Vaccine against whooping cough: the power of first impressions

The current pertussis vaccine was universally adopted in the United States in 1996 to replace the original vaccine based on Bordetella pertussis killed because of a stronger safety profile. The new formulation has proven effective in preventing whooping cough during the vulnerable stages of life, but the type of pertussis vaccine used to prime the immune system leaves a lasting impression. In their latest study, researchers at the La Jolla Institute of Allergy and Immunology (LJI) report that people who were vaccinated with the new vaccine as part of their first round of vaccines have a lower response to the recall. 19659002] "We see a dramatic impression effect according to whether people have received the old or the new pertussis vaccine as part of their original immunizations for children," says Alessandro Sette, senior professor of the study, Dr. Biol. Sci., Head, Vaccine Discovery Division. "Even though the booster shots they received in middle and high school or at adult age contained the same vaccine, the immune system keeps a very vivid memory of what he saw during the first immunization. " Discovering the differences between the two vaccines is essential to understanding how best to prevent whooping cough and can also provide important lessons about the effectiveness of the vaccine in general, potentially applicable to other vaccines. Specifically, the study, to be published in the Journal of Clinical Investigation, found that the new vaccine did not generate a robust T-cell response, which provides long-term memory that allows the Immune system to react quickly if exposed to the pathogen. "Ideally, you should engage both arms with a protective response against the pathogens – the B cells that produce antibodies and the T cells that generate long-term memory," says Ricardo Antunes, Ph.D. postdoctoral researcher at the Sette laboratory. "But apparently, the new vaccine fails to generate an adequate T-cell response."

Traditionally, the ability to induce a high titer of antibodies was the measure against which vaccines were measured. The important role of T lymphocytes is increasingly appreciated and the key point of our study is to show that there are striking differences in T cell response to two different vaccines, "says Antunes

. Bordetella pertussis, the bacterium responsible for whooping cough, produces a toxin that causes uncontrollable and sometimes fatal coughing fits. Before a vaccine is available, whooping cough has killed thousands of people and has made hundreds of thousands of sufferers each year. With the introduction of the first vaccine, made from dead bacteria, cases have significantly decreased, but the unwanted side effects of the whole cell preparation have led the United States and many other countries to switch to formulas. acellular bacteria based on purified bacteria. proteins to induce immunity. Vaccination against the disease currently consists of a series of five injections given to young children aged 2, 4 and 6 months, between 15 and 18 months, and a fifth dose between 4 and 6 years and a final booster between 11 and 12 months. years. Pregnant women receive a single vaccine during the third trimester of pregnancy to protect newborns, the population most at risk for complications of pertussis. Despite booster shots, whooping cough cases have started to increase in recent years and more than 20,000 cases have been reported in the country in 2015.

The birth years of the most affected adolescents and young adults by the sudden increase of whooping cough coincide. With the move from malaria vaccine to aP vaccine, the question arose as to whether the new vaccine formulation offered less protection.

To find answers, the LJI team recruited 114 healthy adults who had been vaccinated with wP or aP at the start. infants and administered booster vaccinations with AP in middle and high school and at adult age and analyzed their immune response at regular intervals. Their results clearly showed that priming in the first months after birth with aP or wP vaccines induces different T-cell responses. Although both are initially able to generate protective immunity, the differences are changing over 15 years old.

In addition to subtle changes in B cell populations and cytokine secretion, T cells primed with PA gradually lose their ability to respond to booster vaccination. . "These cells stay there and do nothing while wP-primed T cells respond with a boost," says Antunes. Detailed transcriptomic analyzes revealed a decrease in the activity of genes associated with cell proliferation.

"Since we can see clear differences in the immune signatures induced by the two different vaccines in the days of a booster, this suggests that a potential route would be" Sette

L & # 39; study was funded in part by the Institute of Allergy and Immunology La Jolla and the National Institute of Allergy and Infectious Diseases (HHSN272200900044C, NIH U19 AI118626 and NIH S10OD016262.)

Reference: Ricardo da Silva Antunes, Mariana Babor, Chelsea Carpenter, Natalie Khalil, Mario Cortese, Alexander Mentzer J., Gregory Seumois, Christopher D. Petro, Lisa Purcell, Pandurangan Vijayanand, Shane Crotty, Bali Pulendran, Bjoern Peters and Alessandro Sette: Th1 / Th17-polarization persists following full-cell pertussis vaccination despite repeated acellular boosters Journal of Clinical Investigation, June 2018.

Source: La Jolla Institute of Allergy & D & # 3 9 Immunology