scholarly journals Effective Induction of Simian Immunodeficiency Virus-Specific Systemic and Mucosal Immune Responses in Primates by Vaccination with Proviral DNA Producing Intact but Noninfectious Virions

2000 ◽  
Vol 74 (22) ◽  
pp. 10514-10522 ◽  
Author(s):  
Shainn-Wei Wang ◽  
Pamela A. Kozlowski ◽  
Gretchen Schmelz ◽  
Kelledy Manson ◽  
Michael S. Wyand ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Dna Vaccine ◽  
Cytotoxic T Lymphocyte ◽  
Natural Infection ◽  
Immunoglobulin A ◽  
Rectal Mucosa ◽  
Immunodeficiency Virus ◽  
Mucosal Immune Responses ◽  
Lymphocyte Responses

ABSTRACT We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong virus-specific mucosal immune responses in primates. The levels of immunoglobulin A (IgA) detected in rectal secretions of macaques that received the DNA vaccine intradermally and at the rectal mucosa were the most striking of all measured immune responses and were higher than usually achieved through natural infection. However, cytotoxic T lymphocyte responses were generally low and sporadically present in different animals. Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected. Our results suggest that high levels of IgA alone are not sufficient to prevent the establishment of chronic infection, although mucosal IgA responses may have a role in reducing the infectivity of the initial viral inoculum.

scholarly journals Enhancement of Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus

2003 ◽  
Vol 77 (6) ◽  
pp. 3615-3623 ◽  
Author(s):  
Sang-Moo Kang ◽  
Richard W. Compans
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 4 ◽  
Cpg Odn ◽  
Virus Like Particles ◽  
Cpg Oligodeoxynucleotides ◽  
Immunodeficiency Virus ◽  
Helper Cell Type ◽  
Spleen And Lymph Nodes

ABSTRACT Cholera toxin (CT) is the most potent known mucosal adjuvant, but its toxicity precludes its use in humans. Here, in an attempt to develop safe and effective mucosal adjuvants, we compared immune responses to simian immunodeficiency virus (SIV) virus-like particles (VLPs) after intranasal coimmunization with RANTES, CpG oligodeoxynucleotides (ODN), or CT. Antibody analysis demonstrated that RANTES and CpG ODN had capacities for mucosal adjuvanticity, i.e., for enhancing serum and vaginal antibodies specific to SIV Env, similar to those for CT. RANTES and CpG ODN skewed serum antibodies predominantly to the immunoglobulin G2a isotype. Most importantly, RANTES and CpG ODN were more effective than CT in increasing neutralizing titers of both serum and vaginal antibodies. After intranasal coadministration with VLPs, RANTES or CpG ODN also induced increased levels of gamma interferon (IFN-γ)-producing lymphocyte and cytotoxic T-lymphocyte activities in both spleen and lymph nodes but did not increase the levels of interleukin-4-producing lymphocytes. The results suggest that RANTES and CpG ODN enhance immune responses in a T-helper-cell-type-1 (Th1)-oriented manner and that they can be used as effective mucosal adjuvants for enhancing both humoral and cellular immune responses in the context of VLPs, which are particulate antigens.

Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef

10.1038/15224 ◽  
1999 ◽  
Vol 5 (11) ◽  
pp. 1270-1276 ◽  
Author(s):  
David T. Evans ◽  
David H. O'Connor ◽  
Peicheng Jing ◽  
John L. Dzuris ◽  
John Sidney ◽  
...  
Keyword(s):  
Amino Acid ◽  
Simian Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Amino Acid Variation ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses

scholarly journals Protection against Simian Immunodeficiency Virus Vaginal Challenge by Using Sabin Poliovirus Vectors

2001 ◽  
Vol 75 (16) ◽  
pp. 7435-7452 ◽  
Author(s):  
Shane Crotty ◽  
Christopher J. Miller ◽  
Barbara L. Lohman ◽  
Martha R. Neagu ◽  
Lara Compton ◽  
...  
Keyword(s):  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Vaccination Strategy ◽  
Vaccine Vector ◽  
Mucosal Antibody ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Lymphocyte Responses ◽  
Pronounced Reduction ◽  
Human Vaccine

ABSTRACT Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag,pol, env, nef, andtat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV) were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to <103 copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population.

scholarly journals Cervicovaginal Lamina Propria Lymphocytes: Phenotypic Characterization and Their Importance in Cytotoxic T-Lymphocyte Responses to Simian Immunodeficiency Virus SIVmac251

2002 ◽  
Vol 76 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Liljana Stevceva ◽  
Brian Kelsall ◽  
Janos Nacsa ◽  
Marcin Moniuszko ◽  
Zdeněk Hel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Surface Expression ◽  
T Cell Response ◽  
Phenotypic Characterization ◽  
Immunodeficiency Virus

ABSTRACT Most human immunodeficiency virus (HIV) type 1 infections occur by the mucosal route. Thus, it is important to assess the immune responses to HIV in the vaginal, cervical, and rectal compartments. Here we quantitated the virus-specific CD8+ T-cell response and characterized the phenotype of lymphocytes in the genital tracts of naive macaques, macaques acutely or chronically infected with simian immunodeficiency virus SIVmac251, and macaques chronically infected with chimeric simian/human immunodeficiency virus SHIVKU2. Vaginal biopsy samples or samples obtained at the time of euthanasia were used in this analysis. The percentage of Gag-specific, tetramer-positive T cells was as high as 13 to 14% of the CD3+ CD8+ T-cell population in the vaginal and cervical laminae propriae of both SIVmac251 and SHIVKU2 chronically infected macaques. In most cases, the frequency of this response in the cervicovaginal compartment far exceeded the frequency in the blood or the draining iliac lymph node. Vaginal laminae propriae of naive macaques contained 55 to 65% CD3+ CD8+ cells and 28 to 34% CD3+ CD4+ cells, while the majority of intraepithelial cells were CD8+ T cells (75 to 85%). For the same cells, the surface expression of CD62L was low whereas that of αEβ7 was high. No difference in the expression of CD45RA on CD8+ T cells was observed in the chronic stage of SIVmac251 infection. Although no decrease in the percentage of CD4+ cells in the genital tract was observed within the first 12 days of infection, by 6 weeks from SIVmac251 infection and thereafter the percentage of CD4+ T cells was decreased in the laminae propriae of the vagina and cervix. Expression of CD45RA did not differ in naive and acutely SIVmac251 infected macaques. Information on the quality and quantity of local immune responses may help in the design of vaccine strategies aimed at containing viral replication at the site of viral encounter.

scholarly journals Mucosal Immunization of Cynomolgus Macaques with Two Serotypes of Live Poliovirus Vectors Expressing Simian Immunodeficiency Virus Antigens: Stimulation of Humoral, Mucosal, and Cellular Immunity

1999 ◽  
Vol 73 (11) ◽  
pp. 9485-9495 ◽  
Author(s):  
Shane Crotty ◽  
Barbara L. Lohman ◽  
Fabien X.-S. Lü ◽  
ShenBei Tang ◽  
Christopher J. Miller ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocytes ◽  
Cytotoxic T Lymphocyte ◽  
Immunoglobulin A ◽  
Live Virus ◽  
Mucosal Antibody ◽  
Immunodeficiency Virus ◽  
Cynomolgus Macaques

ABSTRACT Poliovirus live virus vectors are a candidate recombinant vaccine system. Previous studies using this system showed that a live poliovirus vector expressing a foreign antigen between the structural and nonstructural proteins generates both antibody and cytotoxic T-lymphocyte responses in mice. Here we describe a novel in vitro method of cloning recombinant polioviruses involving a hybrid-PCR approach. We report the construction of recombinant vectors of two different serotypes of poliovirus-expressing simian immunodeficiency virus (SIV) antigens and the intranasal and intravenous inoculations of four adult cynomolgus macaques with these poliovirus vectors expressing the SIV proteins p17 gag and gp41 env . All macaques generated a mucosal anti-SIV immunoglobulin A (IgA) response in rectal secretions. Two of the four macaques generated mucosal antibody responses detectable in vaginal lavages. Strong serum IgG responses lasting for at least 1 year were detected in two of the four monkeys. SIV-specific T-cell lymphoproliferative responses were detected in three of the four monkeys. SIV-specific cytotoxic T lymphocytes were detected in two of the four monkeys. This is the first report of poliovirus-elicited vaginal IgA or cytotoxic T lymphocytes in any naturally infectable primate, including humans. These findings support the concept that a live poliovirus vector is a potentially useful delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens.

scholarly journals Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus Conjugated with Cholera Toxin Subunit B

2003 ◽  
Vol 77 (18) ◽  
pp. 9823-9830 ◽  
Author(s):  
Sang-Moo Kang ◽  
Qizhi Yao ◽  
Lizheng Guo ◽  
Richard W. Compans
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Cytotoxic T Lymphocyte ◽  
Antigen Uptake ◽  
Virus Like Particles ◽  
Gag Proteins ◽  
Cellular Immune Responses ◽  
Mucosal Surfaces ◽  
Immunodeficiency Virus ◽  
Cellular Immune

ABSTRACT To enhance the efficiency of antigen uptake at mucosal surfaces, CTB was conjugated to simian immunodeficiency virus (SIV) virus-like particles (VLPs). We characterized the immune responses to the Env and Gag proteins after intranasal administration. Intranasal immunization with a mixture of VLPs and CTB as an adjuvant elicited higher levels of SIV gp160-specific immunoglobulin G (IgG) in sera and IgA in mucosae, including saliva, vaginal-wash samples, lung, and intestine, as well as a higher level of neutralization activities than immunization with VLPs alone. Conjugation of CTB to VLPs also enhanced the SIV VLP-specific antibodies in sera and in mucosae to similar levels. Interestingly, CTB-conjugated VLPs showed higher levels of cytokine (gamma interferon)-producing splenocytes and cytotoxic-T-lymphocyte activities of immune cells than VLPs plus CTB, as well as an increased level of both IgG1 and IgG2a serum antibodies, which indicates enhancement of both Th1- and Th2-type cellular immune responses. These results demonstrate that CTB can be an effective mucosal adjuvant in the context of VLPs to induce enhanced humoral, as well as cellular, immune responses.

Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

2005 ◽  
Vol 6 (3) ◽  
pp. 247-252 ◽  
Author(s):  
Dan H Barouch ◽  
Jennifer Powers ◽  
Diana M Truitt ◽  
Michael G Kishko ◽  
Janelle C Arthur ◽  
...  
Keyword(s):  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Immunodeficiency Virus
Sign in / Sign up

Export Citation Format

Share Document