Long-term protective immunity induced by an adjuvant-containing live-attenuated AIDS virus

The use of an adjuvant in vaccination is thought to be effective for enhancing immune responses to various pathogens. We genetically constructed a live attenuated simian human immunodeficiency virus (SHIV) to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When the macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B had become undetectable, SHIV89.6P was not detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of the pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.

PREVENÇÃO DE INFECÇÕES SEXUALMENTE TRANSMISSÍVEIS

As Infecções Sexualmente Transmissíveis (IST) estão entre os problemas de saúde pública mais comuns em todo o mundo. O termo Infecções Sexualmente Transmissíveis passou a ser adotado em substituição à expressão Doenças Sexualmente Transmissível (DST), para destacar a possibilidade de uma pessoa sem sinais e sintomas ter uma infecção e transmitir. Dentre as IST, as mais comuns são: sífilis, gonorreia, HPV (papilomavírus humano), herpes simples, tricomoníase, candidíase, gardnerella, hepatite B e C, e HIV/Aids (Vírus da Imunodeficiência Humana/síndrome da imunodeficiência adquirida). Ainda, outras infecções como hepatite A e amebíase são importantes entre LGBTI+ por terem transmissão por meio da prática de sexo oral-anal.

Pandemic Sociology

In 1990, the sociologist Phil Strong wrote about “epidemic psychology” as part of his research on the recent history of AIDS. Strong described vividly how epidemics of fear, of explanation and moralization, and of (proposed) action accompanied the epidemic of the AIDS virus per se. In this essay, I draw on these formulations to think through the current COVID-19 crisis, illustrating too a pandemic of inequality. In so doing, I provide a sketch of a pandemic sociology.

Long-term sterile immunity induced by an adjuvant-containing live-attenuated AIDS virus

Antigen 85B (Ag85B) is one of the most dominant proteins secreted from most mycobacterial species, and it induces Th1-type immune responses as an adjuvant. We genetically constructed a live attenuated simian human immunodeficiency virus to express the adjuvant molecule Ag85B (SHIV-Ag85B). SHIV-Ag85B could not be detected 4 weeks after injection in cynomolgus macaques, and strong SHIV-specific T cell responses were induced in these macaques. When these macaques in which SHIV-Ag85B had become undetectable were challenged with pathogenic SHIV89.6P at 37 weeks after SHIV-Ag85B became undetectable, SHIV89.6P could not be detected after the challenge. Eradication of SHIV89.6P was confirmed by adoptive transfer experiments and CD8-depletion studies. The SHIV-Ag85B-inoculated macaques showed enhancement of Gag-specific monofunctional and polyfunctional CD8+ T cells in the acute phase of pathogenic SHIV challenge. The results suggest that SHIV-Ag85B elicited strong sterile immune responses against pathogenic SHIV and that it may lead to the development of a vaccine for AIDS virus infection.ImportanceDevelopment of an effective HIV vaccine has been a major priority to control the worldwide AIDS epidemic. The moderately attenuated prototypic vaccine strain SIVmac239Δnef has been used in various studies; however, it does not provide sufficient effects to prevent infection. The use of adjuvant in vaccination is thought to be useful for enhancing the immune responses to various pathogens. In the present study, we constructed a live attenuated SHIV virus expressing adjuvant molecule Ag85B and assessed vaccine effects in cynomolgus macaques. The present study shows that live-attenuated SHIV expressing Ag85B elicits viral antigen-specific polyfunctional CD8+ T cell responses against pathogenic SHIV and provide the possibility of eradicating a pathogenic lentivirus from infected animals.

Implementation of the Methadone Maintenance Therapy Program for Highrisk Drug Prisoners

<p>The harm reduction program is a program that aims to assist inmates who use syringes (IDU's) in overcoming dependence on narcotics medically and to prevent the adverse effects caused by narcotics abuse. Where in general the use of heroin is done by injecting using a syringe alternately, or known as "For Wet" This can cause a new problem that is greater that the outbreak of the HIV/AIDS virus. Most prisoners use injecting narcotics before entering prison and have been infected with the HIV virus, so the risk of transmitting HIV/AIDS to other prisoners is very high. The tendency of the number of relapses (reuse) by prisoners who are in the period of coaching is quite high despite the efforts of strict supervision in the security sector, but in fact in several prisons/detention there is narcotics smuggling in various modes. For this reason, the Indonesian Ministry of Law and Human Rights through the Directorate General of Corrections organizes the P4GN program (Prevention of Eradication of Narcotics Abuse and Circulation) in prisons and detention environments by promoting the principle of "Total Abstinence" meaning that no use of any type of narcotics during coaching in prisons and prisons. But for the type of metadone, which is a type II narcotics can be tolerated because it is used for the purpose of treatment/healing of narcotics dependence and is also a government program implemented by the Ministry of Health as the leading sector.</p>

RUMAH REHABILITASI ODHA (ORANG DENGAN HIV/AIDS)

HIV / AIDS is the most dangerous virus in the world that can be transmitted. People infected with this disease are called ODHA. At present they are not only fighting against the disease but they are also fighting against the bad stigma in society. With this negative stigma, ODHA are easily depressed and many ODHA choose to end their lives. For this reason, a rehabilitation center is needed to improve the standard of living for ODHA and the place of education for the HIV virus so that the stigma gradually diminishes. From studying the theory of the development of hospital typologies and the HIV / AIDS virus obtained a design method such as a). The hospital is open to the public, b). Sunlight affects the patient's mental and physical development, c). The circulation pattern of the hospital is in the form of aisle, d). Patients and the public can be combined if the disease is not contagious. In conclusion, the existence of a passage that can be traversed by the public and a program that triggers interaction between building users is expected to reduce the stigma of society and become a therapy for ODHA. So that ODHA have a strong mental life and will live their lives like Non-ODHA. Abstrak HIV/ AIDS adalah virus yang paling berbahaya didunia yang dapat menular. Orang yang terinfeksi dengan penyakit ini disebut ODHA. Saat ini mereka tidak hanya berperang melawan penyakitnya namun mereka juga berperang melawan stigma buruk pada masyarakat. Dengan adanya stigma negatif tersebut membuat ODHA mudah mengalami depresi dan bahkan banyak dari ODHA memilih untuk mengakhiri hidupnya. Untuk itu diperlukannya suatu wadah rehabilitasi agar meningkatkan taraf hidup ODHA dan wadah pendidikan virus HIV agar stigma tersebut lambat laun berkurang. Dari mempelajari teori perkembangan tipologi rumah sakit dan virus HIV/ AIDS didapatkan suatu metode perancangan seperti a). Rumah sakit terbuka untuk publik, b). Cahaya matahari memengaruhi perkembangan secara mental dan jasmani pasien, c). Pola sirkulasi rumah sakit berbentuk lorong, d). Pasien dan publik dapat digabung jika penyakit tidak menular. Kesimpulannya dengan adanya passage yang dapat dilalui publik dan program yang memicu interaksi antar pengguna bangunan diharapkan stigma buruk pada masyarakat berkurang dan menjadi terapi bagi ODHA. Sehingga para ODHA memiliki mental hidup yang kuat dan akan menjalani hidupnya layaknya Non-ODHA.

Preferential Small Intestine Homing and Persistence of CD8 T Cells in Rhesus Macaques Achieved by Molecularly Engineered Expression of CCR9 and Reduced Ex Vivo Manipulation

ABSTRACT Adoptive cell transfer (ACT) is a powerful experimental approach to directly study T-cell-mediated immunity in vivo. In the rhesus macaque AIDS virus model, infusing simian immunodeficiency virus (SIV)-infected animals with CD8 T cells engineered to express anti-SIV T-cell receptor specificities enables direct experimentation to better understand antiviral T-cell immunity in vivo. Limiting factors in ACT experiments include suboptimal trafficking to, and poor persistence in, the secondary lymphoid tissues targeted by AIDS viruses. Previously, we redirected CD8 T cells to B-cell follicles by ectopic expression of the CXCR5 homing protein. Here, we modify peripheral blood mononuclear cell (PBMC)-derived CD8 T cells to express the CCR9 chemokine receptor, which induces preferential homing of the engineered cells to the small intestine, a site of intense early AIDS virus replication and pathology in rhesus macaques. Additionally, we increase in vivo persistence and overall systemic distribution of infused CD8 T cells, especially in secondary lymphoid tissues, by minimizing ex vivo culture/manipulation, thereby avoiding the loss of CD28+/CD95+ central memory T cells by differentiation in culture. These proof-of-principle results establish the feasibility of preferentially localizing PBMC-derived CD8 T cells to the small intestine and enables the direct experimental ACT-based assessment of the potential role of the quality and timing of effective antiviral CD8 T-cell responses to inhibit viral infection and subsequent replication in small intestine CD4 T cells. More broadly, these results support the engineered expression of homing proteins to direct CD8 T cells to target tissues as a means for both experimental and potential therapeutic advances in T-cell immunotherapies, including cancer. IMPORTANCE Adoptive cell transfer (ACT) of T cells engineered with antigen-specific effector properties can deliver targeted immune responses against malignancies and infectious diseases. Current T-cell-based therapeutic ACT relies on circulatory distribution to deliver engineered T cells to their targets, an approach which has proven effective for some leukemias but provided only limited efficacy against solid tumors. Here, engineered expression of the CCR9 homing receptor redirected CD8 T cells to the small intestine in rhesus macaque ACT experiments. Targeted homing of engineered T-cell immunotherapies holds promise to increase the effectiveness of adoptively transferred cells in both experimental and clinical settings.

Ferments and the AIDS virus: interspecies counter-conduct in the history of AIDS

In the first three decades after AIDS started infecting people in the USA and Canada, before, during and after the emergence of anti-retroviral therapies, numerous “alternative and holistic treatments” for AIDS were debated, tested, circulated, written about and taught. This paper, taking a narrow focus, examines documents that reveal how some people with AIDS developed a logic of care predicated on intimate interactions with microscopic lifeforms—the AIDS virus and the bacteria involved in fermentation, in particular. Focusing on the writings of Jon Greenberg and Sandor Katz, two former members of ACT UP/NY, I show that the men did not just dissent from management by biomedical authority but found new authority about how to care for themselves as people with AIDS from their interactions with non-human microscopic life. The practices and writings of both men demonstrate that Foucault’s theory of counter-conduct exists in the history of AIDS as an interspecies process in which microscopic existents lead humans. From Katz and Greenberg, I argue there is an interspecies dimension to counter-conduct that exists as a frame for understanding people who find in non-human life a guide towards unconventional forms of care, revised forms of human behaviour and philosophies for persisting with illness.