scholarly journals A simultaneous oral and intramuscular prime/sublingual boost with a DNA/Modified Vaccinia Ankara viral vector-based vaccine induces simian immunodeficiency virus-specific systemic and mucosal immune responses in juvenile rhesus macaques

2018 ◽  
Vol 47 (5) ◽  
pp. 288-297 ◽  
Author(s):  
Alan D. Curtis ◽  
Kara Jensen ◽  
Koen K. A. Van Rompay ◽  
Rama R. Amara ◽  
Pamela A. Kozlowski ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Viral Vector ◽  
Rhesus Macaques ◽  
Immunodeficiency Virus ◽  
Mucosal Immune Responses

scholarly journals Induction of CD8+ Cells Able To Suppress CCR5-Tropic Simian Immunodeficiency Virus SIVmac239 Replication by Controlled Infection of CXCR4-Tropic Simian-Human Immunodeficiency Virus in Vaccinated Rhesus Macaques

2007 ◽  
Vol 81 (21) ◽  
pp. 11640-11649 ◽  
Author(s):  
Tetsuo Tsukamoto ◽  
Mitsuhiro Yuasa ◽  
Hiroyuki Yamamoto ◽  
Miki Kawada ◽  
Akiko Takeda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Viral Vector ◽  
Rhesus Macaques ◽  
Chronic Phase ◽  
Live Virus ◽  
Immunodeficiency Virus

ABSTRACT Recent recombinant viral vector-based AIDS vaccine trials inducing cellular immune responses have shown control of CXCR4-tropic simian-human immunodeficiency virus (SHIV) replication but difficulty in containment of pathogenic CCR5-tropic simian immunodeficiency virus (SIV) in rhesus macaques. In contrast, controlled infection of live attenuated SIV/SHIV can confer the ability to contain SIV superchallenge in macaques. The specific immune responses responsible for this control may be induced by live virus infection but not consistently by viral vector vaccination, although those responses have not been determined. Here, we have examined in vitro anti-SIV efficacy of CD8+ cells in rhesus macaques that showed prophylactic viral vector vaccine-based control of CXCR4-tropic SHIV89.6PD replication. Analysis of the effect of CD8+ cells obtained at several time points from these macaques on CCR5-tropic SIVmac239 replication in vitro revealed that CD8+ cells in the chronic phase after SHIV challenge suppressed SIV replication more efficiently than those before challenge. SIVmac239 superchallenge of two of these macaques at 3 or 4 years post-SHIV challenge was contained, and the following anti-CD8 antibody administration resulted in transient CD8+ T-cell depletion and appearance of plasma SIVmac239 viremia in both of them. Our results indicate that CD8+ cells acquired the ability to efficiently suppress SIV replication by controlled SHIV infection, suggesting the contribution of CD8+ cell responses induced by controlled live virus infection to containment of HIV/SIV superinfection.

scholarly journals Vaccine-induced immune responses against both Gag and Env improve control of simian immunodeficiency virus replication in rectally challenged rhesus macaques

2017 ◽  
Vol 13 (7) ◽  
pp. e1006529 ◽  
Author(s):  
Mauricio A. Martins ◽  
Young C. Shin ◽  
Lucas Gonzalez-Nieto ◽  
Aline Domingues ◽  
Martin J. Gutman ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Virus Replication ◽  
Rhesus Macaques ◽  
Immunodeficiency Virus

scholarly journals A Period of Transient Viremia and Occult Infection Precedes Persistent Viremia and Antiviral Immune Responses during Multiple Low-Dose Intravaginal Simian Immunodeficiency Virus Inoculations

2004 ◽  
Vol 78 (24) ◽  
pp. 14048-14052 ◽  
Author(s):  
Zhong-Min Ma ◽  
Kristina Abel ◽  
Tracy Rourke ◽  
Yichuan Wang ◽  
Christopher J. Miller
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Low Dose ◽  
Rhesus Macaques ◽  
Systemic Infection ◽  
Variable Number ◽  
Transmission Model ◽  
High Dose ◽  
Persistent Viremia ◽  
Immunodeficiency Virus

ABSTRACT In rhesus macaques, classic systemic infection, characterized by persistent viremia and seroconversion, occurred after multiple low-dose (103 50% tissue culture infective doses) intravaginal (IVAG) inoculations with simian immunodeficiency virus (SIV) strain SIVmac251. Monkeys developed classic SIV infections after a variable number of low-dose IVAG exposures to SIVmac251. Once established, the systemic infection was identical to SIV infection following high-dose IVAG SIV inoculation. However, occult systemic infection characterized by transient cell-associated or cell-free viremia consistently occurred early in the series of multiple vaginal SIV exposures. Further, antiviral cellular immune responses were present prior to the establishment of a classic systemic infection in the low-dose vaginal SIV transmission model.

scholarly journals Recombinant Herpesvirus Vectors: Durable Immune Responses and

2021 ◽  
Author(s):  
Isabelle M. Castro ◽  
Michael J. Ricciardi ◽  
Lucas Gonzalez-Nieto ◽  
Eva G. Rakasz ◽  
Jeffrey D. Lifson ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Antigen Expression ◽  
Challenge Virus ◽  
Immunodeficiency Virus ◽  
Herpesvirus Vector ◽  
Gamma Herpesvirus

A prophylactic vaccine that confers durable protection against human immunodeficiency virus (HIV) would provide a valuable tool to prevent new HIV/AIDS cases. As herpesviruses establish lifelong infections that remain largely subclinical, the use of persistent herpesvirus vectors to deliver HIV antigens may facilitate the induction of long-term anti-HIV immunity. We previously developed recombinant (r) forms of the gamma-herpesvirus rhesus monkey rhadinovirus (rRRV) expressing a replication-incompetent, near-full-length simian immunodeficiency virus (SIVnfl) genome. We recently showed that 8/16 rhesus macaques (RMs) vaccinated with a rDNA/rRRV-SIVnfl regimen were significantly protected against intrarectal (IR) challenge with SIVmac239. Here we investigated the longevity of this vaccine-mediated protection. Despite receiving no additional booster immunizations, the protected rDNA/rRRV-SIVnfl vaccinees maintained detectable cellular and humoral anti-SIV immune responses for more than 1.5 years after the rRRV boost. To assess if these responses were still protective, the rDNA/rRRV-SIVnfl vaccinees were subjected to a second round of marginal-dose IR SIVmac239 challenges, with eight SIV-naïve RMs serving as concurrent controls. After three SIV exposures, 8/8 control animals became infected, compared to 3/8 vaccinees. This difference in SIV acquisition was statistically significant (P = 0.0035). The three vaccinated monkeys that became infected exhibited significantly lower viral loads than those in unvaccinated controls. Collectively, these data illustrate the ability of rDNA/rRRV-SIVnfl vaccination to provide long-term immunity against stringent mucosal challenges with SIVmac239. Future work is needed to identify the critical components of this vaccine-mediated protection and the extent to which it can tolerate sequence mismatches in the challenge virus. IMPORTANCE We report on the long-term follow-up of a group of rhesus macaques (RMs) that received an AIDS vaccine regimen and were subsequently protected against rectal acquisition of simian immunodeficiency virus (SIV) infection. The vaccination regimen employed included a live recombinant herpesvirus vector that establishes persistent infection in RMs. Consistent with the recurrent SIV antigen expression afforded by this herpesvirus vector, vaccinees maintained detectable SIV-specific immune responses for more than 1.5 years after the last vaccination. Importantly, these vaccinated RMs were significantly protected against a second round of rectal SIV exposures performed one year after the first SIV challenge phase. These results are relevant for HIV vaccine development because they show the potential of herpesvirus-based vectors to maintain functional antiretroviral immunity without the need for repeated boosting.

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 Vaccine protection from CD4+ T-cell loss caused by simian immunodeficiency virus (SIV) mac251 is afforded by sequential immunization with three unrelated vaccine vectors encoding multiple SIV antigens

2004 ◽  
Vol 85 (10) ◽  
pp. 2915-2924 ◽  
Author(s):  
Gerrit Koopman ◽  
Daniella Mortier ◽  
Sam Hofman ◽  
Henk Niphuis ◽  
Zahra Fagrouch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cell Function ◽  
Semliki Forest Virus ◽  
Rhesus Macaques ◽  
Cell Loss ◽  
Inverse Association ◽  
Immunodeficiency Virus

Candidate human immunodeficiency virus (HIV) vaccine strategies that induce strong cellular immune responses protect rhesus macaques that are infected with recombinant simian/human immunodeficiency virus SHIV89.6p from acute CD4+ T-cell loss and delay progression to AIDS. However, similar strategies have not proven as efficacious in the simian immunodeficiency virus (SIV)mac model of AIDS, an infection that causes a slow, steady loss of CD4+ T-cell function and numbers in rhesus macaques similar to that caused by HIV-1, the principal cause of AIDS in humans. Efforts to increase vaccine efficacy by repeated boosting with the same vector are quickly limited by rising anti-vector immune responses. Here, the sequential use of three different vectors (DNA, Semliki Forest virus and modified vaccinia virus Ankara) encoding the same SIVmac structural and regulatory antigens was investigated and demonstrated to prevent or slow the loss of CD4+ T-cells after mucosal challenge with the highly pathogenic SIVmac251 strain. Of particular interest was an inverse association between the extent of T-helper 2 cytokine responses and steady-state virus load. Although limited in the number of animals, this study provides important proof of the efficacy of the triple-vector vaccine strategy against chronic, progressive CD4+ T-cell loss in the rigorous SIVmac/rhesus macaque model of AIDS.

scholarly journals Recombinant Mycobacterium bovis Bacillus Calmette-Guérin Vectors Prime for Strong Cellular Responses to Simian Immunodeficiency Virus Gag in Rhesus Macaques

2014 ◽  
Vol 21 (10) ◽  
pp. 1385-1395 ◽  
Author(s):  
Jaimie D. Sixsmith ◽  
Michael W. Panas ◽  
Sunhee Lee ◽  
Geoffrey O. Gillard ◽  
KeriAnn White ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Mycobacterium Bovis ◽  
Rhesus Macaques ◽  
Vaccine Vector ◽  
Effective Vaccine ◽  
Bacillus Calmette Guerin ◽  
Immunodeficiency Virus ◽  
Specific Priming

ABSTRACTLive attenuated nonpathogenicMycobacterium bovisbacillus Calmette-Guérin (BCG) mediates long-lasting immune responses, has been safely administered as a tuberculosis vaccine to billions of humans, and is affordable to produce as a vaccine vector. These characteristics make it very attractive as a human immunodeficiency virus (HIV) vaccine vector candidate. Here, we assessed the immunogenicity of recombinant BCG (rBCG) constructs with different simian immunodeficiency virus (SIV)gagexpression cassettes as priming agents followed by a recombinant replication-incompetent New York vaccinia virus (NYVAC) boost in rhesus macaques. Unmutated rBCG constructs were used in comparison to mutants with gene deletions identified in anin vitroscreen for augmented immunogenicity. We demonstrated that BCG-SIVgagis able to elicit robust transgene-specific priming responses, resulting in strong SIV epitope-specific cellular immune responses. While enhanced immunogenicity was sustained at moderate levels for >1 year following the heterologous boost vaccination, we were unable to demonstrate a protective effect after repeated rectal mucosal challenges with pathogenic SIVmac251. Our findings highlight the potential for rBCG vaccines to stimulate effective cross-priming and enhanced major histocompatibility complex class I presentation, suggesting that combining this approach with other immunogens may contribute to the development of effective vaccine regimens against HIV.

scholarly journals Factors Associated with Slow Disease Progression in Macaques Immunized with an Adenovirus-Simian Immunodeficiency Virus (SIV) Envelope Priming-gp120 Boosting Regimen and Challenged Vaginally with SIVmac251

1999 ◽  
Vol 73 (9) ◽  
pp. 7430-7440 ◽  
Author(s):  
Suzan L. Buge ◽  
Lalita Murty ◽  
Kamalpreet Arora ◽  
V. S. Kalyanaraman ◽  
Phillip D. Markham ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Progression ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Viral Envelope ◽  
Virus Envelope ◽  
Partial Protection ◽  
Vaccine Regimen ◽  
Cd4 Counts ◽  
Immunodeficiency Virus

ABSTRACT Rhesus macaques were immunized with a combination vaccine regimen consisting of adenovirus type 5 host range mutant-simian immunodeficiency virus envelope (Ad5hr-SIVenv) recombinant priming and boosting with native SIV gp120. Upon intravaginal challenge with SIVmac251, both persistently and transiently viremic animals were observed (S. L. Buge, E. Richardson, S. Alipanah, P. Markham, S. Cheng, N. Kalyan, C. J. Miller, M. Lubeck, S. Udem, J. Eldridge, and M. Robert-Guroff, J. Virol. 71:8531–8541, 1997). Long-term follow-up of the persistently viremic immunized macaques, which displayed significantly reduced viral burdens during the first 18 weeks postchallenge compared to controls, has now shown that one of four became a slow progressor, clearing virus from plasma and remaining asymptomatic with stable CD4 counts for 134 weeks postchallenge. Reboosting of the transiently viremic macaques did not reactivate latent virus. Rechallenge with two sequential SIVmac251 intravaginal exposures again resulted in partial protection of one of two immunized macaques, manifested by viral clearance and stable CD4 counts. No single immune parameter was associated with partial protection. Development of a strong antibody response capable of neutralizing a primary SIVmac251 isolate together with SIV-specific cytotoxic T lymphocytes were implicated, while CD8+ T-cell antiviral activity and mucosal immune responses were not associated with delayed disease progression. Our data show that even a third immunization with the same Ad5hr-SIVenv recombinant can elicit significant immune responses to the inserted gene product, suggesting that preexisting Ad antibodies may not preclude effective immunization. Further, the partial protection against a virulent, pathogenic SIV challenge observed in two of six macaques immunized with a vaccine regimen based solely on the viral envelope indicates that this vectored-vaccine approach has promise and that multicomponent vaccines based in the same system merit further investigation.

scholarly journals Effect of CD8+ Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques

2005 ◽  
Vol 79 (13) ◽  
pp. 8131-8141 ◽  
Author(s):  
Jörn E. Schmitz ◽  
R. Paul Johnson ◽  
Harold M. McClure ◽  
Kelledy H. Manson ◽  
Michael S. Wyand ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Intravenous Route ◽  
Partial Control ◽  
Challenge Virus ◽  
Lymphocyte Depletion ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune

ABSTRACT Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8+ lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239Δ3 of CD8+ lymphocytes and then challenged them with SIVmac251 by the intravenous route. While vaccination did not prevent infection with the pathogenic challenge virus, the postchallenge levels of virus in the plasmas of vaccinated control animals were significantly lower than those for unvaccinated animals. The depletion of CD8+ lymphocytes at the time of challenge resulted in virus levels in the plasma that were intermediate between those of the vaccinated and unvaccinated controls, suggesting that CD8+ cell-mediated immune responses contributed to protection. Interestingly, at the time of challenge, animals expressing the Mamu-A*01 major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8+ T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01 − animals. Consistent with these findings, the depletion of CD8+ lymphocytes abrogated vaccine-induced protection, as judged by the peak postchallenge viremia, to a greater extent in Mamu-A*01 + than in Mamu-A*01 − animals. The partial control of postchallenge viremia after CD8+ lymphocyte depletion suggests that both humoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined.

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