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 Development of an Aotus nancymaae Model for Shigella Vaccine Immunogenicity and Efficacy Studies

2014 ◽  
Vol 82 (5) ◽  
pp. 2027-2036 ◽  
Author(s):  
Michael Gregory ◽  
Robert W. Kaminski ◽  
Luis A. Lugo-Roman ◽  
Hugo Galvez Carrillo ◽  
Drake Hamilton Tilley ◽  
...  
Keyword(s):  
Vaccine Strain ◽  
Attack Rate ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Shigella Flexneri ◽  
Content Type ◽  
Immune Correlates ◽  
Study Results ◽  
Combination Vaccines ◽  
Series Of Experiments

ABSTRACTSeveral animal models exist to evaluate the immunogenicity and protective efficacy of candidateShigellavaccines. The two most widely used nonprimate models for vaccine development include a murine pulmonary challenge model and a guinea pig keratoconjunctivitis model. Nonhuman primate models exhibit clinical features and gross and microscopic colonic lesions that mimic those induced in human shigellosis. Challenge models for enterotoxigenicEscherichia coli(ETEC) andCampylobacterspp. have been successfully developed withAotus nancymaae, and the addition of aShigella-Aotuschallenge model would facilitate the testing of combination vaccines. A series of experiments were designed to identify the dose ofShigella flexneri2a strain 2457T that induces an attack rate of 75% in theAotusmonkey. After primary challenge, the dose required to induce an attack rate of 75% was calculated to be 1 × 1011CFU.Shigella-specific immune responses were low after primary challenge and subsequently boosted upon rechallenge. However, preexisting immunity derived from the primary challenge was insufficient to protect against the homologousShigellaserotype. A successive study inA. nancymaaeevaluated the ability of multiple oral immunizations with live-attenuatedShigellavaccine strain SC602 to protect against challenge. After three oral immunizations, animals were challenged withS. flexneri2a 2457T. A 70% attack rate was demonstrated in control animals, whereas animals immunized with vaccine strain SC602 were protected from challenge (efficacy of 80%;P= 0.05). The overall study results indicate that theShigella-Aotus nancymaaechallenge model may be a valuable tool for evaluating vaccine efficacy and investigating immune correlates of protection.

scholarly journals Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys

Science ◽  
2016 ◽  
Vol 353 (6304) ◽  
pp. 1129-1132 ◽  
Author(s):  
P. Abbink ◽  
R. A. Larocca ◽  
R. A. De La Barrera ◽  
C. A. Bricault ◽  
E. T. Moseley ◽  
...  
Keyword(s):  
Zika Virus ◽  
Rhesus Monkeys ◽  
Protective Efficacy ◽  
Virus Challenge

scholarly journals Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy

2005 ◽  
Vol 79 (5) ◽  
pp. 2666-2677 ◽  
Author(s):  
Jodi K. Craigo ◽  
Feng Li ◽  
Jonathan D. Steckbeck ◽  
Shannon Durkin ◽  
Laryssa Howe ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Equine Infectious Anemia Virus ◽  
Protective Efficacy ◽  
Accessory Gene ◽  
Live Attenuated Vaccine ◽  
Virus Challenge ◽  
Proviral Clone ◽  
Immune Correlates ◽  
Equine Infectious Anemia ◽  
Anemia Virus

ABSTRACT Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine efficacy, we examine here the relationship between the extent of virus attenuation, the maturation of host immune responses, and vaccine efficacy in a comparative study of three related attenuated EIAV proviral vaccine strains: the previously described EIAVUKΔS2 derived from a virulent proviral clone, EIAVUKΔS2/DU containing a second gene mutation in the virulent proviral clone, and EIAVPRΔS2 derived from a reference avirulent proviral clone. Inoculations of parallel groups of eight horses resulted in relatively low levels of viral replication (average of 102 to 103 RNA copies/ml) and a similar maturation of EIAV envelope-specific antibody responses as determined in quantitative and qualitative serological assays. However, experimental challenge of the experimentally immunized horses by our standard virulent EIAVPV strain by using a low-dose multiple exposure protocol (three inoculations with 10 median horse infective doses, administered intravenously) revealed a marked difference in the protective efficacy of the various attenuated proviral vaccine strains that was evidently associated with the extent of vaccine virus attenuation, time of viral challenge, and the apparent maturation of virus-specific immunity.

scholarly journals Protective Efficacy of Nucleic Acid Vaccines Against Transmission of Zika Virus During Pregnancy in Mice

2019 ◽  
Vol 220 (10) ◽  
pp. 1577-1588 ◽  
Author(s):  
Brett W Jagger ◽  
Kimberly A Dowd ◽  
Rita E Chen ◽  
Pritesh Desai ◽  
Bryant Foreman ◽  
...  
Keyword(s):  
Zika Virus ◽  
Messenger Rna ◽  
Plasma Cells ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Congenital Infection ◽  
Comparable Efficacy ◽  
Small Subset ◽  
Type I ◽  
Fetal Head

Abstract Zika virus (ZIKV) caused an epidemic of congenital malformations in 2015–2016. Although many vaccine candidates have been generated, few have demonstrated efficacy against congenital ZIKV infection. Here, we evaluated lipid-encapsulated messenger RNA (mRNA) vaccines and a DNA plasmid vaccine encoding the prM-E genes of ZIKV in mouse models of congenital infection. Although the DNA vaccine provided comparable efficacy against vertical transmission of ZIKV, the mRNA vaccines, including one that minimizes antibody-dependent enhancement of infection, elicited higher levels of antigen-specific long-lived plasma cells and memory B cells. Despite the induction of robust neutralizing antibody titers by all vaccines, breakthrough seeding of the placenta and fetal head was observed in a small subset of type I interferon signaling–deficient immunocompromised dams. In comparison, evaluation of one of the mRNA vaccines in a human STAT2-knockin transgenic immunocompetent mouse showed complete protection against congenital ZIKV transmission. These data will inform ongoing human ZIKV vaccine development efforts and enhance our understanding of the correlates of vaccine-induced protection.

scholarly journals Influence of Respiratory Syncytial Virus F Glycoprotein Conformation on Induction of Protective Immune Responses

2016 ◽  
Vol 90 (11) ◽  
pp. 5485-5498 ◽  
Author(s):  
Concepción Palomo ◽  
Vicente Mas ◽  
Michelle Thom ◽  
Mónica Vázquez ◽  
Olga Cano ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Membrane Fusion ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Viral Fusion ◽  
Virus Challenge ◽  
Advantages And Disadvantages ◽  
Syncytial Virus

ABSTRACTHuman respiratory syncytial virus (hRSV) vaccine development has received new impetus from structure-based studies of its main protective antigen, the fusion (F) glycoprotein. Three soluble forms of F have been described: monomeric, trimeric prefusion, and trimeric postfusion. Most human neutralizing antibodies recognize epitopes found exclusively in prefusion F. Although prefusion F induces higher levels of neutralizing antibodies than does postfusion F, postfusion F can also induce protection against virus challenge in animals. However, the immunogenicity and protective efficacy of the three forms of F have not hitherto been directly compared. Hence, BALB/c mice were immunized with a single dose of the three proteins adjuvanted with CpG and challenged 4 weeks later with virus. Serum antibodies, lung virus titers, weight loss, and pulmonary pathology were evaluated after challenge. Whereas small amounts of postfusion F were sufficient to protect mice, larger amounts of monomeric and prefusion F proteins were required for protection. However, postfusion and monomeric F proteins were associated with more pathology after challenge than was prefusion F. Antibodies induced by all doses of prefusion F, in contrast to other F protein forms, reacted predominantly with the prefusion F conformation. At high doses, prefusion F also induced the highest titers of neutralizing antibodies, and all mice were protected, yet at low doses of the immunogen, these antibodies neutralized virus poorly, and mice were not protected. These findings should be considered when developing new hRSV vaccine candidates.IMPORTANCEProtection against hRSV infection is afforded mainly by neutralizing antibodies, which recognize mostly epitopes found exclusively in the viral fusion (F) glycoprotein trimer, folded in its prefusion conformation, i.e., before activation for membrane fusion. Although prefusion F is able to induce high levels of neutralizing antibodies, highly stable postfusion F (found after membrane fusion) is also able to induce neutralizing antibodies and protect against infection. In addition, a monomeric form of hRSV F that shares epitopes with prefusion F was recently reported. Since each of the indicated forms of hRSV F may have advantages and disadvantages for the development of safe and efficacious subunit vaccines, a direct comparison of the immunogenic properties and protective efficacies of the different forms of hRSV F was made in a mouse model. The results obtained show important differences between the noted immunogens that should be borne in mind when considering the development of hRSV vaccines.

scholarly journals Protective efficacy of rhesus adenovirus COVID-19 vaccines against mouse-adapted SARS-CoV-2

2021 ◽  
Author(s):  
Lisa Tostanoski ◽  
Lisa Gralinski ◽  
David Martinez ◽  
Alexandra Schaefer ◽  
Shant Mahrokhian ◽  
...  
Keyword(s):  
Viral Replication ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Rapid Development ◽  
Model Systems ◽  
Wild Type ◽  
Challenge Virus ◽  
Vaccine Candidates ◽  
Immune Correlates ◽  
Adenovirus Vectors

The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice.

scholarly journals Early embryonic loss following intravaginal Zika virus challenge in rhesus macaques

2021 ◽  
Author(s):  
Christina M Newman ◽  
Alice F. Tarantal ◽  
Michele L. Martinez ◽  
Heather A Simmons ◽  
Terry K Morgan ◽  
...  
Keyword(s):  
Gestational Age ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Sexual Transmission ◽  
First Trimester ◽  
Sample Collection ◽  
Post Challenge ◽  
Virus Challenge ◽  
Adverse Pregnancy ◽  
Low Passage

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted by Aedes species mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 x 10^7 PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (~30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found to have nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (~155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.

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.

scholarly journals Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques

2021 ◽  
Vol 12 ◽  
Author(s):  
Christina M. Newman ◽  
Alice F. Tarantal ◽  
Michele L. Martinez ◽  
Heather A. Simmons ◽  
Terry K. Morgan ◽  
...  
Keyword(s):  
Gestational Age ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
Sexual Transmission ◽  
First Trimester ◽  
Sample Collection ◽  
Post Challenge ◽  
Virus Challenge ◽  
Adverse Pregnancy ◽  
Low Passage

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted by Aedes species mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 x 107 PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (~30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found with nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (~155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.

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