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Article ; Online: Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis.

Cafaro, Aurelio / Schietroma, Ivan / Sernicola, Leonardo / Belli, Roberto / Campagna, Massimo / Mancini, Flavia / Farcomeni, Stefania / Pavone-Cossut, Maria Rosaria / Borsetti, Alessandra / Monini, Paolo / Ensoli, Barbara

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: Each time the virus starts a new round of expression/replication, even under effective antiretroviral therapy (ART), the transactivator of viral transcription Tat is one of the first HIV-1 protein to be produced, as it is strictly required for HIV ... ...

Abstract	Each time the virus starts a new round of expression/replication, even under effective antiretroviral therapy (ART), the transactivator of viral transcription Tat is one of the first HIV-1 protein to be produced, as it is strictly required for HIV replication and spreading. At this stage, most of the Tat protein exits infected cells, accumulates in the extracellular matrix and exerts profound effects on both the virus and neighbor cells, mostly of the innate and adaptive immune systems. Through these effects, extracellular Tat contributes to the acquisition of infection, spreading and progression to AIDS in untreated patients, or to non-AIDS co-morbidities in ART-treated individuals, who experience inflammation and immune activation despite virus suppression. Here, we review the role of extracellular Tat in both the virus life cycle and on cells of the innate and adaptive immune system, and we provide epidemiological and experimental evidence of the importance of targeting Tat to block residual HIV expression and replication. Finally, we briefly review vaccine studies showing that a therapeutic Tat vaccine intensifies ART, while its inclusion in a preventative vaccine may blunt escape from neutralizing antibodies and block early events in HIV acquisition.
MeSH term(s)	Humans ; HIV Infections ; HIV-1/metabolism ; tat Gene Products, Human Immunodeficiency Virus/metabolism ; Antibodies, Neutralizing ; Vaccines/therapeutic use
Chemical Substances	tat Gene Products, Human Immunodeficiency Virus ; Antibodies, Neutralizing ; Vaccines
Language	English
Publishing date	2024-01-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031704
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Article ; Online: Linear trichoepithelioma on the neck of a 15-year-old girl.

Laska, Amanda J / Belli, Roberto A / Kobayashi, Todd T

Dermatology online journal

2016 Volume 22, Issue 11

Abstract: Trichoepitheliomas are trichogenic tumors that can have various clinical morphologies. These tumors are benign and differentiate toward the outer root sheath of the hair follicle. Solitary trichoepitheliomas arise sporadically, in contrast to multiple ... ...

Abstract	Trichoepitheliomas are trichogenic tumors that can have various clinical morphologies. These tumors are benign and differentiate toward the outer root sheath of the hair follicle. Solitary trichoepitheliomas arise sporadically, in contrast to multiple trichoepitheliomas, which are usually inherited as an autosomal dominant trait or as part of various genetic syndromes. We report a case of an adolescent female with a linear array of trichoepitheliomas on her left neck.
MeSH term(s)	Adolescent ; Female ; Hair Diseases/diagnosis ; Hair Diseases/pathology ; Humans ; Neck ; Neoplasms, Multiple Primary/diagnosis ; Neoplasms, Multiple Primary/pathology ; Skin Neoplasms/diagnosis ; Skin Neoplasms/pathology
Language	English
Publishing date	2016-11-15
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2026239-5
ISSN	1087-2108 ; 1087-2108
ISSN (online)	1087-2108
ISSN	1087-2108
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Article ; Online: Eruptive xanthomas as a cutaneous manifestation of hypertriglyceridemia: a case report.

Digby, Michael / Belli, Roberto / McGraw, Timothy / Lee, Abigail

The Journal of clinical and aesthetic dermatology

2011 Volume 4, Issue 1, Page(s) 44–46

Abstract: A 28-year-old veteran presented to the Wilford Hall dermatology clinic in San Antonio, Texas, with a six-month history of a rash that his primary care physician diagnosed as molluscum contagiosum. The rash consisted of clusters of 3 to 6mm yellowish ... ...

Abstract	A 28-year-old veteran presented to the Wilford Hall dermatology clinic in San Antonio, Texas, with a six-month history of a rash that his primary care physician diagnosed as molluscum contagiosum. The rash consisted of clusters of 3 to 6mm yellowish papules with erythematous borders that concentrated on the extensor surfaces of his extremities, lower back, and buttocks. A biopsy determined that the patient had a case of eruptive xanthoma. Subsequent laboratory testing revealed that the patient had a type IV familial hyperlipidemia with a triglyceride count of 1718mg/dL.
Language	English
Publishing date	2011-01-21
Publishing country	United States
Document type	Case Reports
ISSN	2689-9175
ISSN (online)	2689-9175
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Article ; Online: Semirecumbent position to prevent ventilator-associated pneumonia is not evidence based.

Silvestri, Luciano / Gregori, Dario / van Saene, Hendrick K F / Belli, Roberto / Blazic, Miranda

Journal of critical care

2010 Volume 25, Issue 1, Page(s) 152–3; author reply 153–4

MeSH term(s)	Evidence-Based Medicine ; Humans ; Meta-Analysis as Topic ; Pneumonia, Ventilator-Associated/prevention & control ; Research Design ; Supine Position
Language	English
Publishing date	2010-03
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	632818-0
ISSN	1557-8615 ; 0883-9441
ISSN (online)	1557-8615
ISSN	0883-9441
DOI	10.1016/j.jcrc.2009.08.002
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Article ; Online: High HIV-1 diversity in immigrants resident in Italy (2008-2017).

Maggiorella, Maria Teresa / Sanarico, Nunzia / Brindicci, Gaetano / Monno, Laura / Santoro, Carmen Rita / Coppola, Nicola / Cuomo, Nunzia / Azzurri, Annalisa / Cesario, Francesco / Luciani, Filippo / El-Hamad, Issa / D'Ettorre, Gabriella / Turriziani, Ombretta / Mazzuti, Laura / Poggi, Alessandra / Vichi, Francesca / Mariabelli, Elisa / Surace, Lorenzo / Berardelli, Giuseppina /

Picconi, Orietta / Cenci, Alessandra / Sernicola, Leonardo / Rovetto, Claudia / Fulgenzi, Domenico / Belli, Roberto / Salvi, Emanuela / Zeo, Patrizia Di / Borsetti, Alessandra / Ridolfi, Barbara / Losappio, Ruggero / Zoboli, Fabio / Schietroma, Ivan / Cella, Eleonora / Angeletti, Silvia / Ciccozzi, Massimo / D'Amato, Stefania / Ensoli, Barbara / Buttò, Stefano

Scientific reports

2020 Volume 10, Issue 1, Page(s) 3226

Abstract: The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective study was performed in 557 HIV-infected immigrants ... ...

Abstract	The proportion of new diagnoses of HIV infection in immigrants residing in Italy raised from 11% in 1992 to 29.7% in 2018. To investigate the HIV clades circulating in this community a retrospective study was performed in 557 HIV-infected immigrants living in 12 Italian cities. Immigrants originated from East-Europe and Central-Asia (11.7%), North Africa and Middle East (7.3%), South and South-East Asia (7.2%), Latin America and the Caribbean (14.4%), and sub-Saharan Africa (59.4%). More than 87% of immigrants were on antiretroviral therapy (ART), although 26.6% of them were viremic. A 22.0% of immigrants had hepatitis (HBV and/or HCV) and/or tuberculosis. HIV phylogenetic analysis on sequences from 192 immigrants showed the presence of clades B (23.4%), G (16.1%), C (10.4%), A1 (9.4%), F1 (5.2%), D (1.6%) and Circulating Recombinant Forms (CRFs) (33.9%). CRF02_AG represented 72.3% of the total CRFs. Clusters between immigrants and Italian natives were also present. Drug resistance mutations to NRTI, NNRTI, and PI drug classes occurred in 29.1% of ART-treated and in 12.9% of ART-naïve individuals. These data highlight the need for tailored public health interventions in immigrants to avoid spreading in Italy of HIV genetic forms and ART-resistant variants, as well as HIV co-morbidities.
MeSH term(s)	Adult ; Antiretroviral Therapy, Highly Active ; Cluster Analysis ; Drug Resistance, Viral/genetics ; Emigrants and Immigrants ; Female ; Genetic Variation ; Geography ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; Humans ; Italy ; Male ; Middle Aged ; Mutation/genetics ; Phylogeny ; Recombination, Genetic/genetics
Language	English
Publishing date	2020-02-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-59084-2
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Article: A combination HIV vaccine based on Tat and Env proteins was immunogenic and protected macaques from mucosal SHIV challenge in a pilot study

Ferrantelli, Flavia / Maggiorella, Maria Teresa / Schiavoni, Ilaria / Sernicola, Leonardo / Olivieri, Erika / Farcomeni, Stefania / Pavone-Cossut, Maria Rosaria / Moretti, Sonia / Belli, Roberto / Collacchi, Barbara / Srivastava, Indresh K / Titti, Fausto / Cafaro, Aurelio / Barnett, Susan W / Ensoli, Barbara

Vaccine. 2011 Apr. 5, v. 29, no. 16

2011

Abstract: HIV native Tat and V2 loop-deleted Env (EnvΔV2) proteins already proved safe and immunogenic in phase I clinical testing as single vaccine components. Further, a phase II vaccine trial with Tat showed intensification of the therapeutic effects of HAART ... ...

Abstract	HIV native Tat and V2 loop-deleted Env (EnvΔV2) proteins already proved safe and immunogenic in phase I clinical testing as single vaccine components. Further, a phase II vaccine trial with Tat showed intensification of the therapeutic effects of HAART in successfully treated HIV-infected individuals. Here a pilot study assessed the immunogenicity and protective efficacy of an HIV/AIDS vaccine based on the combination of Tat and EnvΔV2 proteins in cynomolgus macaques against homologous intrarectal challenge with 35 MID₅₀ (monkey infectious dose 50) of an R5 simian-human immunodeficiency virus (SHIVSF₁₆₂P₄cy). Upon challenge, three of four macaques immunized with Tat and EnvΔV2, and two of three monkeys immunized with EnvΔV2 alone were protected from infection. In contrast, all three control animals, which had been either administered with the adjuvants only or left untreated, and an additional monkey immunized with Tat alone became systemically infected. Protection of the macaques vaccinated with EnvΔV2 or Tat/EnvΔV2 correlated with higher peak titers of pre-challenge neutralizing antibodies obtained during the immunization period (between 70 and 3weeks before challenge) and with anti-Env V3 loop binding antibodies assessed 3weeks before challenge. Compared to EnvΔV2 alone, the Tat and EnvΔV2 combined vaccine elicited faster antibody responses (IgM) with a trend, early in the vaccination schedule, after the second immunization including EnvΔV2, towards broader anti-Env IgG epitope specificity and a higher ratio of neutralizing to Env-binding antibody titers. As the number of immunizations increased, vaccination with EnvΔV2 approached the immune response assessed after two inocula with the Tat/EnvΔV2 combined vaccine, even though some differences remained between groups, as indicated by anti-Env IgG epitope mapping. In fact, three weeks before challenge, plasma IgG of animals in the EnvΔV2 group showed a trend towards stronger specificity for the V1 loop and V5 loop-C5 regions of Env, whereas the Tat/EnvΔV2 group displayed an overall higher reactivity for epitopes within the Env V3 loop throughout the immunization period. Although differences in terms of protection rate were not found between the EnvΔV2 or Tat/EnvΔV2 vaccination groups in this pilot study, vaccination with Tat/EnvΔV2 appeared to accelerate the induction of potentially protective antibody responses to Env. In particular, antibodies to the Env V3 loop, whose levels at pre-challenge correlated with protection, were already higher early in the vaccination schedule in monkeys immunized with Tat/EnvΔV2 as compared to EnvΔV2 alone. Further studies including larger vaccination groups and fewer immunizations with these two vaccine candidates are needed to confirm these findings and to assess whether the Tat/EnvΔV2 vaccine may afford superior protection against infection.
Keywords	HIV infections ; Lentivirus ; Macaca fascicularis ; adjuvants ; epitope mapping ; epitopes ; immune response ; immunoglobulin G ; immunoglobulin M ; monkeys ; neutralization ; neutralizing antibodies ; vaccination ; vaccines
Language	English
Dates of publication	2011-0405
Size	p. 2918-2932.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2011.02.006
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Article: Multiprotein genetic vaccine in the SIV-Macaca animal model: a promising approach to generate sterilizing immunity to HIV infection

Maggiorella, Maria Teresa / Sernicola, Leonardo / Crostarosa, Federica / Belli, Roberto / Pavone-Cossut, Maria Rosaria / Macchia, Iole / Farcomeni, Stefania / Tenner-Racz, Klara / Racz, Paul / Ensoli, Barbara / Titti, Fausto

Journal of medical primatology. 2007 Aug., v. 36, no. 4-5

2007

Abstract: Vaccine combining structural and regulatory proteins is an emerging approach to develop an HIV/AIDS vaccine and therefore, the immunogenicity and efficacy of two regimens of immunization combining structural (Gag/Pol, Env) and regulatory (Rev, Tat, Nef) ... ...

Abstract	Vaccine combining structural and regulatory proteins is an emerging approach to develop an HIV/AIDS vaccine and therefore, the immunogenicity and efficacy of two regimens of immunization combining structural (Gag/Pol, Env) and regulatory (Rev, Tat, Nef) Simian immunodeficiency virus (SIV) proteins were compared in cynomolgus monkeys. Monkeys were immunized with Modified Vaccine Ankara vector (MVA-J5) (protocol 1) or with DNA, Semliki forest virus and MVA vectors (DNA/SFV/MVA) (protocol 2). At week 32, all monkeys were challenge intravenously (protocol 1) or intrarectally (protocol 2) with 50 MID₅₀ of SIVmac251. Humoral, proliferative responses and in particular in protocol 2, the frequency of IFN-γ producing cells, were measured in all monkeys before and after the challenge. Both vaccine regimens elicited humoral and proliferative responses but failed to induce neutralizing antibodies. Upon intravenous challenge, two out of three MVA-J5 vaccinated monkeys exhibited a long-term control of the viral replication whereas DNA/SFV/MVA vaccine abrogated the virus replication up to undetectable level in three out of four vaccinated monkeys. A major contribution to this vaccine effect appeared to be the IFN-γ/ELISPOT responses to vaccine antigens (Gag, Rev Tat and Nef). These results, indicate that multiprotein heterologous prime-boost vaccination can induce a robust vaccine-induced immunity able to abrogate virus replication.
Keywords	DNA
Language	English
Dates of publication	2007-08
Size	p. 180-194.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	121206-0
ISSN	1600-0684 ; 0047-2565
ISSN (online)	1600-0684
ISSN	0047-2565
DOI	10.1111/j.1600-0684.2007.00236.x
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Zs.A 819: Show issues

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Article ; Online: Intratumoral injection of IFN-alpha dendritic cells after dacarbazine activates anti-tumor immunity: results from a phase I trial in advanced melanoma.

Rozera, Carmela / Cappellini, Giancarlo Antonini / D'Agostino, Giuseppina / Santodonato, Laura / Castiello, Luciano / Urbani, Francesca / Macchia, Iole / Aricò, Eleonora / Casorelli, Ida / Sestili, Paola / Montefiore, Enrica / Monque, Domenica / Carlei, Davide / Napolitano, Mariarosaria / Rizza, Paola / Moschella, Federica / Buccione, Carla / Belli, Roberto / Proietti, Enrico /

Pavan, Antonio / Marchetti, Paolo / Belardelli, Filippo / Capone, Imerio

Journal of translational medicine

2015 Volume 13, Page(s) 139

Abstract: Background: Advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies. The recently developed targeted therapies have resulted in a marked antitumor effect, but most responses are partial and some ... ...

Abstract	Background: Advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies. The recently developed targeted therapies have resulted in a marked antitumor effect, but most responses are partial and some degree of toxicity remain the major concerns. Dendritic cells play a key role in the activation of the immune system and have been typically used as ex vivo antigen-loaded cell drugs for cancer immunotherapy. Another approach consists in intratumoral injection of unloaded DCs that can exploit the uptake of a wider array of tumor-specific and individual unique antigens. However, intratumoral immunization requires DCs endowed at the same time with properties typically belonging to both immature and mature DCs (i.e. antigen uptake and T cell priming). DCs generated in presence of interferon-alpha (IFN-DCs), due to their features of partially mature DCs, capable of efficiently up-taking, processing and cross-presenting antigens to T cells, could successfully carry out this task. Combining intratumoral immunization with tumor-destructing therapies can induce antigen release in situ, facilitating the injected DCs in triggering an antitumor immune response. Methods: We tested in a phase I clinical study in advanced melanoma a chemo-immunotherapy approach based on unloaded IFN-DCs injected intratumorally one day after administration of dacarbazine. Primary endpoint of the study was treatment safety and tolerability. Secondary endpoints were immune and clinical responses of patients. Results: Six patients were enrolled, and only three completed the treatment. The chemo-immunotherapy was well tolerated with no major side effects. Three patients showed temporary disease stabilization and two of them showed induction of T cells specific for tyrosinase, NY-ESO-1 and gp100. Of interest, one patient showing a remarkable long-term disease stabilization kept showing presence of tyrosinase specific T cells in PBMC and high infiltration of memory T cells in the tumor lesion at 21 months. Conclusion: We tested a chemo-immunotherapeutic approach based on IFN-DCs injected intratumorally one day after DTIC in advanced melanoma. The treatment was well tolerated, and clinical and immunological responses, including development of vitiligo, were observed, therefore warranting additional clinical studies aimed at evaluating efficacy of this approach. Trial registration: Trial Registration Number not publicly available due to EudraCT regulations: https://www.clinicaltrialsregister.eu/doc/EU_CTR_FAQ.pdf.
MeSH term(s)	Adult ; Aged ; Antigens, Neoplasm/metabolism ; Cancer Vaccines/immunology ; Combined Modality Therapy/methods ; Dacarbazine/chemistry ; Dendritic Cells/cytology ; Drug Therapy/methods ; Female ; Gene Expression Profiling ; Humans ; Immunotherapy/methods ; Injections, Intralesional ; Interferon-alpha/metabolism ; Leukocytes, Mononuclear/cytology ; Male ; Melanoma/therapy ; Membrane Proteins/metabolism ; Microscopy, Confocal ; Middle Aged ; Monocytes/metabolism ; Monophenol Monooxygenase/metabolism ; Vitiligo/chemically induced ; gp100 Melanoma Antigen/metabolism
Chemical Substances	Antigens, Neoplasm ; CTAG1B protein, human ; Cancer Vaccines ; Interferon-alpha ; Membrane Proteins ; gp100 Melanoma Antigen ; Dacarbazine (7GR28W0FJI) ; Monophenol Monooxygenase (EC 1.14.18.1)
Language	English
Publishing date	2015-05-02
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-015-0473-5
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Article ; Online: Biocompatible anionic polymeric microspheres as priming delivery system for effetive HIV/AIDS Tat-based vaccines.

PloS one

2014 Volume 9, Issue 10, Page(s) e111360

Abstract: Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization ... ...

Abstract	Here we describe a prime-boost regimen of vaccination in Macaca fascicularis that combines priming with novel anionic microspheres designed to deliver the biologically active HIV-1 Tat protein and boosting with Tat in Alum. This regimen of immunization modulated the IgG subclass profile and elicited a balanced Th1-Th2 type of humoral and cellular responses. Remarkably, following intravenous challenge with SHIV89.6Pcy243, vaccinees significantly blunted acute viremia, as compared to control monkeys, and this control was associated with significantly lower CD4+ T cell depletion rate during the acute phase of infection and higher ability to resume the CD4+ T cell counts in the post-acute and chronic phases of infection. The long lasting control of viremia was associated with the persistence of high titers anti-Tat antibodies whose profile clearly distinguished vaccinees in controllers and viremics. Controllers, as opposed to vaccinated and viremic cynos, exhibited significantly higher pre-challenge antibody responses to peptides spanning the glutamine-rich and the RGD-integrin-binding regions of Tat. Finally, among vaccinees, titers of anti-Tat IgG1, IgG3 and IgG4 subclasses had a significant association with control of viremia in the acute and post-acute phases of infection. Altogether these findings indicate that the Tat/H1D/Alum regimen of immunization holds promise for next generation vaccines with Tat protein or other proteins for which maintenance of the native conformation and activity are critical for optimal immunogenicity. Our results also provide novel information on the role of anti-Tat responses in the prevention of HIV pathogenesis and for the design of new vaccine candidates.
MeSH term(s)	AIDS Vaccines/immunology ; Acquired Immunodeficiency Syndrome/blood ; Acquired Immunodeficiency Syndrome/immunology ; Acquired Immunodeficiency Syndrome/virology ; Animals ; Anions ; Antibody Formation/immunology ; Biocompatible Materials/chemistry ; CD4-Positive T-Lymphocytes/immunology ; Cross-Priming/immunology ; Cytokines/biosynthesis ; Drug Delivery Systems ; Epitope Mapping ; Immunity, Cellular/immunology ; Immunity, Humoral ; Immunization ; Immunoglobulin G/immunology ; Injections, Intravenous ; Lymphocyte Count ; Macaca ; Male ; Microspheres ; Polymers/chemistry ; Statistics, Nonparametric ; Viremia/blood ; Viremia/immunology ; tat Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; Anions ; Biocompatible Materials ; Cytokines ; Immunoglobulin G ; Polymers ; tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2014-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0111360
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Article ; Online: A combination HIV vaccine based on Tat and Env proteins was immunogenic and protected macaques from mucosal SHIV challenge in a pilot study.

Vaccine

2011 Volume 29, Issue 16, Page(s) 2918–2932

Abstract	HIV native Tat and V2 loop-deleted Env (EnvΔV2) proteins already proved safe and immunogenic in phase I clinical testing as single vaccine components. Further, a phase II vaccine trial with Tat showed intensification of the therapeutic effects of HAART in successfully treated HIV-infected individuals. Here a pilot study assessed the immunogenicity and protective efficacy of an HIV/AIDS vaccine based on the combination of Tat and EnvΔV2 proteins in cynomolgus macaques against homologous intrarectal challenge with 35 MID(50) (monkey infectious dose 50) of an R5 simian-human immunodeficiency virus (SHIV(SF162P4cy)). Upon challenge, three of four macaques immunized with Tat and EnvΔV2, and two of three monkeys immunized with EnvΔV2 alone were protected from infection. In contrast, all three control animals, which had been either administered with the adjuvants only or left untreated, and an additional monkey immunized with Tat alone became systemically infected. Protection of the macaques vaccinated with EnvΔV2 or Tat/EnvΔV2 correlated with higher peak titers of pre-challenge neutralizing antibodies obtained during the immunization period (between 70 and 3 weeks before challenge) and with anti-Env V3 loop binding antibodies assessed 3 weeks before challenge. Compared to EnvΔV2 alone, the Tat and EnvΔV2 combined vaccine elicited faster antibody responses (IgM) with a trend, early in the vaccination schedule, after the second immunization including EnvΔV2, towards broader anti-Env IgG epitope specificity and a higher ratio of neutralizing to Env-binding antibody titers. As the number of immunizations increased, vaccination with EnvΔV2 approached the immune response assessed after two inocula with the Tat/EnvΔV2 combined vaccine, even though some differences remained between groups, as indicated by anti-Env IgG epitope mapping. In fact, three weeks before challenge, plasma IgG of animals in the EnvΔV2 group showed a trend towards stronger specificity for the V1 loop and V5 loop-C5 regions of Env, whereas the Tat/EnvΔV2 group displayed an overall higher reactivity for epitopes within the Env V3 loop throughout the immunization period. Although differences in terms of protection rate were not found between the EnvΔV2 or Tat/EnvΔV2 vaccination groups in this pilot study, vaccination with Tat/EnvΔV2 appeared to accelerate the induction of potentially protective antibody responses to Env. In particular, antibodies to the Env V3 loop, whose levels at pre-challenge correlated with protection, were already higher early in the vaccination schedule in monkeys immunized with Tat/EnvΔV2 as compared to EnvΔV2 alone. Further studies including larger vaccination groups and fewer immunizations with these two vaccine candidates are needed to confirm these findings and to assess whether the Tat/EnvΔV2 vaccine may afford superior protection against infection.
MeSH term(s)	AIDS Vaccines/genetics ; AIDS Vaccines/immunology ; Adjuvants, Immunologic/administration & dosage ; Animals ; Antibodies, Neutralizing/blood ; Antibody Formation ; Epitope Mapping ; HIV Antibodies/blood ; HIV Infections/immunology ; HIV Infections/prevention & control ; Immunity, Cellular ; Macaca fascicularis ; Male ; Pilot Projects ; RNA, Viral/blood ; env Gene Products, Human Immunodeficiency Virus/immunology ; tat Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; Adjuvants, Immunologic ; Antibodies, Neutralizing ; HIV Antibodies ; RNA, Viral ; env Gene Products, Human Immunodeficiency Virus ; tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2011-04-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2011.02.006
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