The good old days

Ancient Bacterial DNA Could Thwart a Devastating Disease

The unique bacterial DNA of CpG oligonucleotides will reinforce the hepatitis B vaccine and could drop liver cancer rates.

Hepatitis B virus infects around 20,000 people per year in the United States, according to the CDC. Typically, the virus causes severe inflammation of the liver. Symptoms include fatigue, muscle aches, jaundice, abdominal pain, fever, discolored urine, weight loss, and an inability to tolerate fatty foods.

Normally, the virus comes and goes—but sometimes the virus causes long-term liver damage (cirrhosis) or liver cancer. In fact, hepatitis B virus is the most common cause of liver cancer in the world.

Two hepatitis B virus vaccines are currently on the market. Earlier this month, however, the Food and Drug Administration licensed another hepatitis B vaccine. This new vaccine employs a unique strategy: fighting the hepatitis B virus with … bacterial DNA.

Here’s how it works. All of our cells contain DNA, consisting of various combinations of nucleotides called cytosine, guanine, adenine, and thymine. DNA provides a blueprint that instructs cells on how to reproduce themselves.

Bacteria also contain DNA. Bacterial DNA, however, has certain patterns of nucleotides that aren’t found in human DNA. From the moment that we crawled out of the ocean onto land, we have been able to recognize these unique bacterial DNA patterns—a crude and early part of our immune system. There’s a reason for this primitive form of immunity: Once microbes breach the surface of our skin or intestines, where they live in large numbers, they can kill us. We need a defense system that is capable of recognizing these unique bacterial-specific molecular patterns and responding to them—immediately.

Which brings us back to the new hepatitis B vaccine. It’s identical to the two existing hepatitis B vaccines—which have been available since the 1990s—in that it contains 20 micrograms of a protein that is located on the surface of the virus. But unlike these other hepatitis B vaccines, the new vaccine also contains 3 milligrams of repeated linkages of cytosine and guanine—a molecular pattern unique to bacterial DNA called CpG oligonucleotides.

It’s the first time this immune-boosting product has been used in a vaccine. (The “p” just stands for the phosphodiester linkage that binds the cytosine and guanine.)

The FDA licensed this novel hepatitis B vaccine for people older than 18 years of age in certain high-risk groups like household contacts of someone who is infected, injection drug users, healthcare workers, or people with HIV, diabetes, or chronic lung or kidney diseases.

Although the existing hepatitis B vaccines have been lifesavers (virtually eliminating the disease in children), some problems have remained, especially for adults. About 5 percent of adults don’t respond to the vaccine. No matter how many doses are given, they are simply unable to make an adequate immune response. Second: some groups, including those most likely to benefit, don’t always develop an effective response. This is where the CpG oligonucleotides come in.

The CpG-containing hepatitis B vaccine has now been tested in about 14,000 adults. To figure out whether this novel vaccine strategy worked, researchers tested the quantity of hepatitis B virus-specific antibodies in serum (seroprotection). Two doses of the new hepatitis B vaccine were compared to three doses of one of the other hepatitis B vaccines. Seven months after the last dose, 95 percent of those who had received the vaccine containing the CpG motif developed protective antibodies as compared with 81.2 percent in the comparator group. The CpG vaccine also induced protective immunity more quickly and offered greater seroprotection in patients with type-2 diabetes (90 percent vs. 65.1 percent), people who were obese (94.7 percent vs. 75.4 percent), and people who smoked (95.3 percent vs. 78.8 percent).

Furthermore, the CpG-containing hepatitis B vaccine worked better in all age groups, including those who were 18 to 29 years old (100 percent vs. 93.9 percent), 30 to 39 years old (98.9 percent vs. 92 percent), 40 to 49 years old (97.2 percent vs. 84.2 percent), 50 to 59 years old (95.2 percent vs. 79.7 percent), and 60 to 70 years old (91.6 percent vs. 72.6 percent).

Notably, the two hepatitis B vaccines tested were indistinguishable with regards to mild or severe reactions—with the exception of one weird observation. Using small numbers derived from the large database of 14,000 vaccine recipients, the new vaccine was found to cause a statistically significant increase in heart attacks, along with a statistically significant decrease in prostate cancer. Because both of these outcomes are biologically implausible, both can be viewed skeptically. The issue of heart attacks, however, will be followed up in post-licensure studies.

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Ironically, the best way to address the problems with the hepatitis B vaccine—as well as with any strategy necessitating the induction of long-lasting, specific immunity—might be to solicit the help of a part of our immune system that is designed to respond to something entirely different.