Zika Virus Vaccine Development: Progress in the Face of New Challenges

2019 ◽  
Vol 70 (1) ◽  
pp. 121-135 ◽  
Author(s):  
Michael S. Diamond ◽  
Julie E. Ledgerwood ◽  
Theodore C. Pierson
Keyword(s):  
Zika Virus ◽  
Vaccine Development ◽  
Global Level ◽  
Rapid Progress ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Public Health Infrastructure ◽  
Health Infrastructure ◽  
The Face ◽  
Disease Analysis

Zika virus (ZIKV) emerged at a global level when it spread to the Americas and began causing congenital malformations and microcephaly in 2015. A rapid response by academia, government, public health infrastructure, and industry has enabled the expedited development and testing of a suite of vaccine platforms aiming to control and eliminate ZIKV-induced disease. Analysis of key immunization and pathogenesis studies in multiple animal models, including during pregnancy, has begun to define immune correlates of protection. Nonetheless, the deployment of ZIKV vaccines, along with the confirmation of their safety and efficacy, still has major challenges, one of which is related to the waning of the epidemic. In this review, we discuss the measures that enabled rapid progress and highlight the path forward for successful deployment of ZIKV vaccines.

Epilogue

2016 ◽  
pp. 119-122
Author(s):  
Christian W. McMillen
Keyword(s):  
Public Health ◽  
Climate Change ◽  
Lessons Learned ◽  
The Past ◽  
Public Health Infrastructure ◽  
Health Infrastructure ◽  
The World ◽  
The Future ◽  
The Face ◽  
New Challenges

There will be more pandemics. A pandemic might come from an old, familiar foe such as influenza or might emerge from a new source—a zoonosis that makes its way into humans, perhaps. The epilogue asks how the world will confront pandemics in the future. It is likely that patterns established long ago will re-emerge. But how will new challenges, like climate change, affect future pandemics and our ability to respond? Will lessons learned from the past help with plans for the future? One thing is clear: in the face of a serious pandemic much of the developing world’s public health infrastructure will be woefully overburdened. This must be addressed.

scholarly journals Role of Opsonophagocytosis in Immune Protection against Malaria

Vaccines ◽  
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.

scholarly journals Human Cytomegalovirus Congenital (cCMV) Infection Following Primary and Nonprimary Maternal Infection: Perspectives of Prevention through Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 194
Author(s):  
Giuseppe Gerna ◽  
Daniele Lilleri
Keyword(s):  
Human Cytomegalovirus ◽  
Subunit Vaccine ◽  
Vaccine Development ◽  
Maternal Infection ◽  
Major Step ◽  
Congenital Cytomegalovirus ◽  
Partial Protection ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Hyperimmune Globulin

Congenital cytomegalovirus (cCMV) might occur as a result of the human cytomegalovirus (HCMV) primary (PI) or nonprimary infection (NPI) in pregnant women. Immune correlates of protection against cCMV have been partly identified only for PI. Following either PI or NPI, HCMV strains undergo latency. From a diagnostic standpoint, while the serological criteria for the diagnosis of PI are well-established, those for the diagnosis of NPI are still incomplete. Thus far, a recombinant gB subunit vaccine has provided the best results in terms of partial protection. This partial efficacy was hypothetically attributed to the post-fusion instead of the pre-fusion conformation of the gB present in the vaccine. Future efforts should be addressed to verify whether a new recombinant gB pre-fusion vaccine would provide better results in terms of prevention of both PI and NPI. It is still a matter of debate whether human hyperimmune globulin are able to protect from HCMV vertical transmission. In conclusion, the development of an HCMV vaccine that would prevent a significant portion of PI would be a major step forward in the development of a vaccine for both PI and NPI.

scholarly journals Passive immunisation of convalescent human anti-Zika plasma protects against challenge with New World Zika virus in cynomolgus macaques

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Neil Berry ◽  
Sarah Kempster ◽  
Claire Ham ◽  
Adrian Jenkins ◽  
Jo Hall ◽  
...  
Keyword(s):  
Zika Virus ◽  
Vaccine Development ◽  
De Novo ◽  
Protective Efficacy ◽  
Lymphoid Tissues ◽  
Passive Immunisation ◽  
Post Challenge ◽  
Virus Challenge ◽  
Immune Correlates ◽  
Cynomolgus Macaques

Abstract Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

scholarly journals Cellular and Humoral Immunity Protect against Vaginal Zika Virus Infection in Mice

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Jason M. Scott ◽  
Tania J. Lebratti ◽  
Justin M. Richner ◽  
Xiaoping Jiang ◽  
Estefania Fernandez ◽  
...  
Keyword(s):  
T Cells ◽  
Pregnant Women ◽  
Zika Virus ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Female Reproductive Tract ◽  
Mosquito Vector ◽  
Zikv Infection ◽  
Correlates Of Protection ◽  
Immune Correlates

ABSTRACTZika virus (ZIKV), which can cause devastating disease in fetuses of infected pregnant women, can be transmitted by mosquito inoculation and sexual routes. Little is known about immune protection against sexually transmitted ZIKV. In this study, we show that previous infection through intravaginal or subcutaneous routes with a contemporary Brazilian strain of ZIKV can protect against subsequent intravaginal challenge with a homologous strain. Both routes of inoculation induced high titers of ZIKV-specific and neutralizing antibody in serum and the vaginal lumen. Virus-specific T cells were recruited to and retained in the female reproductive tract after intravaginal and subcutaneous ZIKV infection. Studies in mice with genetic or acquired deficiencies in B and/or T cells demonstrated that both lymphocyte populations redundantly protect against intravaginal challenge in ZIKV-immune animals. Passive transfer of ZIKV-immune IgG or T cells significantly limited intravaginal infection of naive mice, although antibody more effectively prevented dissemination throughout the reproductive tract. Collectively, our experiments begin to establish the immune correlates of protection against intravaginal ZIKV infection, which should inform vaccination strategies in nonpregnant and pregnant women.IMPORTANCEThe recent ZIKV epidemic resulted in devastating outcomes in fetuses and may affect reproductive health. Unlike other flaviviruses, ZIKV can be spread by sexual contact as well as a mosquito vector. While previous studies have identified correlates of protection for mosquito-mediated infection, few have focused on immunity against sexual transmission. As exposure to ZIKV via mosquito bite has likely occurred to many living in areas where ZIKV is endemic, our study addresses whether this route of infection can protect against subsequent sexual exposure. We demonstrate that subcutaneous ZIKV infection can protect against subsequent vaginal infection by generating both local antiviral T cell and antibody responses. Our research begins to define the immune correlates of protection for ZIKV infection in the vagina and provides a foundation for testing ZIKV vaccines against sexual transmission.

scholarly journals Neutralization Fingerprinting Technology for Characterizing Polyclonal Antibody Responses to Dengue Vaccines

2021 ◽  
Author(s):  
Nagarajan Raju ◽  
Xiaoyan Zhan ◽  
Subash Das ◽  
Lovkesh Karwal ◽  
Hansi J. Dean ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Dengue Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Modeling Framework ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Tetravalent Vaccine ◽  
Antibody Specificities

AbstractDengue is a major public health threat. There are four serotypes of dengue virus (DENV), therefore efforts are focused on development of safe and effective tetravalent DENV vaccines. While neutralizing antibodies contribute to protective immunity, there are still important gaps in understanding of immune responses elicited by dengue infection and vaccination, including defining immune correlates of protection. To that end, here we present a computational modeling framework for evaluating the specificities of neutralizing antibodies elicited to tetravalent DENV vaccines, based on the concept of antibody-virus neutralization fingerprints. We developed and applied this framework to samples from clinical studies of TAK-003, a tetravalent vaccine candidate currently in phase 3 trials, to characterize the effect of prior dengue infection (baseline) on the specificities of vaccine-elicited antibody responses. Our results suggested a similarity of neutralizing antibody specificities in baseline-seronegative individuals. In contrast, amplification of pre-existing neutralizing antibody specificities was predicted for baseline-seropositive individuals, thus quantifying the role of immunologic imprinting in driving antibody responses to DENV vaccines. The analysis framework proposed here can apply to studies of sequential dengue infections and other tetravalent DENV vaccines and can contribute to understanding dengue immune correlates of protection to help guide further vaccine development and optimization.

scholarly journals Advancing Our Understanding of Protective Maternal Immunity as a Guide for Development of Vaccines To Reduce Congenital Cytomegalovirus Infections

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Sallie R. Permar ◽  
Mark R. Schleiss ◽  
Stanley A. Plotkin
Keyword(s):  
Public Health ◽  
Vaccine Development ◽  
Fetal Loss ◽  
Natural Immunity ◽  
Maternal Immunity ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Health Goal ◽  
Pharmaceutical Manufacturers ◽  
Public Health Goal

ABSTRACTHuman cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. Congenital HCMV (cCMV) infection is a major global contributor to long-term neurologic deficits, including deafness, microcephaly, and neurodevelopmental delay, as well as to fetal loss and occasional infant mortality. Accordingly, design of a maternal vaccine to prevent cCMV continues to be a top public health priority. Nevertheless, we remain without a licensed vaccine. Maternal immunity provides partial protection, as the risk of vertical HCMV transmission from chronically infected mothers is reduced compared to settings in which the mother is newly infected during pregnancy. Therefore, an understanding of the maternal immune correlates of protection against cCMV is critical to informing design of an efficacious maternal vaccine. Although vaccine development is being assiduously pursued by a large number of pharmaceutical manufacturers, biotechnology organizations, and academic researchers, some pessimism has been expressed regarding the issue of whether a vaccine to protect against cCMV is possible. This pessimism is based on observations that natural immunity is not completely protective against maternal reinfection and congenital transmission. However, we assert that optimism regarding vaccine development is indeed justified, on the basis of accruing evidence of immune correlates of protection—readily achievable by vaccination—that are associated with reduced transmission of HCMV to the fetus in seronegative women. In light of the substantial burden on society conferred by cCMV infection, even a modest reduction in the occurrence of this fetal disease is an important public health goal and justifies aggressive clinical evaluation of vaccines currently in the pipeline.

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