For the first time, researchers at the Duke Human Vaccine Institute have successfully induced broadly neutralising antibodies (bNAbs) against HIV (human immunodeficiency virus) through vaccination.
- These studies introduce two nanoparticle-based vaccine candidates, N332-GT5 and eOD-GT8, designed to elicit broadly neutralizing antibodies (bNAbs) against HIV.
Human Immunodeficiency Virus (HIV)
HIV, a retrovirus, attacks the body’s immune system. If untreated, HIV can progress to AIDS (acquired immunodeficiency syndrome).
- Transmission: HIV primarily spreads through the exchange of certain bodily fluids such as blood, semen, vaginal fluids, and breast milk. Impact on the Immune System:
- HIV targets specific white blood cells (WBCs) and T-helper (CD4) cells crucial for the body’s immune response against infections and diseases.
- Symptoms: Most individuals experience flu-like symptoms within 2 to 4 weeks of infection, which may persist for days to weeks.
- Diagnosis: ELISA (Enzyme-Linked Immunosorbent Assay) Test: Detects and measures antibodies in the blood.
- Treatment: Antiretroviral Therapy Stem Cell Transplantation
- Prevention strategies include practicing safe sex, undergoing HIV testing and counseling, voluntary medical male circumcision, among other measures.
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Background of HIV Vaccines
- Historical Context: More than four decades after the first reported cases of AIDS, the scientific community remains steadfast in its pursuit of an effective HIV vaccine.
- First Reported Case: In 1981, Dr. Michael Gottlieb’s groundbreaking paper reported the first cases of acquired immunodeficiency syndrome (AIDS), initiating a global health crisis.
- Unlike many infectious diseases that have been controlled through vaccination, HIV remains a formidable challenge.
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Challenges in HIV Vaccine Development
- Challenge of HIV Variants: To illustrate, HIV can have more variants circulating within a single patient at any given time than the total number of strains challenging the development of an effective vaccine.
- HIV’s Immune Evasion: HIV evolves rapidly, outpacing the immune system’s ability to produce effective antibodies. This fast mutation rate renders traditional vaccination strategies ineffective.
Mechanisms of Immune Response
- Function of B-Cells: B-cells generate antibodies that target specific viral proteins. Upon encountering a matching protein fragment, B-cells refine their antibodies to effectively bind to the virus and neutralize it.
- Broadly Neutralizing Antibodies (bNAbs): Broadly neutralizing antibodies (bNAbs) can neutralize multiple variants of a virus, such as HIV, by targeting conserved regions on viral proteins crucial for infection.
- This makes them promising candidates for vaccine development and therapy against highly mutable viruses.
Advances in Vaccine Research
- Germline Targeting Approach: The germline targeting strategy includes three steps: identifying and activating B-cells capable of maturing into producers of broadly neutralizing antibodies (bNAbs), enhancing these cells to produce more potent bNAbs, and refining the antibodies to neutralize a wide range of HIV strains.
- N332-GT5: The N332-GT5 vaccine candidate targets the N332 glycan site on the surface of the HIV virus.
- It activates B-cells capable of producing broadly neutralizing antibodies (bNAbs) against this site, aiming to induce an immune response that protects against a diverse array of HIV strains.
- eOD-GT8 vaccine: The eOD-GT8 vaccine candidate targets the eOD protein region of the HIV virus. Utilizing nanoparticles as carriers, eOD-GT8 seeks to boost the immune system’s capacity to detect and neutralize HIV, thereby promoting the production of broadly neutralizing antibodies (bNAbs).
- mRNA Vaccines: The mRNA-based approach is praised for its potential because of its ease of development and production. Antibodies produced in response to these vaccines exhibited binding patterns comparable to well-known bNAbs.
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mRNA Vaccines
Messenger RNA (mRNA) is a single-stranded RNA molecule essential for protein synthesis. It is synthesized from a DNA template during transcription.
- Functions: mRNA functions by transporting genetic information from the DNA in the nucleus of a cell to its cytoplasmic environment, where ribosomes translate the mRNA sequence into amino acids, thereby assembling proteins.
- Thus, mRNA serves as a vital intermediary that enables cellular machinery to interpret and utilize genetic instructions encoded in DNA.
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June 14, 2024