Understanding B Cell Hypermutation in the Quest for an HIV Vaccine


The two papers attached are a short review and an article.

The story is about how people develop HIV resistance through B cell hypermutation. It’s a little immunologically dense, but the basic (and highly simplified) point is this: HIV infects T cells by binding CD4 (a chemokine receptor on the T cell surface). The viral protein that binds CD4 is called gp120. Once HIV infects a person, it starts mutating gp120 like crazy so that it can avoid detection by B cells (each of the 4 gagillion B cells in your body encodes a different B cell receptor that, by chance, may bind with any pathogen that infects you). Here is where it gets interesting. In some (most?) people, there are a subset of B cells whose receptors can bind the original (not highly mutated) version of gp120. In a very small group of people, these B cells mutate at a rate that keeps pace with the gp120 mutations. Essentially, the HIV virus mutates gp120 into a new form, and the host B cell receptor mutates into a form that can bind the “new” gp120. This process is called hypermutation. Normally, some hypermutation occurs whenever a B cell recognizes an antigen to “optimize” the anitbody that the B cell ends up spitting out. However, in the vast majority of people, the B cell that recognizes the original gp120 can’t mutate fast enough to keep up with the virus and the person loses any semblance of HIV resistance.
Now the really cool part…
In a very lucky subset of people, the B cell hypermutation keeps pace with gp120 mutation for a long time. Eventually, the gp 120 “runs out” of mutation options. It gets to the point at which if it mutates any more, it will no longer bind CD4 and the virus will lose its ability to infect. So the HIV is trapped, and is cleared.
Scientists, like Michel Nussenzweig, are just starting to work out the specifics of this process in people who develop broadly neutralizing HIV antibodies. And some are trying to develop ways to force normal peoples’ B cells to undergo this HIV specific hypermutation. If they can manage to do that (that’s a big/ complicated if), the chance of developing an HIV vaccine is fairly high.
Review – Roadmaps to a Vaccine – Mouqet and Nussenzweig
Article – Co-evolution of a Broadly Neutralizing HIV-1 Antibody and Founder Virus – Nature – Liao et al.

Many Prices, Most Too High


Many Prices, Most Too High

Remember the “chargemasters” from Steven Brills fantastic article on healthcare costs in America (TIME magazine- Bitter Pill)?

Well the Centers for Medicare and Medicaid Services have compiled “hospital-specific charges for the more than 3,000 U.S. hospitals… for the top 100 most frequently billed discharges”

Not surprisingly, and in accordance with Steven Brill’s article, the data “show significant variation across the country and within communities in what hospitals charge for common inpatient services.”

It’s important to remember that Medicare payments for these services are not tied to the hospital charges. The CMS’ staggering bargaining power, derived from the millions of patients it serves, allows it to offer hospitals standardized “take-it-or-leave-it” rates for common procedures. Insurance companies also pay rates lower than those on the chargemasters because they too have significant bargaining power. In practice, only the uninsured and underinsured pay these or close to these rates.

Clearly, unified bargaining by healthcare consumers works to mitigate the radical knowledge and leverage imbalance enjoyed by health care providers.

I don’t know about you, but I haven’t seen a better illustration of the need for a single payer system in America.


Patenting Our DNA?

Can we patent life? In a new case soon to be heard by the Supreme Court, The Association for Molecular Pathology v. Myriad Genetics, INC., we will soon have an answer. Myriad will attempt to defend its claim to the rights of two genes – BRCA1 and BRCA2 – both of which are strongly associated with breast and ovarian cancers. The company claims that the “isolated molecules of deoxyribonucleic acid are particular molecular compositions designed based on the Myriad inventors’ identification and characterization of the structure of the BRCA genes, and separated from the other cellular content by the inventors based on those designs.” As per the current patent, anyone conducting experiments on the two BRCA genes without a license can be sued for infringement.

In a related case, Vernon Hugh Bowman v. Monsanto, a 75 year-old Indiana farmer will contest whether Monsanto’s seed patents extend beyond the first generation of products. Will human procreative rights be next? Future parents beware, PAT. NO. 9,023,865 (Human Baby), may be more costly than you ever imagined.

The Cost of Health Care

In a 24,000 word exposé appearing in Time Magazine last month, Steven Brill debunks the irrational, inhumane, and infuriating features of the American health care marketplace. Brill flips the conventional policy debate on its head, focusing not on who (or what) will be responsible for paying the bills but rather why the bills are so high to begin with. Along the way, we learn of the “$21,000 Heartburn Bill,” a $7 “Platinum” (quotations mine) alcohol pad, and the 9900% markup on generic Tylenol.


This is an important read – both for those of us entering health care as a career and those who have yet to set foot in a doctor’s office.

Eat Like a Mediterranean

In the first major, randomized, controlled clinical trial to test the effect of diet on cardiovascular disease risk, study leaders were able to end the trial prematurely because the benefits were so pronounced after just 5 years. Nearly 7,500 people participated in the trial, which showed a relative risk (stroke, heart attack, death from CV disease) reduction of 30% among those following a Mediterranean diet compared to those on a control diet.

The Mediterranean diet, as defined by the study protocol, consisted of mostly “grains, legumes, nuts, vegetables, and fruits; a relatively high-fat consumption, olive oil for culinary use and dressing of vegetables as the principal source of fat; moderate to high fish consumption; poultry and dairy products (usually as yogurt or cheese) consumed in moderate to small amounts; low consumption of red meats, processed meats, and meat products; moderate alcohol intake, usually in the form of red wine consumed with meals.”

Treating Severe Malnutrition in Malawi – The Power of Antibiotics

Researchers from Washington University in St. Louis have shown that the addition of antibiotics to ready-to-use therapeutic food (RUTF) can drastically reduce the mortality rate of severely malnourished Malawian children. In nearly 2,800 children, ages 6 months to 5 years, there was 44 percent drop in mortality with the use of cefdinir and a 36 percent drop with amoxicillin compared to those receiving RUTF alone. The results highlight the importance of treating both starvation and the resulting infections in this vulnerable population.


With these powerful data in hand, the question now becomes how to go about delivering these life-saving medications to those who need it most. The amoxicillin cost an average of $2.67 per child while the cefdinir cost $7.85. An efficient and robust mechanism for administering these medications is warranted. Cost, here, is not the issue.

Electronic Medical Records – Are They Worth It?


Electronic medical record (EMR) systems had been heralded as a means of reducing health care costs and improving quality. Unfortunately, emerging evidence suggests that these systems have failed to do so. Difficult to use software and a lack of integration between – and even within – health care organizations have led to mass confusion and, paradoxically, an increase in billing for provider services.

Personally, I am confident that EMRs have the potential to reduce health care costs and improve quality. However, until there exists an easy to use, fully-integrated national EMR database, this potential cannot be realized.

Thanks to Dr. Elpern for sending us this article.