Who is immune to whooping cough

However, potent immune responses to B. When the cationic polysaccharide chitosan was combined with FHA and genetically detoxified PTx and administered intranasally, high serum IgG, and sIgA levels in lung lavages and nasal washes were observed to both antigens and were considerably higher than when the two antigens were given without chitosan Other nasal adjuvants are onjisaponins from the roots of Polygala tenuifolia. When onjisaponins were given nasally together with a pertussis vaccine, a significant increase in serum IgG, and nasal IgA levels to B.

However, the effect of these adjuvant formulations on protection was not examined in any of the two studies. CpG-containing oligodeoxynucleotides have also been shown to enhance systemic and local antibody responses to PTx, FHA, and pertactin when administered nasally and increased the protection against B.

More recently, bacterium-like particles BLP based on the food-grade bacterium Lactococcus lactis have been explored for intranasal vaccination These BLP are generated by the treatment of L.

When mixed with an acellular pertussis vaccine and administered intranasally, these particles strongly increased the serum IgG titers to the B. This was associated with a significant level of protection compared to mice that were intranasally vaccinated with the acellular pertussis vaccine in the absence of BLP. Outer membrane vesicles OMV are yet another promising approach for respiratory immunization. Ten years ago, Roberts et al. More recently, aerosol vaccination with B. Aerosol vaccination with the OMVs led to pulmonary anti- B.

Spray dried OMV with improved stability especially at high temperatures delivered twice by aerosol have also been shown to provide protection against B. Importantly, the spray dried formulation was more protective in the nose than the same OMV in a liquid formulation. Although some of these novel avenues show promise as mucosal vaccine candidates against pertussis disease and infection, none of them have yet entered clinical evaluation. So far, the most effective way to induce protective immunity against B.

Furthermore, immunity induced by natural infection is longer lasting than that induced by immunization These observations have led to the concept of live attenuated pertussis vaccines. The first live attenuated vaccine candidate was an aroA mutant of B. This strain did not persist in the lung and induced protection against challenge after repeated intranasal administrations.

A more recent aroQ mutant of B. A different strategy to engineer a live attenuated pertussis vaccine was based on the genetic elimination or inactivation of PTx, tracheal cytotoxin, and dermonecrotic toxin, which led to the vaccine candidate BPZE1. This vaccine candidate is highly attenuated, even in immune-compromised hosts, yet very immunogenic, and protective in mice after a single intranasal administration [for review see 79 ].

Recently it was also shown to be immunogenic in baboons and to elicit high levels of IgG and IgA against PTx, FHA, and pertactin and to protect these baboons from severe pertussis induced by challenge with a very high dose of a highly virulent B.

Furthermore, upon challenge with this highly virulent isolate it reduced the overall bacterial burden by BPZE1 is the most advanced novel pertussis vaccine candidate and has successfully completed phase I trials, where it was found to be safe in young human adults, able to transiently colonize the human nasopharynx, and to induce antibodies to PTx, FHA, pertactin and fimbriae after a single nasal administration This vaccine candidate is currently entering a clinical phase II trial.

Human monocyte-derived dendritic cells in vitro stimulated with BPZE1 were shown to polarize T cells toward a Th17 response Moreover, protection against B. The important role of IL in the protection against nasal colonization by virulent B.

Yet, routine vaccination is done parenterally, inducing circulating antibodies, and systemic cell-mediated immunity. Local mucosal immunity is not induced by the current vaccination regimens, which is likely the main reason why pertussis vaccination fails to control B.

The fact that in many countries, in which high coverage with acelullar vaccines containing pertactin is achieved, pertactin-deficient B. However, this is not sufficient to effectively control B.

It is most likely that local immunity is required for effective protection against infection by B. Potent local antibody and T-cell responses are indeed induced upon natural infection in humans and experimental infection in mice and non-human primates. Since infection induces sterilizing immunity, these responses are likely to play a critical role in infection control. Several attempts have been made in both humans and animal models to induce local immunity by vaccination via the oral or nasal route.

However, none of them have reached the stage of mass vaccination regimens. With a deeper understanding on protective local immunity, as it has emerged over the years, mucosal, especially nasal vaccination has recently attracted interest again, especially by using novel approaches, such as nasal delivery of live attenuated B. One such candidate, BPZE1, is currently in clinical development and shows promise for providing durable local immunity and improved control of pertussis.

It will of course be important to know whether nasal vaccines such as BPZE1 will protect against infection by the various B. Furthermore, the effect of maternal antibodies transmitted to the offspring on immunity induced by mucosal vaccines is not yet known. This is of particular importance, as maternal immunization against pertussis is now recommended in several countries, based on the high effectiveness of this strategy to protect infants against severe pertussis in the first months of life LS prepared the first draft of the paper and critically revised the final draft.

CL prepared the final draft of the paper. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

National Center for Biotechnology Information , U. Journal List Front Immunol v. Front Immunol. Published online Jan Author information Article notes Copyright and License information Disclaimer.

Lille, Lille, France. Reviewed by: Daniela F. This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology. Received Jul 31; Accepted Dec The use, distribution or reproduction in other forums is permitted, provided the original author s and the copyright owner s are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these terms. This article has been cited by other articles in PMC. Abstract Pertussis or whooping cough, mainly caused by Bordetella pertussis , is a severe respiratory disease that can affect all age groups but is most severe and can be life-threatening in young children.

Keywords: pertussis, secretory IgA, tissue-resident memory T cells, mucosal vaccine, live attenuated vaccine. Introduction Whooping cough, also referred to as pertussis, is a severe respiratory disease that can be life threatening in newborns and non-vaccinated young children.

Mucosal Immune Responses Induced by B. Pertussis Infection B. Open in a separate window. Figure 1. Concluding Remarks B. Author Contributions LS prepared the first draft of the paper and critically revised the final draft. References 1. Clinical practice. Pertussis—not just for kids. N Engl J Med. Mattoo S, Cherry JD. Molecular pathogenesis, epidemiology, and clinical manifestations of respiratory infections due to Bordetella pertussis and other Bordetella subspecies.

Clin Microbiol Rev. Clinical characteristics of illness caused by Bordetella parapertussis compared with illness caused by Bordetella pertussis. Pediatr Infect Dis J. Recovery of Bordetella holmesii from patients with pertussis-like symptoms: use of pulsed-field gel electrophoresis to characterize circulating strains.

J Clin Microbiol. An update of the global burden of pertussis in children younger than 5 years: a modelling study. Lancet Infect Dis. Global routine vaccination coverage, Black S. Epidemiology of pertussis. The researchers constructed two different models based on assumptions of the effects of pertussis exposure on a person whose immunity has lapsed and that person's relative contribution to transmission. Then they compared the models' predictions to whooping cough incidence data from England and Wales from both the pre-vaccine era and the vaccine era In particular, Rohani and Wearing looked for matches in two key measures: the number of years between big outbreaks and the frequency of "extinctions"periods of time when no whooping cough cases were reported in the population.

The analysis revealed that, on average, whooping cough immunity lasts at least 30 years and perhaps as long as 70 years after natural infection. In addition, repeat infections appear to contribute relatively little to the transmission cycle, the researchers found. And when people whose immunity has waned are re-exposed to whooping cough, they rarely become infected. In fact, their immunity to the disease may be boosted by re-exposure, the study suggests. If that person's immune system doesn't recognise the whooping cough bacteria, it can't start to fight the infection.

Once the whooping cough bacteria are breathed in, they stick to cells in the nose and throat and the bacteria start to reproduce rapidly. As the bacteria reproduce, they produce toxins that paralyse cells in the windpipe and lungs that clear the airways of mucus and debris.

Another bacterial toxin paralyses some of the body's immune cells and prevents them from attacking the bacteria. Whooping cough bacteria can also multiply inside the lung tissue and cause pneumonia it can also lead to other pneumonias with different bacteria and viruses. This also stops oxygen in the air from getting into the blood. With time, the body's immune system develops antibodies which are specialised immune proteins that recognise that whooping cough bacteria are foreign.

The antibodies stick to the bacteria and help the body's immune cells to respond to fight the infection. Initially, there are so many live bacteria in the throat that each cough can spread bacteria to others.

With time, the numbers of bacteria decrease and by 3 weeks, the numbers of live bacteria have normally been reduced so that the person is no longer able to easily pass the infection on to others, although the cough can linger for a number of weeks, until the airways recover. Specific antibiotic drugs are sometimes prescribed to help kill off the whooping cough bacteria that are reproducing in the respiratory tract early in the infection.

The result is that the numbers of bacteria fall more quickly. After 5 days of therapy, the numbers of bacteria are low and the person can no longer easily spread the infection to others. In older adolescents, adults and older people, pertussis often goes unrecognised and is under reported. Up to a third of adolescents and young adults with a persistent cough have evidence of recent pertussis infection.

Pertussis is highly contagious and is spread by coughing and sneezing. School children and adolescents tend to be infected by another student or friend. Many babies catch it from their older siblings or parents, often before they are old enough to be fully vaccinated.

Immunity wanes over time which means all adults are a potential source of infection for babies. A person with whooping cough is likely to be infectious from the week before they start coughing to three weeks after the cough begins.

About 5 — 10 days but sometimes up to 3 weeks after catching whooping cough, the early symptoms start, including a runny nose, sneezing, slight fever and a mild irritating cough which lasts 1 to 2 weeks. This is the most infectious period. Babies in this phase can get apnoea stop of breathing attacks. Infants and adults generally do not have the characteristic 'whoop'. Infants and young children often appear very unwell, and may turn blue and vomit with coughing bouts.

The recovery stage may last for months. Although the cough eventually disappears after several weeks, coughing fits may recur whenever the patient suffers any later respiratory infection. There is no treatment for whooping cough. Antibiotics, such as erythromycin, can be prescribed during the early stages to reduce spread of the disease.

They may reduce symptoms if given early enough. Those most at risk of serious disease are infants under 12 months of age. Infants who do not receive on-time doses of pertussis-containing vaccine at the scheduled times of 6 weeks, 3 months, and 5 months are five times more likely to be hospitalised with pertussis than those babies who are vaccinated on time.

Around half the babies who catch pertussis before the age of 12 months require hospitalisation and 1 or 2 in of those hospitalised die from pertussis infection. Severe coughing can temporarily stop the oxygen supply to the brain hypoxia.