scholarly journals Of mice, macaques and men: scaling of virus dynamics and immune responses

2015 ◽  
Author(s):  
Christian L Althaus
Keyword(s):  
Immune Responses ◽  
Allometric Scaling ◽  
Rhesus Macaques ◽  
Lymphocytic Choriomeningitis ◽  
The Body ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Infection Dynamics ◽  
Immunodeficiency Virus ◽  
Cellular Immune

In this Opinion piece, I argue that the dynamics of viruses and the cellular immune response depend on the body size of the host. I use allometric scaling theory to interpret observed quantitative differences in the infection dynamics of lymphocytic choriomeningitis virus (LCMV) in mice (Mus musculus), simian immunodeficiency virus (SIV) in rhesus macaques (Macaca mulatta) and human immunodeficiency virus (HIV) in humans. There are indications that viral replication and the proliferation of CD8+ T cell responses are slower in larger animals. Whether this influences the ability of the cellular immune responses to eradicate viruses during the acute phase of an infection remains unclear, however.

scholarly journals Of mice, macaques and men: scaling of virus dynamics and immune responses

2015 ◽  
Author(s):  
Christian L Althaus
Keyword(s):  
Immune Responses ◽  
Allometric Scaling ◽  
Rhesus Macaques ◽  
Lymphocytic Choriomeningitis ◽  
The Body ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Infection Dynamics ◽  
Immunodeficiency Virus ◽  
Cellular Immune

In this Opinion piece, I argue that the dynamics of viruses and the cellular immune response depend on the body size of the host. I use allometric scaling theory to interpret observed quantitative differences in the infection dynamics of lymphocytic choriomeningitis virus (LCMV) in mice (Mus musculus), simian immunodeficiency virus (SIV) in rhesus macaques (Macaca mulatta) and human immunodeficiency virus (HIV) in humans. There are indications that viral replication and the proliferation of CD8+ T cell responses are slower in larger animals. Whether this influences the ability of the cellular immune responses to eradicate viruses during the acute phase of an infection remains unclear, however.

scholarly journals Of mice, macaques and men: scaling of virus dynamics and immune responses

2015 ◽  
Author(s):  
Christian L Althaus
Keyword(s):  
Body Size ◽  
Viral Infections ◽  
Rhesus Macaques ◽  
Lymphocytic Choriomeningitis ◽  
The Body ◽  
Cell Responses ◽  
Infection Dynamics ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Kinetics Of

In this Opinion piece, I argue that the dynamics of viruses and the cellular immune response depend on the body size of the host. I use allometric scaling theory to interpret observed quantitative differences in the infection dynamics of lymphocytic choriomeningitis virus (LCMV) in mice (Mus musculus), simian immunodeficiency virus (SIV) in rhesus macaques (Macaca mulatta) and human immunodeficiency virus (HIV) in humans. However, additional data on the kinetics of virus replication and the dynamics of T cell responses in different host species will be required to shed more light on the question whether the nature of viral infections is affected by the body size of their hosts.

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 Magnitude and Quality of Vaccine-Elicited T-Cell Responses in the Control of Immunodeficiency Virus Replication in Rhesus Monkeys

2008 ◽  
Vol 82 (17) ◽  
pp. 8812-8819 ◽  
Author(s):  
Yue Sun ◽  
Sampa Santra ◽  
Jörn E. Schmitz ◽  
Mario Roederer ◽  
Norman L. Letvin
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Rhesus Monkeys ◽  
T Cell Responses ◽  
Viral Control ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Functional Profiles

ABSTRACT While a diversity of immunogens that elicit qualitatively different cellular immune responses are being assessed in clinical human immunodeficiency virus vaccine trials, the consequences of those varied responses for viral control remain poorly understood. In the present study, we evaluated the induction of virus-specific T-cell responses in rhesus monkeys using a series of diverse vaccine vectors. We assessed both the magnitude and the functional profile of the virus-specific CD8+ T cells by measuring gamma interferon, interleukin-2, and tumor necrosis factor alpha production. We found that the different vectors generated virus-specific T-cell responses of different magnitudes and with different functional profiles. Heterologous prime-boost vaccine regimens induced particularly high-frequency virus-specific T-cell responses with polyfunctional repertoires. Yet, immediately after a pathogenic simian-human immunodeficiency virus (SHIV) challenge, no significant differences were observed between these cohorts of vaccinated monkeys in the magnitudes or the functional profiles of their virus-specific CD8+ T cells. This finding suggests that the high viral load shapes the functional repertoire of the cellular immune response during primary infection. Nevertheless, in all vaccination regimens, higher frequency and more polyfunctional vaccine-elicited virus-specific CD8+ T-cell responses were associated with better viral control after SHIV challenge. These observations highlight the contributions of both the quality and the magnitude of vaccine-elicited cellular immune responses in the control of immunodeficiency virus replication.

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 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.

scholarly journals Induction of Neutralizing Antibodies and Gag-Specific Cellular Immune Responses to an R5 Primary Isolate of Human Immunodeficiency Virus Type 1 in Rhesus Macaques

2001 ◽  
Vol 75 (13) ◽  
pp. 5879-5890 ◽  
Author(s):  
David C. Montefiori ◽  
Jeffrey T. Safrit ◽  
Shari L. Lydy ◽  
Ashley P. Barry ◽  
Miroslawa Bilska ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Hiv 1

ABSTRACT The ability to generate antibodies that cross-neutralize diverse primary isolates is an important goal for human immunodeficiency virus type 1 (HIV-1) vaccine development. Most of the candidate HIV-1 vaccines tested in humans and nonhuman primates have failed in this regard. Past efforts have focused almost entirely on the envelope glycoproteins of a small number of T-cell line-adapted strains of the virus as immunogens. Here we assessed the immunogenicity of noninfectious virus-like particles (VLP) consisting of Gag, Pro (protease), and Env from R5 primary isolate HIV-1Bx08. Immunogens were delivered to rhesus macaques in the form of either purified VLP, recombinant DNA and canarypox (ALVAC) vectors engineered to express VLP, or a combination of these products. Seroconversion to Gag and Pro was detected in all of the immunized animals. Antibodies that could neutralize HIV-1Bx08 were detected in animals that received (i) coinoculations with DNABx08 and VLPBx08, (ii) DNABx08 followed by ALVACBx08 boosting, and (iii) VLPBx08 alone. The neutralizing antibodies were highly strain specific despite the fact that they did not appear to be directed to linear epitopes in the V3 loop. Virus-specific cellular immune responses also were generated, as judged by the presence of Gag-specific gamma interferon (IFN-γ)-producing cells. These cellular immune responses required the inclusion of DNABx08 in the immunization modality, since few or no IFN-γ-producing cells were detected in animals that received either VLPBx08 or ALVACBx08 alone. The results demonstrate the feasibility of generating neutralizing antibodies and cellular immune responses that target an R5 primary HIV-1 isolate by vaccination in primates.

scholarly journals Dynamics of T-Cell Responses and Memory T Cells during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques

2007 ◽  
Vol 81 (24) ◽  
pp. 13456-13468 ◽  
Author(s):  
Ingrid Karlsson ◽  
Benoît Malleret ◽  
Patricia Brochard ◽  
Benoît Delache ◽  
Julien Calvo ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Peripheral Blood ◽  
Primary Infection ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques ◽  
Cellular Immune

ABSTRACT Cellular immune responses make an important contribution to both the control of human immunodeficiency virus (HIV) replication and disease progression. We used a pathogenic model of SIVmac251 infection of cynomolgus macaques to longitudinally evaluate cellular immune responses in association with various rates of disease progression. We found an inverse relationship between plasma viral load and the simian immunodeficiency virus (SIV)-specific T cells responses in peripheral blood and lymph nodes. SIV-specific T-cell responses in peripheral blood were transient during primary infection, with the highest responses detected around 3 months after infection. There was also a transient increase of central memory CD8+ T cells in peripheral blood during primary infection, and effector memory T-cell counts in peripheral lymph nodes were increased. This study emphasizes the importance of the early virus-specific immune responses in the outcome of HIV/SIV disease and provides details about the changes of virus-specific immune responses over time.

scholarly journals Adoptive Transfer of Engineered Rhesus Simian Immunodeficiency Virus-Specific CD8 + T Cells Reduces the Number of Transmitted/Founder Viruses Established in Rhesus Macaques

2016 ◽  
Vol 90 (21) ◽  
pp. 9942-9952 ◽  
Author(s):  
Victor I. Ayala ◽  
Matthew T. Trivett ◽  
Eugene V. Barsov ◽  
Sumiti Jain ◽  
Michael Piatak ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Rhesus Macaques ◽  
High Dose ◽  
Cell Responses ◽  
Large Numbers ◽  
Immunodeficiency Virus ◽  
Virus Exposure ◽  
Cellular Immune

ABSTRACT AIDS virus infections are rarely controlled by cell-mediated immunity, in part due to viral immune evasion and immunodeficiency resulting from CD4 + T-cell infection. One likely aspect of this failure is that antiviral cellular immune responses are either absent or present at low levels during the initial establishment of infection. To test whether an extensive, timely, and effective response could reduce the establishment of infection from a high-dose inoculum, we adoptively transferred large numbers of T cells that were molecularly engineered with anti-simian immunodeficiency virus (anti-SIV) activity into rhesus macaques 3 days following an intrarectal SIV inoculation. To measure in vivo antiviral activity, we assessed the number of viruses transmitted using SIVmac239X, a molecularly tagged viral stock containing 10 genotypic variants, at a dose calculated to transmit 12 founder viruses. Single-genome sequencing of plasma virus revealed that the two animals receiving T cells expressing SIV-specific T-cell receptors (TCRs) had significantly fewer viral genotypes than the two control animals receiving non-SIV-specific T cells (means of 4.0 versus 7.5 transmitted viral genotypes; P = 0.044). Accounting for the likelihood of transmission of multiple viruses of a particular genotype, the calculated means of the total number of founder viruses transmitted were 4.5 and 14.5 in the experimental and control groups, respectively ( P = 0.021). Thus, a large antiviral T-cell response timed with virus exposure can limit viral transmission. The presence of strong, preexisting T-cell responses, including those induced by vaccines, might help prevent the establishment of infection at the lower-exposure doses in humans that typically transmit only a single virus. IMPORTANCE The establishment of AIDS virus infection in an individual is essentially a race between the spreading virus and host immune defenses. Cell-mediated immune responses induced by infection or vaccination are important contributors in limiting viral replication. However, in human immunodeficiency virus (HIV)/SIV infection, the virus usually wins the race, irreversibly crippling the immune system before an effective cellular immune response is developed and active. We found that providing an accelerated response by adoptively transferring large numbers of antiviral T cells shortly after a high-dose mucosal inoculation, while not preventing infection altogether, limited the number of individual viruses transmitted. Thus, the presence of strong, preexisting T-cell responses, including those induced by vaccines, might prevent infection in humans, where the virus exposure is considerably lower.

Cellular immune responses in rhesus macaques infected rectally with low dose simian immunodeficiency virus

1994 ◽  
Vol 23 (2-3) ◽  
pp. 125-130 ◽  
Author(s):  
Maria S. Salvato ◽  
Peter Emau ◽  
Miroslav Malkovsky ◽  
Kevin T. Schultz ◽  
Eric Johnson ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Low Dose ◽  
Rhesus Macaques ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune
Sign in / Sign up

Export Citation Format

Share Document