Showing posts with label antibody. Show all posts
Showing posts with label antibody. Show all posts

Wednesday, July 23, 2025

Gilead’s Long Standing Commitment To Help End The HIV Epidemic

In June 1981, news of a mysterious disease first began making headlines out of San Francisco, Los Angeles and New York. People who were impacted developed unusual infections and grew sick as their immune systems failed. Those early days of what we now know as the HIV epidemic were marked by great fear and loss. By the time the first medicine was introduced in the United States in 1987, more than 5,000 people had died and the number of people impacted continued to balloon……..Continue reading….

By: Gilead Sciences

Source: 3BL

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Critics:

Many HIV-positive people are unaware that they are infected with the virus. For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results. Again, this proportion is even lower in rural health facilities.

Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV. HIV-1 testing is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate.

If the result of either duplicate test is reactive, the specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection.

Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person. Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results.

Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations. In addition, a few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection. Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time.

The chance of a false-positive result in a standard two-step testing protocol is estimated to be about 1 in 250,000 in a low risk population. Testing post-exposure is recommended immediately and then at six weeks, three months, and six months. HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.

Many governments and research institutions participate in HIV/AIDS research. This research includes behavioral health interventions, such as research into sex education, and drug development, such as research into microbicides for sexually transmitted diseases, HIV vaccines, and anti-retroviral drugs. Other medical research areas include the topics of pre-exposure prophylaxis, post-exposure prophylaxis, circumcision, and accelerated aging effects.

The management of HIV/AIDS typically involves the use of multiple antiretroviral drugs. In many parts of the world, HIV has become a chronic condition, with progression to AIDS increasingly rare. HIV latency and the resulting viral reservoir in CD4+ T cells, dendritic cells, and macrophages is the main barrier to eradication of the virus. While HIV is highly virulent, transmission through sexual contact does not occur when an HIV-positive individual maintains a consistently undetectable viral load (<50 copies/ml) due to antiretroviral treatment.

This concept was first proposed by the Swiss Federal Commission for AIDS/HIV in 2008 in what is known as the Swiss Statement. Although initially controversial, subsequent studies have confirmed that the risk of transmitting HIV through sex is effectively zero when the HIV-positive person has a consistently undetectable viral load, a concept now widely known as U=U, or “Undetectable = Untransmittable.

In 1983, two separate research groups led by American Robert Gallo and French investigators Françoise Barré-Sinoussi and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same issue of the journal Science. Gallo claimed that a virus his group had isolated from a person with AIDS was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) his group had been the first to isolate.

Gallo admitted in 1987 that the virus he claimed to have discovered in 1984 was in reality a virus sent to him from France the year before.[170] Gallo’s group called their newly isolated virus HTLV-III. Montagnier’s group isolated a virus from a patient presenting with swelling of the lymph nodes of the neck and physical weakness, two classic symptoms of primary HIV infection. Contradicting the report from Gallo’s group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I.

Montagnier’s group named their isolated virus lymphadenopathy-associated virus (LAV). As these two viruses turned out to be the same, in 1986 LAV and HTLV-III were renamed HIV. Another group working contemporaneously with the Montagnier and Gallo groups was that of Jay A. Levy at the University of California, San Francisco. He independently discovered the AIDS virus in 1983 and named it the AIDS associated retrovirus (ARV).

This virus was very different from the virus reported by the Montagnier and Gallo groups. The ARV strains indicated, for the first time, the heterogeneity of HIV isolates and several of these remain classic examples of the AIDS virus found in the United States.

Emerging Concepts in the Immunopathogenesis of AIDS”

Opportunistic Infections in HIV-Infected Patients Differ Strongly in Frequencies and Spectra between Patients with Low CD4+ Cell Counts Examined Postmortem and Compensated Patients Examined Antemortem Irrespective of the HAART Era”2007 AIDS epidemic update”

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study”

HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads”

Contaminants in human milk: weighing the risks against the benefits of breastfeeding”public domain

Preventing Mother-to-Child Transmission of HIV”

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection”

HIV-1 induced bystander apoptosis”

Robbins Basic Pathology 

International Committee on Taxonomy of Viruses

HIV latency”

Human Immunodeficiency Virus Type 2″

HIV Sequence Compendium 2008 Introduction 

Core structure of gp41 from the HIV envelope glycoprotein” 

Few and far between: how HIV may be evading antibody avidity”

Crystal structure of key HIV protein reveals new prevention, treatment targets” 

Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein”

Glycan clustering stabilizes the mannose patch of HIV-1 and preserves vulnerability to broadly neutralizing antibodies”.

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Labels:hiv,aids,antibody,protein,medicalnews,gilead,medicine,glycoprotein,commitement,epidemic,infection,disease,immunesystem

 

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Tuesday, July 1, 2025

Study Suggests COVID19 Infection No Longer Grants Long Lasting Immunity

kjpargeter on Freepik

In the height of the COVID-19 pandemic, the only comfort from seeing those two lines pop up on a rapid test confirming infection was that at least you’d be insulated from reinfection for quite a while. A study in Nature, however, has found that since Omicron hit in late 2021, there is effectively no such thing as long-lasting natural immunity to COVID-19…….Continue reading….

By: Priya Joi

Source: Gavi

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Critics:

Several COVID‑19 vaccines, such as the Pfizer BioNTech and Moderna vaccines, use RNA to stimulate an immune response. When introduced into human tissue, the vaccine contains either self-replicating RNA or messenger RNA (mRNA), which both cause cells to express the SARS-CoV-2 spike protein. This teaches the body how to identify and destroy the corresponding pathogen.

RNA vaccines often use nucleoside-modified messenger RNA. The delivery of mRNA is achieved by a coformulation of the molecule into lipid nanoparticles, which protect the RNA strands and help their absorption into the cells. RNA vaccines are the first COVID‑19 vaccines to be authorized in the United Kingdom, the United States, and the European Union. Authorized vaccines of this type include the Pfizer–BioNTech and Moderna vaccines.

The CVnCoV RNA vaccine from CureVac failed in clinical trials. Severe allergic reactions are rare. In December 2020, 1,893,360 first doses of Pfizer–BioNTech COVID‑19 vaccine administration resulted in 175 cases of severe allergic reactions, of which 21 were anaphylaxis. For 4,041,396 Moderna COVID‑19 vaccine dose administrations in December 2020 and January 2021, only ten cases of anaphylaxis were reported. Lipid nanoparticles (LNPs) were most likely responsible for the allergic reactions.

These vaccines are examples of non-replicating viral vector vaccines using an adenovirus shell containing DNA that encodes a SARS‑CoV‑2 protein. The viral vector-based vaccines against COVID‑19 are non-replicating, meaning that they do not make new virus particles but rather produce only the antigen that elicits a systemic immune response. Authorized vaccines of this type include the Oxford–AstraZeneca COVID‑19 vaccine, the Sputnik V COVID‑19 vaccine, Convidecia, and the Janssen COVID‑19 vaccine.

Convidecia and Janssen are both one-shot vaccines that offer less complicated logistics and can be stored under ordinary refrigeration for several months. Sputnik V uses Ad26 for its first dose, which is the same as Janssen’s only dose, and Ad5 for the second dose, which is the same as Convidecia’s only dose. In August 2021, the developers of Sputnik V proposed, in view of the Delta case surge, that Pfizer test the Ad26 component (termed its ‘Light’ version) as a booster shot.

Inactivated vaccines consist of virus particles that are grown in culture and then killed using a method such as heat or formaldehyde to lose disease-producing capacity while still stimulating an immune response. Inactivated virus vaccines authorized in China include the Chinese CoronaVac and the Sinopharm BIBP and WIBP vaccines; there is also the Indian Covaxin, the Russian CoviVac, the Kazakh vaccine QazVac,and the Iranian COVIran Barekat.Vaccines in clinical trials include the Valneva COVID‑19 vaccine.

Subunit vaccines present one or more antigens without introducing whole pathogen particles. The antigens involved are often protein subunits, but they can be any molecule fragment of the pathogen. The authorized vaccines of this type include the peptide vaccine EpiVacCorona, ZF2001, MVC-COV1901, Corbevax,the Sanofi–GSK vaccine, and Soberana 02 (a conjugate vaccine). Bimervax (selvacovatein) was approved for use as a booster vaccine in the European Union in March 2023.

The V451 vaccine was in clinical trials that were terminated after it was found that the vaccine may potentially cause incorrect results for subsequent HIV testing. The authorized vaccines of this type include the Novavax COVID‑19 vaccine. Additional types of vaccines that are in clinical trials include multiple DNA plasmid vaccines,at least two lentivirus vector vaccines, a conjugate vaccine, and a vesicular stomatitis virus displaying the SARS‑CoV‑2 spike protein.

These vaccines are designed to stimulate nasal immune factors, such as IgA. In addition to inhibiting the virus, nasal vaccines provide ease of administration because no needles (or needle phobia) are involved. A variety of intranasal COVID‑19 vaccines are undergoing clinical trials. The first authorised intranasal vaccine was Razi Cov Pars in Iran at the end of October 2021. The first viral component of Sputnik V vaccine was authorised in Russia as Sputnik Nasal in April 2022.

 In September 2022, India and China approved two nasal COVID‑19 vaccines (iNCOVACC and Convidecia), which may (as boosters)also reduce transmission (potentially via sterilizing immunity). In December 2022, China approved a second intranasal vaccine as a booster, trade name Pneucolin. Aivita Biomedical is developing an experimental autologous dendritic cell COVID‑19 vaccine kit where the vaccine is prepared and incubated at the point-of-care using cells from the intended recipient.The vaccine is undergoing small phase I and phase II clinical studies.

A universal coronavirus vaccine would be effective against all coronaviruses and possibly other viruses. The concept was publicly endorsed by NIAID director Anthony Fauci, virologist Jeffery K. Taubenberger, and David M. Morens. In March 2022, the White House released the “National COVID‑19 Preparedness Plan”, which recommended accelerating the development of a universal coronavirus vaccine. One attempt at such a vaccine is being developed at the Walter Reed Army Institute of Research. It uses a spike ferritin-based nanoparticle (SpFN). This vaccine began a Phase I clinical trial in April 2022.

 Results of this trial were published in May 2024. Other universal vaccines that have entered clinical trial include OVX033 (France),PanCov (France),pEVAC-PS (UK),and VBI-2902 (Canada). Another strategy is to attach vaccine fragments from multiple strains to a nanoparticle scaffold. One theory is that a broader range of strains can be vaccinated against by targeting the receptor-binding domain, rather than the whole spike protein.

As of September 2020, eleven of the vaccine candidates in clinical development use adjuvants to enhance immunogenicity. An immunological adjuvant is a substance formulated with a vaccine to elevate the immune response to an antigen, such as the COVID‑19 virus or influenza virus. Specifically, an adjuvant may be used in formulating a COVID‑19 vaccine candidate to boost its immunogenicity and efficacy to reduce or prevent COVID‑19 infection in vaccinated individuals.

Adjuvants used in COVID‑19 vaccine formulation may be particularly effective for technologies using the inactivated COVID‑19 virus and recombinant protein-based or vector-based vaccines.Aluminum salts, known as “alum”, were the first adjuvant used for licensed vaccines and are the adjuvant of choice in some 80% of adjuvanted vaccines.The alum adjuvant initiates diverse molecular and cellular mechanisms to enhance immunogenicity, including the release of proinflammatory cytokines.

In June 2024, the US Food and Drug Administration (FDA) advised the manufacturers of the licensed and authorized COVID-19 vaccines that the COVID-19 vaccines (2024-2025 Formula) for use in the United States beginning in fall 2024 should be monovalent JN.1 vaccines. Since January 2020, vaccine development has been expedited via unprecedented collaboration in the multinational pharmaceutical industry and between governments. Multiple steps along the entire development path are evaluated, including:

  • the level of acceptable toxicity of the vaccine (its safety),
  • targeting vulnerable populations,
  • the need for vaccine efficacy breakthroughs,
  • the duration of vaccination protection,
  • special delivery systems (such as oral or nasal, rather than by injection),
  • dose regimen,
  • stability and storage characteristics,
  • emergency use authorization before formal licensing,
  • optimal manufacturing for scaling to billions of doses, and
  • dissemination of the licensed vaccine.

There have been several unique challenges with COVID‑19 vaccine development.Public health programs have been described as “[a] race to vaccinate individuals” with the early wave vaccines. Timelines for conducting clinical research – normally a sequential process requiring years – are being compressed into safety, efficacy, and dosing trials running simultaneously over months, potentially compromising safety assurance.

 For example, Chinese vaccine developers and the Chinese Center for Disease Control and Prevention began their efforts in January 2020, and by March they were pursuing numerous candidates on short timelines. The rapid development and urgency of producing a vaccine for the COVID‑19 pandemic were expected to increase the risks and failure rate of delivering a safe, effective vaccine. Additionally, research at universities is obstructed by physical distancing and the closing of laboratories.

Vaccines must progress through several phases of clinical trials to test for safety, immunogenicity, effectiveness, dose levels, and adverse effects of the candidate vaccine. Vaccine developers have to invest resources internationally to find enough participants for Phase II–III clinical trials when the virus has proved to be a “moving target” of changing transmission rates across and within countries, forcing companies to compete for trial participants.

Clinical trial organizers may also encounter people unwilling to be vaccinated due to vaccine hesitancy or disbelief in the science of the vaccine technology and its ability to prevent infection. As new vaccines are developed during the COVID‑19 pandemic, licensure of COVID‑19 vaccine candidates requires submission of a full dossier of information on development and manufacturing quality.

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