scholarly journals SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Science ◽  
2020 ◽  
Vol 369 (6505) ◽  
pp. 812-817 ◽  
Author(s):  
Abishek Chandrashekar ◽  
Jinyan Liu ◽  
Amanda J. Martinot ◽  
Katherine McMahan ◽  
Noe B. Mercado ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Viral Loads ◽  
Macaque Model ◽  
Cellular Immune Responses ◽  
Immunologic Control ◽  
Cellular Immune ◽  
Public Health Strategies

An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.

scholarly journals Improved Protection of Rhesus Macaques against Intrarectal Simian Immunodeficiency Virus SIVmac251 Challenge by a Replication-Competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag Recombinant Priming/gp120 Boosting Regimen

2003 ◽  
Vol 77 (15) ◽  
pp. 8354-8365 ◽  
Author(s):  
Jun Zhao ◽  
Joel Pinczewski ◽  
Victor R. Gómez-Román ◽  
David Venzon ◽  
V. S. Kalyanaraman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Acute Infection ◽  
Neutralizing Antibody ◽  
Antibody Activity ◽  
Viral Loads ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune

ABSTRACT In this study we investigated the ability of a replication-competent Ad5hr-SIVenv/rev and Ad5hr-SIVgag recombinant priming/gp120 boosting regimen to induce protective immunity in rhesus macaques against pathogenic simian immunodeficiency virusmac251. Immunization of macaques by two sequential administrations of the same recombinants by the same route resulted in boosting and persistence of SIV-specific cellular immune responses for 42 weeks past the initial immunization. Anti-SIV gp120 immunoglobulin G (IgG) and IgA antibodies were induced in secretory fluids, and all macaques exhibited serum neutralizing antibody activity. After intrarectal SIVmac251 challenge, all of the macaques became infected. However, relative protection, as assessed by statistically significant lower SIV viral loads in plasma at both acute infection and set point, was observed in 8 out of 12 immunized non-Mamu-A∗01 animals. Elevated mean cellular immune responses to Gag and Env, neutralizing antibody activity, and IgG and IgA binding antibody levels were observed in the eight protected macaques. Statistically significant correlations with protective outcome were observed for cellular immune responses to SIV Env and Gag and for SIV gp120-specific IgG antibodies in nasal and vaginal fluids. Two macaques that exhibited the greatest and most persistent viremia control also exhibited strong CD8+ T-cell antiviral activity. The results suggest that a spectrum of immune responses may be necessary for adequate control of viral replication and disease progression and highlight a potential role for nonneutralizing antibodies at mucosal sites.

scholarly journals Recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to SIV and reduce viral loads in immunized rhesus macaques

Vaccine ◽  
2010 ◽  
Vol 28 (39) ◽  
pp. 6483-6490 ◽  
Author(s):  
V. Traina-Dorge ◽  
B. Pahar ◽  
P. Marx ◽  
P. Kissinger ◽  
D. Montefiori ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Viral Loads ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Protective Efficacy of an Inactive Vaccine Based on the LY02 Isolate against AcuteHaemophilus parasuisInfection in Piglets

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Hua Li ◽  
Guo-Zhen Zhao ◽  
Long-Xin Qiu ◽  
Ai-Ling Dai ◽  
Wang-Wei Wu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Haemophilus Parasuis ◽  
Fujian Province ◽  
Cellular Immune Responses ◽  
Glässer’S Disease ◽  
Potential Vaccine ◽  
Cellular Immune ◽  
Glasser's Disease

Haemophilus parasuiscan cause Glässer’s disease characterized by fibrinous polyserositis, polyarthritis, and meningitis. The current prevention of Glässer’s disease is mainly based on the inactive vaccines; however, the protective efficacy usually fails in heterogeneous or homologous challenges. Here, the predominant lineage ofH. parasuis(LY02 strain) in Fujian province, China, characterized as serovar 5, was used to evaluate the protective immunity against acuteH. parasuisinfection in piglets after inactivation. Following challenging withH. parasuis,only mild lesions in the pigs immunized with the killed vaccine were observed, whereas the typical symptoms of Glässer’s disease presented in the nonimmunized piglets. A strong IgG immune response was induced by the inactive vaccine. CD4+and CD8+T lymphocyte levels were increased, indicating the potent cellular immune responses were elicited. The significantly high levels of IL-2, IL-4, TGF-β, and IFN-γin sera from pigs immunized with this killed vaccine suggested that the mixed Th1 and Th2 immune responses were induced, associated with the high protection againstH. parasuisinfection compared to the nonimmunized animals. This study indicated that the inactivated LY02 strain ofH. parasuiscould serve as a potential vaccine candidate to prevent the prevalence ofH. parasuisin Fujian province, China.

scholarly journals Strong HCV NS3- and NS4A-specific cellular immune responses induced in mice and Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine

Vaccine ◽  
2008 ◽  
Vol 26 (49) ◽  
pp. 6225-6231 ◽  
Author(s):  
Krystle A. Lang ◽  
Jian Yan ◽  
Ruxandra Draghia-Akli ◽  
Amir Khan ◽  
David B. Weiner
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Rhesus Macaques ◽  
Hcv Genotype ◽  
Cellular Immune Responses ◽  
Genotype 1A ◽  
Cellular Immune

scholarly journals Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses

2002 ◽  
Vol 76 (6) ◽  
pp. 2817-2826 ◽  
Author(s):  
Georg M. Lauer ◽  
Tam N. Nguyen ◽  
Cheryl L. Day ◽  
Gregory K. Robbins ◽  
Theresa Flynn ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
T Lymphocyte ◽  
Viral Loads ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8+- and CD4+-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8+-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8+-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative response against any HCV protein was found in these coinfected persons. These data demonstrate a major discordance in immune responses to two persistent RNA viruses. In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons.

scholarly journals Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine

2014 ◽  
Vol 10 (8) ◽  
pp. 2357-2365 ◽  
Author(s):  
Brian Latimer ◽  
Roberta Toporovski ◽  
Jian Yan ◽  
Panyupa Pankhong ◽  
Matthew P Morrow ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Rhesus Macaques ◽  
Hcv Genotype ◽  
Cellular Immune Responses ◽  
Genotype 1A ◽  
Cellular Immune

scholarly journals Th-1-Type Cytotoxic CD8+ T-Lymphocyte Responses to Simian Immunodeficiency Virus (SIV) Are a Consistent Feature of Natural SIV Infection in Sooty Mangabeys

2006 ◽  
Vol 80 (6) ◽  
pp. 2771-2783 ◽  
Author(s):  
Zichun Wang ◽  
Benjamin Metcalf ◽  
Ruy M. Ribeiro ◽  
Harold McClure ◽  
Amitinder Kaur
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Rhesus Macaques ◽  
Elispot Response ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Sooty Mangabeys ◽  
Siv Infection ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Sooty mangabeys are a natural host of simian immunodeficiency virus (SIV) that remain asymptomatic and do not exhibit increased immune activation or increased T-lymphocyte turnover despite sustained high levels of SIV viremia. In this study we asked whether an altered immune response to SIV contributes to the lack of immunopathology in sooty mangabeys as opposed to species with pathogenic lentivirus infection. SIV-specific cellular immune responses were investigated in a cohort of 25 sooty mangabeys with natural SIV infection. Gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses targeting a median of four SIV proteins were detected in all 25 mangabeys and were comparable in magnitude to those of 13 rhesus macaques infected with SIVmac251 for more than 6 months. As with rhesus macaques, Th2 ELISPOT responses to SIV were absent or >10-fold lower than the IFN-γ ELISPOT response to the same SIV protein. The SIV-specific ELISPOT response was predominantly mediated by CD8+ T lymphocytes; the frequency of circulating SIV-specific CD8+ T lymphocytes ranged between 0.11% and 3.26% in 13 mangabeys. Functionally, the SIV-specific CD8+ T lymphocytes were cytotoxic; secreted IFN-γ, tumor necrosis factor alpha, and macrophage inflammatory protein 1β; and had an activated effector phenotype. Although there was a trend toward higher frequencies of SIV-specific CD8+ T lymphocytes in mangabeys with lower viral loads, a significant inverse correlation between SIV viremia and SIV-specific cellular immunity was not detected. The consistent detection of Th1-type SIV-specific cellular immune responses in naturally infected sooty mangabeys suggests that immune attenuation is neither a feature of nor a requirement for maintenance of nonpathogenic SIV infection in its natural host.

scholarly journals Aerosol Vaccination with AERAS-402 Elicits Robust Cellular Immune Responses in the Lungs of Rhesus Macaques but Fails To Protect against High-DoseMycobacterium tuberculosisChallenge

2014 ◽  
Vol 193 (4) ◽  
pp. 1799-1811 ◽  
Author(s):  
Patricia A. Darrah ◽  
Diane L. Bolton ◽  
Andrew A. Lackner ◽  
Deepak Kaushal ◽  
Pyone Pyone Aye ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rhesus Macaques ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

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