However, the development of vaccines against global pandemics such as HIV, malaria and tuberculosis has been obstructed by several challenges. A major challenge is the lack of knowledge about the correlates and mechanisms of protective immunity. Recent advances in the application of systems biological approaches to analyse immune responses to vaccination in humans are beginning to yield new insights about mechanisms of vaccine immunity, and to define molecular signatures, induced rapidly after vaccination, that correlate with and predict vaccine induced immunity. Here, we review these advances and discuss the potential of this systems vaccinology approach in defining novel correlates of protection in clinical trials, and in infection-induced ‘experimental challenge models' in humans.

Immune system changes and immunosenescence

2017 ◽  
pp. 331-336
Author(s):  
Graham Pawelec ◽  
Ludmila Müller ◽  
Tamas Fülöp ◽  
Deborah Dunn-Walters
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Older People ◽  
Protective Immunity ◽  
Elderly Population ◽  
Immune Status ◽  
The Elderly ◽  
Degenerative Diseases ◽  
System Changes ◽  
Increased Susceptibility

The immune system defends against infection, but older people paradoxically suffer not only from failing immunity resulting in increased susceptibility to infections and decreased responsiveness to vaccination, but at the same time increased inflammation and immunopathology accompanying immune responses. Interventions to reduce such deleterious effects while enhancing protective immunity are challenging but need to be confronted if we are to deal successfully with the increasing numbers of elderly and frail people in modern societies. To do this, we need to understand the mechanisms responsible for age-associated increased susceptibility to infections and immune-influenced chronic degenerative diseases of ageing. Defining relevant age-associated alterations and identifying reliable biomarkers for monitoring clinically-relevant immune status in the elderly population is crucial to overcoming these problems. Here, we briefly outline age-associated changes to immunity collectively termed ‘immunosenescence’.

scholarly journals Yersinia pestis caf1 Variants and the Limits of Plague Vaccine Protection

2008 ◽  
Vol 76 (5) ◽  
pp. 2025-2036 ◽  
Author(s):  
Lauriane E. Quenee ◽  
Claire A. Cornelius ◽  
Nancy A. Ciletti ◽  
Derek Elli ◽  
Olaf Schneewind
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Protective Immunity ◽  
Wild Type ◽  
Vaccine Protection ◽  
Subunit Vaccines ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Plague Vaccine ◽  
Highly Virulent

ABSTRACT Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

scholarly journals Shigella -Specific Immune Profiles Induced after Parenteral Immunization or Oral Challenge with Either Shigella flexneri 2a or Shigella sonnei

mSphere ◽  
2021 ◽  
Author(s):  
Kristen A. Clarkson ◽  
Chad K. Porter ◽  
Kawsar R. Talaat ◽  
Robert W. Frenck ◽  
Cristina Alaimo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Shigella Flexneri ◽  
Severe Disease ◽  
Oral Challenge ◽  
Immune Markers ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Shigella Flexneri 2A ◽  
Parenteral Immunization

Although immune correlates of protection have yet to be defined for shigellosis, prior studies have demonstrated that Shigella infection provides protection against reinfection in a serotype-specific manner. Therefore, it is likely that subjects with moderate to severe disease post-oral challenge would be protected from a homologous rechallenge, and investigating immune responses in these subjects may help identify immune markers associated with the development of protective immunity.

scholarly journals A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease

2020 ◽  
Author(s):  
Angkana T. Huang ◽  
Bernardo Garcia-Carreras ◽  
Matt D.T. Hitchings ◽  
Bingyi Yang ◽  
Leah Katzelnick ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Scientific Literature ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Future Research ◽  
Critical Determinant ◽  
Severity Of Disease ◽  
Correlates Of Protection ◽  
Antibody Kinetics

The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.

scholarly journals Identification of Surrogates and Correlates of Protection in Protective Immunity againstMycobacterium bovisInfection Induced in Neonatal Calves by Vaccination withM. bovisBCG Pasteur andM. bovisBCG Danish

2011 ◽  
Vol 18 (3) ◽  
pp. 373-379 ◽  
Author(s):  
J. C. Hope ◽  
M. L. Thom ◽  
M. McAulay ◽  
E. Mead ◽  
H. M. Vordermeier ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Significant Degree ◽  
Degree Of Protection ◽  
Correlates Of Protection ◽  
Ifn Γ ◽  
Neonatal Calves ◽  
Protection Against Infection

ABSTRACTVaccination of neonatal calves withMycobacterium bovisbacillus Calmette-Guérin (BCG) induces a significant degree of protection against infection with virulentM. bovis, the causative agent of bovine tuberculosis (bTB). We compared two strains of BCG, Pasteur and Danish, in order to confirm that the current European human vaccine strain (BCG Danish) induced protective immunity in calves, and we assessed immune responses to determine correlates of protection that could assist future vaccine evaluation in cattle. Both vaccine strains induced antigen (purified protein derivate [PPD])-specific gamma interferon (IFN-γ) in whole-blood cultures. These responses were not significantly different for BCG Pasteur and BCG Danish and peaked at week 2 to 4 postvaccination. Vaccination with either BCG Danish or BCG Pasteur induced significant protection against bTB, with reductions in both lesion score and bacteriological burden evident in both groups of vaccinated calves compared with nonvaccinated control calves. Measurement of IFN-γ-expressing T lymphocytes postvaccination and postchallenge revealed both correlates and surrogates of protective efficacy. The frequency of central memory T lymphocytes present at 12 weeks postvaccination (at the time ofM. bovischallenge) correlated significantly with protection. Conversely, the number of IFN-γ-expressing effector T cells present afterM. bovischallenge was correlated with disease. These results demonstrate that vaccination of neonatal calves with either BCG Pasteur or BCG Danish induces protective immune responses against TB. In addition, we show that measurement of antigen-specific T lymphocyte populations may provide a reliable means for identifying protective vaccine candidates.

Traditional Medicines, HIV, and Related Infections

2011 ◽  
Vol 23 (1) ◽  
pp. 159-164 ◽  
Author(s):  
M. Patel ◽  
P. Bessong ◽  
H. Liu
Keyword(s):  
Clinical Trials ◽  
Immune System ◽  
Ethical Issues ◽  
Mechanisms Of Action ◽  
Antiretroviral Drugs ◽  
In Vivo Studies ◽  
Traditional Medicines ◽  
Anti Hiv

Traditional medicines are an integral part of health care worldwide, even though their efficacy has not been scientifically proven. HIV-infected individuals may use them singularly or in combination with conventional medicines. Many in vitro studies have proven the anti-HIV, anti- Candida, and anti–herpes simplex virus potential of traditional plants and identified some of the mechanisms of action. Very few in vivo studies are available that involve a small number of participants and show controversial results. In addition, knowledge is limited of the role of traditional medicines in the enhancement of the immune system. The use of traditional medicines with antiretroviral drugs (ARVs) has created a problem because drug interactions compromise the efficacy of ARVs. Several currently popular plants have been studied in the laboratory for their interaction with ARVs, with disadvantageous results. Unfortunately, no clinical trials are available. The science of traditional medicines is relatively new and is at present being modernized worldwide. However, there are still ethical issues regarding traditional medicines that need to be addressed—for example, regulations regarding quality control and standardization of medicines, regulation and education of healers who deliver these medicines, and unregulated clinical trials. The workshop addressed the following questions about traditional medicine and their use in HIV infection: What are the mechanisms of action of anti-HIV traditional medicines? Should traditional medicines be used in conjunction with ARV? Do traditional medicines enhance the immune system? Should medicinal plants be used for the control of oral infections associated with HIV? What are the ethical issues surrounding the use of traditional medicines for the treatment of HIV and associated infections?

scholarly journals Correlates of Protection Induced by Vaccination

2010 ◽  
Vol 17 (7) ◽  
pp. 1055-1065 ◽  
Author(s):  
Stanley A. Plotkin
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Current Knowledge ◽  
Immune Memory ◽  
Effector Memory ◽  
Intracellular Pathogens ◽  
Protective Response ◽  
Correlates Of Protection ◽  
Highly Correlated ◽  
Almost All

ABSTRACT This paper attempts to summarize current knowledge about immune responses to vaccines that correlate with protection. Although the immune system is redundant, almost all current vaccines work through antibodies in serum or on mucosa that block infection or bacteremia/viremia and thus provide a correlate of protection. The functional characteristics of antibodies, as well as quantity, are important. Antibody may be highly correlated with protection or synergistic with other functions. Immune memory is a critical correlate: effector memory for short-incubation diseases and central memory for long-incubation diseases. Cellular immunity acts to kill or suppress intracellular pathogens and may also synergize with antibody. For some vaccines, we have no true correlates, but only useful surrogates, for an unknown protective response.

scholarly journals Protective Immunity and Reduced Renal Colonization Induced by Vaccines Containing Recombinant Leptospira interrogans Outer Membrane Proteins and Flagellin Adjuvant

2015 ◽  
Vol 22 (8) ◽  
pp. 965-973 ◽  
Author(s):  
D. Monaris ◽  
M. E. Sbrogio-Almeida ◽  
C. C. Dib ◽  
T. A. Canhamero ◽  
G. O. Souza ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Immune Responses ◽  
Outer Membrane ◽  
Protective Immunity ◽  
Outer Membrane Proteins ◽  
Protein A ◽  
Leptospira Interrogans ◽  
Renal Tubules ◽  
Subunit Vaccines ◽  
Content Type

ABSTRACTLeptospirosis is a global zoonotic disease caused by differentLeptospiraspecies, such asLeptospira interrogans, that colonize the renal tubules of wild and domestic animals. Thus far, attempts to develop effective leptospirosis vaccines, both for humans and animals, have failed to induce immune responses capable of conferring protection and simultaneously preventing renal colonization. In this study, we evaluated the protective immunity induced by subunit vaccines containing seven different recombinantLeptospira interrogansouter membrane proteins, including the carboxy-terminal portion of the immunoglobulinlike protein A (LigAC) and six novel antigens, combined with aluminum hydroxide (alum) orSalmonellaflagellin (FliC) as adjuvants. Hamsters vaccinated with the different formulations elicited high antigen-specific antibody titers. Immunization with LigAC, either with alum or flagellin, conferred protective immunity but did not prevent renal colonization. Similarly, animals immunized with LigACor LigACcoadministered with six leptospiral proteins with alum adjuvant conferred protection but did not reduce renal colonization. In contrast, immunizing animals with the pool of seven antigens in combination with flagellin conferred protection and significantly reduced renal colonization by the pathogen. The present study emphasizes the relevance of antigen composition and added adjuvant in the efficacy of antileptospirosis subunit vaccines and shows the complex relationship between immune responses and renal colonization by the pathogen.

scholarly journals A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Angkana T. Huang ◽  
Bernardo Garcia-Carreras ◽  
Matt D. T. Hitchings ◽  
Bingyi Yang ◽  
Leah C. Katzelnick ◽  
...  
Keyword(s):  
Public Health ◽  
Systematic Review ◽  
Immune Responses ◽  
Protective Immunity ◽  
Scientific Literature ◽  
Cross Reactivity ◽  
Future Research ◽  
Correlates Of Protection ◽  
Human Coronaviruses ◽  
Antibody Kinetics

Abstract Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARS-CoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV, MERS-CoV and endemic human coronaviruses (HCoVs). We reviewed 2,452 abstracts and identified 491 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While further studies of SARS-CoV-2 are necessary to determine immune responses, evidence from other coronaviruses can provide clues and guide future research.

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