scholarly journals What Constitutes Protective Immunity Following Yellow Fever Vaccination?

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 671
Author(s):  
Jolynne Mokaya ◽  
Derick Kimathi ◽  
Teresa Lambe ◽  
George M. Warimwe
Keyword(s):  
Immune Responses ◽  
Yellow Fever ◽  
Protective Immunity ◽  
Effective Vaccine ◽  
Published Data ◽  
Cell Mediated Immunity ◽  
Dosing Regimens ◽  
Antibody Titers ◽  
Tropical Areas ◽  
Yellow Fever Vaccination

Yellow fever (YF) remains a threat to global health, with an increasing number of major outbreaks in the tropical areas of the world over the recent past. In light of this, the Eliminate Yellow Fever Epidemics Strategy was established with the aim of protecting one billion people at risk of YF through vaccination by the year 2026. The current YF vaccine gives excellent protection, but its use is limited by shortages in supply due to the difficulties in producing the vaccine. There are good grounds for believing that alternative fractional dosing regimens can produce strong protection and overcome the problem of supply shortages as less vaccine is required per person. However, immune responses to these vaccination approaches are yet to be fully understood. In addition, published data on immune responses following YF vaccination have mostly quantified neutralising antibody titers. However, vaccine-induced antibodies can confer immunity through other antibody effector functions beyond neutralisation, and an effective vaccine is also likely to induce strong and persistent memory T cell responses. This review highlights the gaps in knowledge in the characterisation of YF vaccine-induced protective immunity in the absence or presence of neutralising antibodies. The assessment of biophysical antibody characteristics and cell-mediated immunity following YF vaccination could help provide a comprehensive landscape of YF vaccine-induced immunity and a better understanding of correlates of protective immunity.

scholarly journals A Universal Dengue Vaccine Elicits Neutralizing Antibodies Against Strains from All Four Dengue Serotypes

2020 ◽  
Author(s):  
Naoko Uno ◽  
Ted M. Ross
Keyword(s):  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Rhesus Macaques ◽  
Effective Vaccine ◽  
Wild Type ◽  
Monovalent Vaccine ◽  
Viral Particles ◽  
Tropical Areas

Any potential dengue virus (DENV) vaccine needs to elicit protective immunity against strains from all four serotypes to avoid potential antibody dependent enhancement (ADE). In this study, four independent DENV envelope (E) glycoproteins were generated using wild-type E sequences from viruses isolated between 1943 to 2006 using computationally-optimized broadly reactive antigen (COBRA) methodology. COBRA and wild-type E antigens were expressed on the surface of subvirion viral particles (SVPs). Four separate wild-type E antigens were used for each serotype. Mice vaccinated with wild-type DENV SVPs had anti-E IgG antibodies that neutralized serotype specific viruses. COBRA DENV SVPs elicited a broader breadth of antibodies that neutralized strains across all four serotypes. Two COBRA DENV vaccine candidates that elicited the broadest breadth of neutralizing antibodies in mice were used to vaccinate rhesus macaques (Macca mulata) that were either immunologically naïve to any DENV serotype or were had pre-existing antibodies to DENV. Antibodies elicited by COBRA DENV E immunogens neutralized all 12 strains of DENV in vitro, which was comparable to antibodies elicited by a tetravalent wild-type E SVP vaccination mixture. Therefore, using a single DENV COBRA E protein can elicit neutralizing antibodies against strains representing all four serotypes of DENV in both naïve and dengue pre-immune populations. Importance Dengue virus infects millions of people living in the tropical areas of the world. Dengue induced diseases can range from mild to severe with death. An effective vaccine will need to neutralize viruses from all four serotypes of dengue without induced enhanced disease. A dengue E vaccine candidate generated by computationally optimized broadly reactive antigen algorithms elicits broadly neutralizing protection for current circulating strains from all four serotypes regardless of immune status. Most Dengue vaccines in development formulate four separate components based on prM-E from a wild type strain representing each serotype. Designing a monovalent vaccine that elicits protective immunity against all four serotypes is an effective and economical strategy

Characterization of main cytokine sources from the innate and adaptive immune responses following primary 17DD yellow fever vaccination in adults

Vaccine ◽  
2011 ◽  
Vol 29 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Maria Luiza Silva ◽  
Marina Angela Martins ◽  
Luçandra Ramos Espírito-Santo ◽  
Ana Carolina Campi-Azevedo ◽  
Denise Silveira-Lemos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yellow Fever ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Yellow Fever Vaccination

scholarly journals Oral Immunization with a Salmonella typhimurium Vaccine Vector Expressing Recombinant Enterotoxigenic Escherichia coli K99 Fimbriae Elicits Elevated Antibody Titers for Protective Immunity

1998 ◽  
Vol 66 (11) ◽  
pp. 5470-5476 ◽  
Author(s):  
Miguel A. Ascón ◽  
David M. Hone ◽  
Nancy Walters ◽  
David W. Pascual
Keyword(s):  
Escherichia Coli ◽  
Salmonella Typhimurium ◽  
Protective Immunity ◽  
Mononuclear Cells ◽  
Immunoglobulin A ◽  
Oral Immunization ◽  
Enterotoxigenic Escherichia Coli ◽  
Effective Vaccine ◽  
Antibody Titers ◽  
And Control

ABSTRACT Bovine enterotoxigenic Escherichia coli (ETEC) continues to cause mortality in piglets and newborn calves. In an effort to develop a safe and effective vaccine for the prevention of F5+ ETEC infections, a balanced lethalasd + plasmid carrying the complete K99 operon was constructed and designated pMAK99-asd +. Introduction of this plasmid into an attenuated Salmonella typhimurium Δaro Δasd strain, H683, resulted in strain AP112, which stably expresses E. coli K99 fimbriae. A single oral immunization of BALB/c and CD-1 mice with strain AP112 elicited significant mucosal immunoglobulin A (IgA) titers that remained elevated for >11 weeks. IgA and IgG responses in serum specific for K99 fimbriae were also induced, with a prominent IgG1, as well as IgG2a and IgG2b, titer. To assess the derivation of these antibodies, a K99 isotype-specific B-cell ELISPOT analysis was conducted by using mononuclear cells from the lamina propria of the small intestines (LP), Peyer’s patches (PP), and spleens of vaccinated and control BALB/c mice. This analysis revealed elevated numbers of K99 fimbria-specific IgA-producing cells in the LP, PP, and spleen, whereas elevated K99 fimbria-specific IgG-producing cells were detected only in the PP and spleen. These antibodies were important for protective immunity. One-day-old neonates from dams orally immunized with AP112 were provided passive protection against oral challenge with wild-type ETEC, in contrast to challenged neonates from unvaccinated dams or from dams vaccinated with a control Salmonella vector. These results confirm that oral Salmonella vaccine vectors effectively deliver K99 fimbriae to mucosal inductive sites for sustained elevation of IgA and IgG antibodies and for eliciting protective immunity.

scholarly journals Restricted replication and lysosomal trafficking of yellow fever 17D vaccine virus in human dendritic cells

2007 ◽  
Vol 88 (1) ◽  
pp. 148-156 ◽  
Author(s):  
Dupeh R. Palmer ◽  
Stefan Fernandez ◽  
John Bisbing ◽  
Kristina K. Peachman ◽  
Mangala Rao ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Yellow Fever ◽  
Virus Replication ◽  
Yellow Fever Virus ◽  
Vaccine Virus ◽  
Yellow Fever Vaccine ◽  
Effective Vaccine ◽  
Contributing Factors

The yellow fever virus attenuated 17D vaccine strain is a safe and effective vaccine and a valuable model system for evaluating immune responses against attenuated viral variants. This study compared the in vitro interactions of the commercially available yellow fever vaccine (YF-VAX), Dengue virus and the live-attenuated dengue vaccine PDK50 with dendritic cells (DCs), the main antigen-presenting cells at the initiation of immune responses. Similar to PDK50, infection with YF-VAX generated activated DCs; however, for YF-VAX, activation occurred with limited intracellular virus replication. The majority of internalized virus co-localized with endolysosomal markers within 90 min, suggesting that YF-VAX is processed rapidly in DCs. These results indicate that restricted virus replication and lysosomal compartmentalization may be important contributing factors to the success of the YF-VAX vaccine.

scholarly journals Evaluation of Lsa46 and Lsa77 Leptospiral Proteins for Their Immunoprotective Activities in Hamster Model of Leptospirosis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Aline F. Teixeira ◽  
Luis G. V. Fernandes ◽  
Antonio Souza Filho ◽  
Gisele O. Souza ◽  
Silvio A. Vasconcellos ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Protective Immunity ◽  
Effective Vaccine ◽  
Neglected Tropical Disease ◽  
Bacterial Burden ◽  
Hamster Model ◽  
Vaccine Candidates ◽  
Sterilizing Immunity

Leptospirosis is a neglected tropical disease caused by pathogenicLeptospiraspp. The lack of an effective vaccine favors the increase of the disease. Currently, surface-exposed proteins are the main targets for the search of vaccine candidates. In this study, we examined whether the surface Lsa46 and Lsa77 proteins, previously identified as laminin and plasminogen binding proteins, have the capacity of inducing protection and sterilizing immunity against challenge with virulentLeptospirain hamster model. Animals were subcutaneously immunized with Lsa46, Lsa77, or a combination of both in Alum adjuvant and challenged intraperitoneally withL. interrogansserovar Kennewicki strain Pomona Fromm. Hamster immunization with Lsa46 or Lsa77 or both promoted a strong IgG response. Th2- and Th1-biased immune responses were observed when Lsa46 and Lsa77 were individually administered, respectively, as detected by the IgG1/IgG2/3 ratio. Immunized hamsters with the combined proteins induced a Th1-biased immune response. Although the immunization with Lsa46 and Lsa77 stimulated protective immunity with reduction of bacterial burden, when compared to animals individually immunized with the proteins, the data was not statistically significant. Thus, although promising, more studies are needed before the role of these proteins in stimulating sterilizing immunity in mammals is conclusively determined.

scholarly journals Despite egg-adaptive mutations, the 2012-13 H3N2 influenza vaccine induced comparable antibody titers to the intended strain

2017 ◽  
Author(s):  
Sarah Cobey ◽  
Kaela Parkhouse ◽  
Benjamin S. Chambers ◽  
Hildegund C. Ertl ◽  
Kenneth E. Schmader ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Strain ◽  
Protective Immunity ◽  
Adaptive Mutations ◽  
Before And After ◽  
Antibody Titers ◽  
H3n2 Influenza ◽  
Subtype A ◽  
Protection Against Infection ◽  
Actual Vaccine

AbstractBackgroundInfluenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A/H3N2. Failure to achieve consistently high VE has been attributed both to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in 2012-13 was attributed to egg-adaptive mutations that created antigenic mismatch between the intended (A/Victoria/361/2011) and actual vaccine strain (IVR-165).MethodsWe investigate the basis of the low VE in 2012-2013 by evaluating whether vaccinated and unvaccinated individuals were infected by different viral strains and assessing the serologic responses to A/Victoria/361/2011 and the IVR-165 vaccine strain in an adult cohort before and after vaccination.ResultsWe found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 as much as to IVR-165. These results are consistent with the hypothesis that vaccination served merely to boost preexisting cross-reactive immune responses, which provided limited protection against infection with the circulating influenza strains.ConclusionsIn contrast to suggestive analyses based on ferret antisera, low H3N2 VE in 2012-13 does not appear to be due to the failure of the egg-adapted strain to induce a response to the intended vaccine strain. Instead, low VE might have been caused by the emergence of anti-genically novel influenza strains and low vaccine immunogenicity in a subset of the population.

scholarly journals Yellow fever vaccination immune responses are measurable up to 38 years after vaccination

2014 ◽  
Vol 21 ◽  
pp. 437
Author(s):  
R.W. Wieten ◽  
E. Jonker ◽  
G. de Bree ◽  
A. Goorhuis ◽  
L.G. Visser ◽  
...  
Keyword(s):  
Immune Responses ◽  
Yellow Fever ◽  
Yellow Fever Vaccination

Yellow fever

2011 ◽  
Author(s):  
Thomas P. Monath ◽  
J. Erin Staples
Keyword(s):  
Aedes Aegypti ◽  
Yellow Fever ◽  
Prevention And Control ◽  
Pacific Region ◽  
Tree Hole ◽  
The Pacific ◽  
Tropical Areas ◽  
Yellow Fever Vaccination ◽  
And Control ◽  
Flavivirus Infection

Yellow fever is an acute mosquito-borne flavivirus infection characterized in its full-blown form by fever, jaundice, albuminuria, and haemorrhage. Two forms are distinguished: urban yellow fever in which the virus is spread from person to person by peridomestic Aedes aegypti mosquitoes and jungle (sylvan) yellow fever transmitted by tree-hole breeding mosquitoes between non-human primates and sometimes humans. Yellow fever is endemic and epidemic in tropical areas of the Americas and Africa but has never appeared in Asia or the Pacific region. Prevention and control are effected principally through yellow fever vaccination.

scholarly journals Listeria monocytogenes-Induced Cell Death Inhibits the Generation of Cell-Mediated Immunity

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Erin Theisen ◽  
John-Demian Sauer
Keyword(s):  
T Cells ◽  
Cell Death ◽  
Listeria Monocytogenes ◽  
Immune Responses ◽  
Protective Immunity ◽  
Cell Mediated Immunity ◽  
Content Type ◽  
Cell Death Pathways ◽  
Host Cell Death ◽  
Inflammatory Milieu

ABSTRACT The influence of cell death on adaptive immunity has been studied for decades. Despite these efforts, the intricacies of how various cell death pathways shape immune responses in the context of infection remain unclear, particularly with regard to more recently discovered pathways such as pyroptosis. The emergence of Listeria monocytogenes as a promising immunotherapeutic platform demands a thorough understanding of how cell death induced in the context of infection influences the generation of CD8+ T-cell-mediated immune responses. To begin to address this question, we designed strains of L. monocytogenes that robustly activate necrosis, apoptosis, or pyroptosis. We hypothesized that proinflammatory cell death such as necrosis would be proimmunogenic while apoptosis would be detrimental, as has previously been reported in the context of sterile cell death. Surprisingly, we found that the activation of any host cell death in the context of L. monocytogenes infection inhibited the generation of protective immunity and specifically the activation of antigen-specific CD8+ T cells. Importantly, the mechanism of attenuation was unique for each type of cell death, ranging from deficits in costimulation in the context of necrosis to a suboptimal inflammatory milieu in the case of pyroptosis. Our results suggest that cell death in the context of infection is different from sterile-environment-induced cell death and that inhibition of cell death or its downstream consequences is necessary for developing effective cell-mediated immune responses using L. monocytogenes-based immunotherapeutic platforms.

scholarly journals Virus-Like Particle Vaccine Induces Protective Immunity against Homologous and Heterologous Strains of Influenza Virus

2007 ◽  
Vol 81 (7) ◽  
pp. 3514-3524 ◽  
Author(s):  
Fu-Shi Quan ◽  
Chunzi Huang ◽  
Richard W. Compans ◽  
Sang-Moo Kang
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
High Serum ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Lethal Challenge ◽  
Virus Challenge ◽  
Vaccine Approach

ABSTRACT Recurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated. In this study, we developed VLPs containing influenza virus A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung proinflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers and neutralizing activity against PR8 and A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no proinflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months postimmunization. Influenza VLPs induced mucosal immunoglobulin G and cellular immune responses, which were reactivated rapidly upon virus challenge. Long-lived antibody-secreting cells were detected in the bone marrow of immunized mice. Immune sera administered intranasally were able to confer 100% protection from a lethal challenge with PR8 or WSN, which provides further evidence that anti-HA antibodies are primarily responsible for preventing infection. Taken together, these results indicate that nonreplicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.

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