Dear Science,

Help me understand this new HIV-­antibody study. What does a "neutralizing antibody" mean? Are we really closer to an HIV vaccine? How wo uld this sort of antibody help? It's been a lot of years of so-called breakthroughs with no working vaccine. Is this really something or just a bunch of hype?

Wants to Be Vaccinated

Your frustration is understandable. In the decades since AIDS arrived, even to those working furiously in the lab, the promise of an HIV vaccine has been both close and far at the same time. This most recent development represents a real step forward; to understand how, we must understand how we create antibodies and how these antibodies ultimately protect us against infections.

Every antibody is basically the same structure: an unchanging stalk attached to two arms tailored to a specific invader. The arms grab on to the virus, bacteria, or parasite (or allergen if you're unfortunate). Defensive cells in the body responsible for gobbling up invaders recognize the common stalk of the antibody. Antibodies are at their most effective when they attach to some critical mechanism of the disease-­causing organism—a bit like booting the tire of a car, rather than simply putting a ticket on the window. Such antibodies are called neutralizing antibodies.

This brings up an interesting problem: To defend ourselves, we must be able to make antibodies tailored to any possible pathogen. Yet a vast number of potential pathogens exist—far too many to simply have one gene for each of them. Instead, our bodies generate antibodies by a combination of tightly controlled mutation and natural selection—basically evolution. Our B cells (responsible for making antibodies) start with a generic antibody-making gene and then mutate the hell out of the pathogen-recognizing arms. When an infection starts, the B cells each try their antibody out on the bug. Those with a good match are allowed to divide, grow up, and start pumping out their custom-mutated antibody. This process of mutation and selection takes a week or so to complete. (This is why it takes you about a week to really get over a cold.)

HIV mucks up this process by constantly changing its coating. In a new HIV infection, the B cell that wins the contest is almost always against a part of the viral coating that rapidly changes. By the end of the week, the virus is different. Only tiny portions of the viral coating—those responsible for getting the virus into human cells, for example—cannot change. Only antibodies against these rare portions can truly neutralize an HIV infection.

What these recent papers in the journal Science describe are a handful of antibodies that find their way right to these critical, unchangeable parts of the HIV virus. Now we know what kinds of antibodies a successful vaccine must produce. Hence, we're a bit closer to a successful vaccine with this knowledge.

Selectively Yours,

Science

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