Immune correlates for dengue vaccine development

Zoonotic transmission of orthohantaviruses from rodent reservoirs to humans has been the cause of severe fatalities. Human infections are reported worldwide, but vaccines have been approved only in China and Korea. Orthohantavirus vaccine development has been pursued with no sense of urgency due to the relative paucity of cases in countries outside China and Korea. However, the orthohantaviruses continuously evolve in hosts and thus the current vaccine may not work as well against some variants. Therefore, a more effective vaccine should be prepared against the orthohantaviruses. In this review, we discuss the issues caused by the orthohantavirus vaccine. Given the pros and cons of the orthohantavirus vaccine, we suggest strategies for the development of better vaccines in terms of pandemic preparedness.

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A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00588-2 ◽

2021 ◽

Author(s):

Vincent Legros ◽

Solène Denolly ◽

Manon Vogrig ◽

Bertrand Boson ◽

Eglantine Siret ◽

...

Keyword(s):

Intensive Care ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Surface Protein ◽

Humoral Response ◽

Neutralizing Antibody ◽

Rapid Decline ◽

Serum Samples ◽

Immune Correlates ◽

Human Coronaviruses

AbstractUnderstanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

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Analysis of cell-mediated immune responses in support of dengue vaccine development efforts

Vaccine ◽

10.1016/j.vaccine.2015.09.104 ◽

2015 ◽

Vol 33 (50) ◽

pp. 7083-7090 ◽

Cited By ~ 10

Author(s):

Alan L. Rothman ◽

Jeffrey R. Currier ◽

Heather L. Friberg ◽

Anuja Mathew

Keyword(s):

Immune Responses ◽

Vaccine Development ◽

Dengue Vaccine

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Overview of Plant-Derived Vaccine Antigens: Dengue Virus

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3401k ◽

2011 ◽

Vol 14 (3) ◽

pp. 400 ◽

Cited By ~ 7

Author(s):

Ravindra B Malabadi ◽

Advaita Ganguly ◽

Jaime A Teixeira da Silva ◽

Archana Parashar ◽

Mavanur R Suresh ◽

...

Keyword(s):

Infectious Diseases ◽

Dengue Virus ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Low Cost ◽

Current Status ◽

Human Immune Deficiency Virus ◽

Dengue Vaccine ◽

New Methods ◽

Vaccine Antigens

ABSTRACT - This review highlights the advantages and current status of plant-derived vaccine development with special reference to the dengue virus. There are numerous problems involved in dengue vaccine development, and there is no vaccine against all four dengue serotypes. Dengue vaccine development using traditional approaches has not been satisfactory in terms of inducing neutralizing antibodies. Recently, these issues were addressed by showing a very good response to inducing neutralizing antibodies by plant-derived dengue vaccine antigens. This indicates the feasibility of using plant-derived vaccine antigens as a low-cost method to combat dengue and other infectious diseases. The application of new methods and strategies such as dendritic cell targeting in cancer therapy, severe acute respiratory syndrome, tuberculosis, human immune deficiency virus, and malaria might play an important role. These new methods are more efficient than traditional protocols. It is expected that in the near future, plant-derived vaccine antigens or antibodies will play an important role in the control of human infectious diseases. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes

Clinical and Vaccine Immunology ◽

10.1128/cvi.00330-06 ◽

2006 ◽

Vol 14 (2) ◽

pp. 182-189 ◽

Cited By ~ 32

Author(s):

David H. Holman ◽

Danher Wang ◽

Kanakatte Raviprakash ◽

Nicholas U. Raja ◽

Min Luo ◽

...

Keyword(s):

Immune Responses ◽

Dengue Virus ◽

Vaccine Development ◽

De Novo ◽

Natural Infection ◽

Hemorrhagic Fever ◽

Virus Infections ◽

Dengue Vaccine ◽

Membrane Antigens ◽

Dengue Virus Serotypes

ABSTRACT Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

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Progress and challenges in TB vaccine development

F1000Research ◽

10.12688/f1000research.13588.1 ◽

2018 ◽

Vol 7 ◽

pp. 199 ◽

Cited By ~ 51

Author(s):

Gerald Voss ◽

Danilo Casimiro ◽

Olivier Neyrolles ◽

Ann Williams ◽

Stefan H.E. Kaufmann ◽

...

Keyword(s):

Clinical Trials ◽

Vaccine Development ◽

Scientific Progress ◽

Human Infection ◽

Experimental Medicine ◽

Vaccine Platform ◽

Vaccine Candidates ◽

Clinical Endpoints ◽

Immune Correlates ◽

Efficacy Trials

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development. To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models. However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

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Dengue vaccine development: Global and Indian scenarios

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2019.01.029 ◽

2019 ◽

Vol 84 ◽

pp. S80-S86 ◽

Cited By ~ 8

Author(s):

Sathyamangalam Swaminathan ◽

Navin Khanna

Keyword(s):

Vaccine Development ◽

Dengue Vaccine

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Role of Opsonophagocytosis in Immune Protection against Malaria

Vaccines ◽

10.3390/vaccines8020264 ◽

2020 ◽

Vol 8 (2) ◽

pp. 264

Author(s):

Wolfgang W. Leitner ◽

Megan Haraway ◽

Tony Pierson ◽

Elke S. Bergmann-Leitner

Keyword(s):

Protective Immunity ◽

Defense Mechanisms ◽

Vaccine Development ◽

Immune Defense ◽

Complement Components ◽

Correlates Of Protection ◽

Immune Correlates ◽

Antibody Titers ◽

Simple Measurement ◽

Humoral Responses

The quest for immune correlates of protection continues to slow vaccine development. To date, only vaccine-induced antibodies have been confirmed as direct immune correlates of protection against a plethora of pathogens. Vaccine immunologists, however, have learned through extensive characterizations of humoral responses that the quantitative assessment of antibody responses alone often fails to correlate with protective immunity or vaccine efficacy. Despite these limitations, the simple measurement of post-vaccination antibody titers remains the most widely used approaches for vaccine evaluation. Developing and performing functional assays to assess the biological activity of pathogen-specific responses continues to gain momentum; integrating serological assessments with functional data will ultimately result in the identification of mechanisms that contribute to protective immunity and will guide vaccine development. One of these functional readouts is phagocytosis of antigenic material tagged by immune molecules such as antibodies and/or complement components. This review summarizes our current understanding of how phagocytosis contributes to immune defense against pathogens, the pathways involved, and defense mechanisms that pathogens have evolved to deal with the threat of phagocytic removal and destruction of pathogens.

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