Contributed by Guest Blogger: A. Lee ’14
HIV is particularly virulent due to its specific attack of host immune cells and disruption of their normal function. The human body needs helper T-lymphocytes (HTL), which coordinate and activate other immune cells, and cytotoxic T-lymphocytes (CTL), which attack infected cells, to work cooperatively to defeat illness. HIV attacks HTL and through its high sequence mutation rate evades the body’s attempts to identify a parts of it for counterattack, called epitopes; these constant, minute changes in the virus also makes vaccine development difficult. However, recent technological advances have allowed immunologists to circumvent this problem through study of HIV’s amino acid sequence, or its structural makeup.
Researchers have identified key epitopes of major HIV subtypes, recognizable by HTL and CTL, and combined them into two vaccines, a synthetic protein structure to activate HTL (called EP-1043) and a plasmid (DNA segment, EP HIV-1090) to activate CTL. EP-1043 was created by cutting the DNA sequence of the 18 epitopes into overlapping sequences, fusing that with insect and viral sequences to ensure viability in a bacterium, and using this sequence in a non-deadly virus to force a bacteria to create the protein. The EP-1090 DNA sequence was created using a similar process of combining epitopes into overlapping sequences and replicating them using a process called PCR (no similar process exists for replicating proteins). Importantly, EP-1043’s protein epitopes are joined by weak bonds, meant to break and spread the epitopes through the body. Because the protein aggregates (becomes useless) at blood pH, it is packaged in aluminum hydroxide (Alhydrogel) and aluminum phosphate gels, which dissolve later.
Effectiveness of the virus was measured 39-42 days after infection by measuring cytokine (cytokines are secretions of infected cells causing immune reaction) and by measuring reproduction of splenocytes (spleen immune cells). Though EP-1090 was ineffective, EP-1043 was significantly effective in causing immune. Despite the low toxicology of the vaccine, and the fact that a true vaccine for HIV would require CTL and HTL epitope response from singular cells, this is an important step towards combating HIV.
One wonders, then, what more complex methods can be used to amalgamate epitopes for vaccines, and what method immunologists will use to create true HIV vaccines, if at all possible. This method can be used for other, less complex viruses, but does this relatively non-specific, general epitope flood lessen the necessary specific response? Can the body handle such a large, sudden appearance of viral material?
I was fascinated by your description of how the constant mutations of epitopes almost single-handedly deter the body from being able to fight HIV. Having said that, I am hopeful about the development of an HIV vaccine that targets the underlying mechanism of the virus that allows it to escape immune system or medical attack. The question that you conclude on is valid – there is already much controversy over vaccine side-effects and whether or not every human body can handle them. Would it be able to handle the vaccine you describe? If not, what adjustment would need to be made to the mechanics of the vaccine? Only time will tell.