Whooping cough vaccine: The power of first impressions

July 9, 2018, La Jolla Institute for Allergy and Immunology
Type of pertussis vaccine used to prime immune system permanently skews immune response. Credit: Dr. Ricardo Antunes, La Jolla Institute for Allergy and Immunology

The current whooping cough vaccine was universally adopted in the US in 1996 to replace the original vaccine based on killed Bordetella pertussis because of a stronger safety profile. The new formulation was found to be effective in preventing whooping cough during vulnerable stages in the lifespan but the kind of pertussis vaccine used to prime the immune system leaves a lasting impression. In their latest study, researchers at La Jolla Institute for Allergy and Immunology (LJI) report that individuals who had been inoculated with the newer vaccine as part of their initial series of shots, mount a weaker recall response when receiving booster shots later on.

"We see a dramatic imprinting effect depending on whether people received the old or the new as part of their original childhood immunizations," says the study's senior author LJI professor Alessandro Sette, Dr. Biol. Sci., head of the Division of Vaccine Discovery. "Even if the booster shots they received as middle and high schoolers or as adults contained the same vaccine the immune system still has a very striking recollection of what it saw during the first immunization."

Unraveling the differences between the two vaccines is key to understanding of how to better prevent and may also provide important lessons on in general, potentially applicable to other vaccines.

Specifically, the study, which is slated to be published in the Journal of Clinical Investigation, found that the new vaccine fell short of generating a robust T , which provides the long-term memory that allows the immune system to mount a rapid response if exposed to the pathogen. "Ideally, you should engage both arms of a protective response against pathogens—B cells that produce antibodies and T cells that generate long-term memory," says first author Ricardo Antunes, Ph.D., a postdoctoral researcher in the Sette lab. "But apparently the new vaccine fails to generate an adequate T cell response."

Traditionally the ability to induce a high antibody titer has been the yardstick against which vaccines have been measured. "Although B cells are a very important component of vaccine efficacy, the important role of T cells is being more and more appreciated and the key point of our study is to show that there are striking differences in the T cell response to the two different vaccines," says Antunes.

Bordetella pertussis, the bacteria that causes whooping cough, produces a toxin that causes uncontrollable, sometimes deadly coughing fits. Before a vaccine became available, whooping cough killed thousands of people and caused hundreds of thousands to become ill year after year. With the introduction of the first vaccine, which was crafted from dead bacteria, cases dramatically declined but unwanted side effects from the whole cell (wP) preparation led the U.S. and many other countries to switch to acellular (aP) formulas that relied on purified bacterial proteins to induce immunity.

Vaccination against the disease currently involves a series of five shots given to young children at 2, 4 and 6 months of age, somewhere between 15 and 18 months, and a fifth dose between 4 and 6 years old and a final booster between 11 and 12 years old. Pregnant women receive a single shot in the third trimester of pregnancy to protect newborns, the population at highest risk for pertussis complications. Despite the added booster shots, whooping cough cases in recent years began to increase, and by 2015 more than 20,000 cases were reported nationwide.

Since the birth years of the teenagers and young adults most affected by the sudden increase in pertussis cases coincided with the nationwide switch from the wP to the aP vaccine, the question arose whether the new formulation afforded less protection.

To look for answers, the LJI team recruited 114 healthy adults who had been originally either vaccinated with wP or aP in infancy and administered booster vaccinations with aP in middle and high school and as adults and analyzed their immune response at regular intervals. Their results clearly showed that priming in the first few months after birth with the aP or wP vaccines induces different T cell responses. Although both are initially capable of generating protective immunity, differences evolve over more than 15 years.

In addition to more subtle shifts in B cell populations and cytokine secretion, T cells originally primed with aP gradually lose the ability to respond to booster vaccination. "These cells just sit there and do nothing while T cells primed with wP respond with a pronounced boost," says Antunes. Detailed transcriptomics analyses revealed diminished activity of genes associated with cell proliferation.

"Since we can see clear differences in the immune signatures induced by the two different vaccines within days of a booster, this suggests that a potential path forward would be to test if new vaccines might be able to reproduce the more protective signature," says Sette.

Explore further: Tdap vaccine given during pregnancy reduces occurrence of infant pertussis

More information: Th1/Th17-polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters. Journal of Clinical Investigation, June 2018. DOI: 10.1172/JCI121309

Related Stories

Tdap vaccine given during pregnancy reduces occurrence of infant pertussis

June 14, 2018
A study published today in the American Journal of Preventive Medicine shows the effectiveness of the Tdap (tetanus, diphtheria, acellular pertussis) vaccine for infants whose mothers receive the vaccine during pregnancy. ...

Study finds effectiveness of routine Tdap booster wanes in adolescents

February 5, 2016
A new study from Kaiser Permanente's Vaccine Study Center found that the Tdap booster vaccine provides moderate protection against whooping cough during the first year after vaccination, but its effectiveness wanes to less ...

Protecting newborns from pertussis

August 24, 2017
Dear Mayo Clinic: I am four months pregnant and live in an area where there has been a pertussis outbreak. What's the best way to keep my newborn baby safe until he or she can get the vaccine?

Why is whooping cough on the rise?

March 19, 2018
Watching an infant suffer through a bout of whooping cough is agonizing. Blue face scrunched with effort, the baby strains to take a breath through a narrowed windpipe. She struggles, choking, for what seems like eons. Finally, ...

Whooping cough shot works, but many moms-to-be skip it: CDC

September 28, 2017
(HealthDay)—Tdap vaccination during pregnancy prevents whooping cough in about three-quarters of newborns—but only about half of mothers-to-be get the shot, a new U.S. study reveals.

Hybrid vaccination protocol could cut whooping cough cases by 95 percent

March 30, 2016
Whooping cough is making a major comeback in the United States right now, and public health officials are struggling with what to do about it. Now, two SFI researchers have a surprising proposal: go back to an old vaccine—one ...

Recommended for you

Drug targets for Ebola, Dengue, and Zika viruses found in lab study

December 13, 2018
No drugs are currently available to treat Ebola, Dengue, or Zika viruses, which infect millions of people every year and result in severe illness, birth defects, and even death. New research from the Gladstone Institutes ...

Faster test for Ebola shows promising results in field trials

December 13, 2018
A team of researchers with members from the U.S., Senegal and Guinea, in cooperation with Becton, Dickinson and Company (BD), has developed a faster test for the Ebola virus than those currently in use. In their paper published ...

Urbanisation and air travel leading to growing risk of pandemic

December 13, 2018
Increased arrivals by air and urbanisation are the two main factors leading to a growing vulnerability to pandemics in our cities, a University of Sydney research team has found.

Researchers discover new interactions between Ebola virus and human proteins

December 13, 2018
Several new connections have been discovered between the proteins of the Ebola virus and human host cells, a finding that provides insight on ways to prevent the deadly Ebola virus from reproducing and could lead to novel ...

Faecal transplants, 'robotic guts' and the fight against deadly gut bugs

December 13, 2018
A simple compound found in our gut could help to stop dangerous bacteria behind severe, and sometimes fatal, hospital infections.

Taking the virus out of a mosquito's bite

December 12, 2018
They approach with the telltale sign—a high-pitched whine. It's a warning that you are a mosquito's next meal. But that mosquito might carry a virus, and now the virus is in you. Now, with the help of state-of-the-art technology, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.