The effect of smallpox and BCG vaccination on the risk of HIV-1 infection in Guinea-Bissau and Denmark | Open Forum Infectious Diseases | Oxford Academic

Background:
The live smallpox and BCG vaccinations have been associated with better adult survival in both Guinea-Bissau and Denmark. In Guinea-Bissau, HIV-1 became an important cause of death after smallpox vaccination was phased out globally in 1980. We hypothesised that smallpox and BCG vaccinations were associated with a lower prevalence of HIV-1 infection, and tested this hypothesis both in Guinea-Bissau and in Denmark.

Methods:
We conducted two studies, a cross-sectional study of HIV infection and vaccination scars in Guinea-Bissau including 1,751 individuals, and a case-base study with a background population of 46,239 individuals in Denmark. In Guinea-Bissau, HIV-1 transmission is almost exclusively sexually transmitted, in Denmark we excluded intravenous drug users. Data was analysed using logistic regression.

Results:
BCG and/or smallpox vaccination compared with neither of these vaccines was associated with an adjusted odds ratio (aOR) for HIV-1 of 0.62 (95% confidence interval (CI) 0.36-1.07) in Guinea-Bissau and 0.70 (95%CI 0.43-1.15) in Denmark. Combining results from both settings in a meta-analysis gave an aOR of 0.66 (95%CI 0.46-0.96). Data from Guinea-Bissau indicated a stronger effect of multiple smallpox vaccination scars (aOR of 0.27 (95%CI 0.10-0.75); women: 0.18 (95%CI 0.05-0.64), men: 0.52 (95%CI 0.12-2.33), sex-differential effect, p-value = 0.29).


Conclusions:
The studies from Guinea-Bissau and Denmark, two very different settings, both suggest that the BCG and smallpox vaccines could be associated with a decreased risk of sexually transmitted HIV-1. It might be informative to pursue this observation and explore possible protective mechanisms as part of the search for an HIV-1 vaccine."

Related:- Cowpox Helped Against Smallpox; Will the Goat Lentivirus (Caprine Arthritis Encephalitis Virus) Help Against HIV-1?

Vaccinia and other viruses with available vaccines show marked homology with the HIV-1 envelope glycoprotein: the prospect of using existing vaccines to stem the AIDS pandemic.

RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection

For more than three decades since the discovery of HIV-1, AIDS remains a major public health problem affecting greater than 35.3 million people worldwide. Current antiretroviral therapy has failed to eradicate HIV-1, partly due to the persistence of viral reservoirs. RNA-guided HIV-1 genome cleavage by the Cas9 technology has shown promising efficacy in disrupting the HIV-1 genome in latently infected cells, suppressing viral gene expression and replication, and immunizing uninfected cells against HIV-1 infection. These properties may provide a viable path toward a permanent cure for AIDS, and provide a means to vaccinate against other pathogenic viruses. Given the ease and rapidity of Cas9/guide RNA development, personalized therapies for individual patients with HIV-1 variants can be developed instantly.

BBC News - Immune upgrade with CCR5 delta gives 'HIV shielding'

researchers at the University of Pennsylvania are adapting patients' own immune systems to give them the defence offered by the CCR5 delta chemokine receptor .
Millions of T-cells were taken from the blood and grown in the laboratory until the doctors had billions of cells to play with.
The team then edited the DNA inside the T-cells to give them the shielding mutation - known as CCR5-delta-32.
About 10 billion cells were then infused back in, although only around 20% were successfully modified.
When patients were taken off their medication for four weeks, the number of unprotected T-cells still in the body fell dramatically, whereas the modified T-cells seemed to be protected and could still be found in the blood several months later.

PLOS Pathogens: Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART

Antiretroviral therapy (ART) can reduce HIV levels in plasma to undetectable levels, but rather little is known about the effects of ART outside of the peripheral blood regarding persistent virus production in tissue reservoirs. Understanding the dynamics of ART-induced reductions in viral RNA (vRNA) levels throughout the body is important for the development of strategies to eradicate infectious HIV from patients. Essential to a successful eradication therapy is a component capable of killing persisting HIV infected cells during ART. Therefore, we determined the in vivo efficacy of a targeted cytotoxic therapy to kill infected cells that persist despite long-term ART. For this purpose, we first characterized the impact of ART on HIV RNA levels in multiple organs of bone marrow-liver-thymus (BLT) humanized mice and found that antiretroviral drug penetration and activity was sufficient to reduce, but not eliminate, HIV production in each tissue tested. For targeted cytotoxic killing of these persistent vRNA⁺ cells, we treated BLT mice undergoing ART with an HIV-specific immunotoxin. We found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. These results offer proof-of-concept that targeted cytotoxic therapies can be effective components of HIV eradication strategies.

Geneticists map human resistance to HIV

  "The key to future HIV treatment could be hidden right in our own genes. Everyone who becomes infected deploys defense strategies, and some even manage to hold the virus at bay without any therapy at all. This immune system struggle leaves its mark within the pathogen itself – genetic mutations that indicate how the virus reacted to its host's attacks. Scientists from EPFL and the Vaud university hospital center (UNIL-CHUV) retraced the entire chain of events in these battles, from the genome of the virus to the genome of the victim. They have created the first map of human HIV resistance. The goal of their research, which has been published in the journal eLife on the 29th of October, is to find new therapeutic targets and to enable individualized treatment strategies."

Compounds That Stimulate The Cannabinoid Type 2 Receptor In White Blood Cells Can Weaken HIV-1 Infection

MNT "A new use for compounds related in composition to the active ingredient in marijuana may be on the horizon: a new research report published in the Journal of Leukocyte Biology shows that compounds that stimulate the cannabinoid type 2 (CB2) receptor in white blood cells, specifically macrophages, appear to weaken HIV-1 infection. The CB2 receptor is one of the  the molecular links through which the pharmaceutical properties of cannabis are manifested. "

Futurity.org – To harness HIV, make it get ‘naked’

"EMORY (US) — A new understanding of how HIV “gets dressed” in the human cells it has taken over could lead to new antiretroviral drugs, researchers say."

Rab11-FIP1C and Rab14 Direct Plasma Membrane Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex PLOS PATHOGENS

BBC News - Body's anti-HIV 'training manual' offers vaccine hopes

The body's own "training manual" for successfully attacking HIV has been recorded by scientists and it is hoped it can be used to design vaccines.

Innate immune system can kill HIV when a viral gene is deactivated

 "A family of human proteins called APOBEC3 effectively restrict the growth of HIV and other viruses, but this action is fully counteracted by the viral infectivity factor gene (vif) in HIV. In the study, researchers intravenously infected humanized mice with HIV. They found that the most commonly transmitted strains of HIV are completely neutralized by APOBEC3 proteins when vif is removed from the virus.
"Without the vif gene, HIV can be completely destroyed by the body's own immune system," said J. Victor Garcia, PhD, professor of medicine at the UNC School of Medicine and senior author on the study. "These results suggest a new target for developing drugs fully capable of killing the virus.""

A 'Neurosteroid' Found To Prevent Brain Injury Caused By HIV/AIDS

MNT: A team of scientists from Canada, Thailand and Morocco have found that DHEA-S may prevent neurocognitive impairment that affects a significant percentage of AIDS patients. In a report appearing in the February 2013 issue of The FASEB Journal, they describe how a network of steroid molecules found in the brain, termed "neurosteroids," is disrupted during HIVinfection leading to brain damage. This suggests that treatment with one of these steroid molecules, called DHEA-S, may offset the disruption caused by the virus to prevent or reduce brain damage. 

Australian scientists may have found ‘potential cure for Aids’ Microbe World

A FORM of gene therapy developed by researchers at the Queensland Institute of Medical Research may provide hope to sufferers of HIV, preventing the virus from crippling the immune system by manipulating its genetic structure and turning HIV into a weapon against itself.

BMC Evolutionary Biology | Abstract | Evidence for selection at HIV host susceptibility genes in a West Central African human population

HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1.

Results

SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding.

Conclusions

We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.

AIDS Vaccine Clue In Discovery Of HIV Vulnerable Spot: MNT

Researchers in South Africa leading a study published recently, suggest their findings offer a new clue toward a possible vaccine against AIDS. They have discovered a vulnerable spot on the outer shell of the human immunodeficiency virus (HIV) that enabled two infected people to make antibodies powerful enough to kill most of the HIV types known around the world.

Cheap, Ultra-Sensitive Colour Test Spots Early HIV, Cancer

Researchers in the UK have developed a "naked eye" colour test for virus and disease biomarkers that is ten times more sensitive than current gold standard methods. They have tested it on HIV and prostate cancer biomarkers, and suggest it offers a cheap and simple way of spotting early onset of these and other diseases that could be of particular benefit in poorer countries.

Common Transcriptional Signatures in Brain Tissue from Patients with HIV-Associated Neurocognitive Disorders, Alzheimer's Disease, and Multiple Sclerosis.

HIV-Associated Neurocognitive Disorders (HAND) is a common manifestation of HIV infection that afflicts about 50 % of HIV-positive individuals. As people with access to antiretroviral treatments live longer, HAND can be found in increasing segments of populations at risk for other chronic, neurodegenerative conditions such as Alzheimer's disease (AD) and Multiple Sclerosis (MS). If brain diseases of diverse etiologies utilize similar biological pathways in the brain, they may coexist in a patient and possibly exacerbate neuropathogenesis and morbidity. To test this proposition, we conducted comparative meta-analysis of selected publicly available microarray datasets from brain tissues of patients with HAND, AD, and MS. In pair-wise and three-way analyses, we found a large number of dysregulated genes and biological processes common to either HAND and AD or HAND and MS, or to all three diseases. The common characteristic of all three diseases was up-regulation of broadly ranging immune responses in the brain. In addition, HAND and AD share down-modulation of processes involved, among others, in synaptic transmission and cell-cell signaling while HAND and MS share defective processes of neurogenesis and calcium/calmodulin-dependent protein kinase activity. Our approach could provide insight into the identification of common disease mechanisms and better intervention strategies for complex neurocognitive disorders.

New Clue To Slower Progression Of AIDS: MNT

The average time from HIV infection to full-blown AIDS in the absence of treatment is about 10 years, and while some people succumb much sooner, others, known as the "slow progressors", can remain healthy for another 20 years or more. Now scientists at the University of California, Los Angeles (UCLA), believe they may have uncovered a new clue as to why.

Anti-interferon-gamma autoantibodies cause adult-onset immunodeficiency disease similar to patients with advanced HIV infection | The Virology Hub

Work by Browne, S. K. et al (2012) showed that anti–interferon (IFN)-gamma autoantibodies found in a group of Asian adults with disseminated nontuberculous mycobacterial infection, alone or with another opportunistic infection, had an adult-onset immunodeficiency disease similar in nature to that seen in patients with advanced HIV infection. The cause of the anti-interferon-gamma autoantibodies appeared unrelated to a singular genetic predisposition and the authors speculate that an environmental factor or opportunistic infection could be the trigger.

Discovery of new white blood cell reveals target for better vaccine design

Researchers in Newcastle and Singapore have identified a new type of white blood cell which activates a killing immune response to an external source -- providing a new potential target for vaccines for conditions such as cancer or Hepatitis B.

Protein Starves HIV, Thus Protecting Cells

Medical News Today: A protein called SAMHD1 has been found to starve HIV in cells so that it cannot do anything, thus making the cell resistant to HIV infection, researchers at NYU Langone Medical Center reported in Nature Immunology. The authors explained that their discovery could pave the way for new therapeutic research at halting or slowing the HIV's progression to AIDS.