scholarly journals A single-shot Lassa vaccine induces long-term immunity and protects cynomolgus monkeys against heterologous strains

2021 ◽  
Vol 13 (597) ◽  
pp. eabf6348
Author(s):  
Mathieu Mateo ◽  
Stéphanie Reynard ◽  
Alexandra Journeaux ◽  
Clara Germain ◽  
Jimmy Hortion ◽  
...  
Keyword(s):  
Immune Responses ◽  
Virus Vaccine ◽  
Measles Virus ◽  
Lassa Virus ◽  
Single Shot ◽  
Virus Infections ◽  
Cynomolgus Monkeys ◽  
Western Africa ◽  
High Diversity

A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP). To evaluate vaccine efficacy against heterologous strains of Lassa virus, we challenged the monkeys a month later with heterologous strains from lineage II or lineage VII, finding that the vaccine was protective against these strains. A second cohort of monkeys was challenged 1 year later with the homologous Josiah strain, finding that a single dose of MeV-NP was sufficient to protect all vaccinated monkeys. These studies demonstrate that MeV-NP can generate both long-lasting immune responses and responses that are able to protect against diverse strains of Lassa virus.

Vaccines inducing immunity to Lassa virus glycoprotein and nucleoprotein protect macaques after a single shot

2019 ◽  
Vol 11 (512) ◽  
pp. eaaw3163 ◽  
Author(s):  
Mathieu Mateo ◽  
Stéphanie Reynard ◽  
Xavier Carnec ◽  
Alexandra Journeaux ◽  
Nicolas Baillet ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Measles Virus ◽  
Vaccine Candidate ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Single Shot ◽  
Efficacy Analysis ◽  
Western Africa ◽  
Efficacious Vaccine

Lassa fever is a major threat in Western Africa. The large number of people living at risk for this disease calls for the development of a vaccine against Lassa virus (LASV). We generated live-attenuated LASV vaccines based on measles virus and Mopeia virus platforms and expressing different LASV antigens, with the aim to develop a vaccine able to protect after a single shot. We compared the efficacy of these vaccines against LASV in cynomolgus monkeys. The vaccines were well tolerated and protected the animals from LASV infection and disease after a single immunization but with varying efficacy. Analysis of the immune responses showed that complete protection was associated with robust secondary T cell and antibody responses against LASV. Transcriptomic and proteomic analyses showed an early activation of innate immunity and T cell priming after immunization with the most effective vaccines, with changes detectable as early as 2 days after immunization. The most efficacious vaccine candidate, a measles vector simultaneously expressing LASV glycoprotein and nucleoprotein, has been selected for further clinical evaluation.

Long-Term Regulation of Interferon Production by Lymphocytes from Children Inoculated with Live Measles Virus Vaccine

1988 ◽  
Vol 158 (6) ◽  
pp. 1386-1390 ◽  
Author(s):  
T. Nakayama ◽  
T. Urano ◽  
M. Osano ◽  
N. Maehara ◽  
K. Sasaki ◽  
...  
Keyword(s):  
Virus Vaccine ◽  
Measles Virus ◽  
Interferon Production

scholarly journals MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

2022 ◽  
Author(s):  
Yeonsu Kim ◽  
Xiaoyan Zheng ◽  
Kathrin Eschke ◽  
M. Zeeshan Chaudhry ◽  
Federico Bertoglio ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Influenza A ◽  
High Morbidity ◽  
Single Shot ◽  
Respiratory Pathogens ◽  
Antigenic Peptides ◽  
Immune Protection ◽  
Vaccine Vectors

AbstractGlobal pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of severe acute respiratory syndrome coronavirus 2 (MCMVS). A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA-vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to the effects of memory T cells. Conclusively, we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

scholarly journals Early and Strong Immune Responses Are Associated with Control of Viral Replication and Recovery in Lassa Virus-Infected Cynomolgus Monkeys

2009 ◽  
Vol 83 (11) ◽  
pp. 5890-5903 ◽  
Author(s):  
Sylvain Baize ◽  
Philippe Marianneau ◽  
Philippe Loth ◽  
Stéphanie Reynard ◽  
Alexandra Journeaux ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Viral Replication ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mononuclear Cells ◽  
Type I Interferons ◽  
Lassa Virus ◽  
Type I ◽  
Cynomolgus Monkeys

ABSTRACT Lassa virus causes a hemorrhagic fever endemic in West Africa. The pathogenesis and the immune responses associated with the disease are poorly understood, and no vaccine is available. We followed virological, pathological, and immunological markers associated with fatal and nonfatal Lassa virus infection of cynomolgus monkeys. The clinical picture was characterized by fever, weight loss, depression, and acute respiratory syndrome. Transient thrombocytopenia and lymphopenia, lymphadenopathy, splenomegaly, infiltration of mononuclear cells, and alterations of the liver, lungs, and endothelia were observed. Survivors exhibited fewer lesions and a lower viral load than nonsurvivors. Although all animals developed strong humoral responses, antibodies appeared more rapidly in survivors and were directed against GP1, GP2, and NP. Type I interferons were detected early after infection in survivors but only during the terminal stages in fatalities. The mRNAs for CXCL10 (IP-10) and CXCL11 (I-TAC) were abundant in peripheral blood mononuclear cells and lymph nodes from infected animals, but plasma interleukin-6 was detected only in fatalities. In survivors, high activated-monocyte counts were followed by a rise in the total number of circulating monocytes. Activated T lymphocytes circulated in survivors, whereas T-cell activation was low and delayed in fatalities. In vitro stimulation with inactivated Lassa virus induced activation of T lymphocytes from all infected monkeys, but only lymphocytes from survivors proliferated. Thus, early and strong immune responses and control of viral replication were associated with recovery, whereas fatal infection was characterized by major alterations of the blood formula and, in organs, weak immune responses and uncontrolled viral replication.

Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children

Vaccine ◽  
2016 ◽  
Vol 34 (46) ◽  
pp. 5664-5669 ◽  
Author(s):  
Kulkanya Chokephaibulkit ◽  
Chukiat Sirivichayakul ◽  
Usa Thisyakorn ◽  
Chitsanu Pancharoen ◽  
Mark Boaz ◽  
...  
Keyword(s):  
Immune Responses ◽  
Japanese Encephalitis ◽  
Virus Vaccine ◽  
Chimeric Virus ◽  
Long Term Follow Up

Immune responses against measles virus in cynomolgus monkeys

2008 ◽  
Vol 31 (1) ◽  
pp. 25-35 ◽  
Author(s):  
Hiroki Sato ◽  
Fumio Kobune ◽  
Yasushi Ami ◽  
Misako Yoneda ◽  
Chieko Kai
Keyword(s):  
Immune Responses ◽  
Measles Virus ◽  
Cynomolgus Monkeys

scholarly journals MCMV based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

2021 ◽  
Author(s):  
Luka Cicin-Sain ◽  
Yeonsu Kim ◽  
Xiaoyan Zheng ◽  
Kathrin Eschke ◽  
M. Zeeshan Chaudhry ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Influenza A ◽  
Neutralizing Antibody ◽  
Single Shot ◽  
Respiratory Pathogens ◽  
Antigenic Peptides ◽  
Immune Protection ◽  
Vaccine Vectors

Abstract Global pandemics by influenza or coronaviruses cause severe disruptions to the public health and lead to severe morbidity and mortality. Vaccines against these pathogens remain a medical need. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses, where outstandingly large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing the hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of the severe acute respiratory syndrome coronavirus 2 (MCMVS). A single shot of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to effects of memory T cells. Conclusively, we show here that MCMV vectors do not only induce long-term cellular immunity, but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.

Long-Term Persistence of Antibody following Enders' Original and More Attenuated Live Measles Virus Vaccine

1976 ◽  
Vol 153 (3) ◽  
pp. 441-443 ◽  
Author(s):  
E. B. Buynak ◽  
R. E. Weibel ◽  
A. A. McLean ◽  
M. R. Hilleman
Keyword(s):  
Virus Vaccine ◽  
Measles Virus

Cellular immune responses during complicated and uncomplicated measles virus infections of man

1984 ◽  
Vol 31 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Robert L. Hirsch ◽  
Diane E. Griffin ◽  
Richard T. Johnson ◽  
Susan J. Cooper ◽  
Imelda Lindo de Soriano ◽  
...  
Keyword(s):  
Immune Responses ◽  
Measles Virus ◽  
Virus Infections ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Animal Models of Lassa Fever

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 197 ◽  
Author(s):  
Rachel A. Sattler ◽  
Slobodan Paessler ◽  
Hinh Ly ◽  
Cheng Huang
Keyword(s):  
Animal Model ◽  
Hearing Loss ◽  
Animal Models ◽  
Sensorineural Hearing Loss ◽  
Lassa Fever ◽  
Lassa Virus ◽  
Disease Pathogenesis ◽  
Western Africa ◽  
Socioeconomic Burden

Lassa virus (LASV), the causative agent of Lassa fever, is estimated to be responsible for up to 300,000 new infections and 5000 deaths each year across Western Africa. The most recent 2018 and 2019 Nigerian outbreaks featured alarmingly high fatality rates of up to 25.4%. In addition to the severity and high fatality of the disease, a significant population of survivors suffer from long-term sequelae, such as sensorineural hearing loss, resulting in a huge socioeconomic burden in endemic regions. There are no Food and Drug Administration (FDA)-approved vaccines, and therapeutics remain extremely limited for Lassa fever. Development of countermeasures depends on relevant animal models that can develop a disease strongly mimicking the pathogenic features of Lassa fever in humans. The objective of this review is to evaluate the currently available animal models for LASV infection with an emphasis on their pathogenic and histologic characteristics as well as recent advances in the development of a suitable rodent model. This information may facilitate the development of an improved animal model for understanding disease pathogenesis of Lassa fever and for vaccine or antiviral testing.

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