Acknowledgements

which was detected after DTaP<sup>1</sup> (administered to children under 7 years of age) vaccination [69]. Maternal antibodies were also shown to interfere with the antibody response to the primary vaccination administered during infancy to children born to Tdap1 (administered to older children and adults)-vaccinated mothers [62, 70]. Interestingly, a mouse model showed that the vaccination of infant mice reduced the protective functions of maternally derived antibodies in vitro and in vivo [29]. A study that focused on vaccinations with Repevax, a five component aPV combined with tetanus, low-dose diphtheria, and inactivated polio vaccine (Sanofi Pasteur), detected a significant attenuation of pertussis antibodies in infants whose mothers were vaccinated with Repevax during pregnancy [71]. Together with the diminished protection afforded by aPVs, recent findings suggest that the efficacy of current vaccines should be maximized by prenatal vaccination followed by boosting. It is important to continue studies to determine the functionality of maternal antibodies resulting from vaccinations during pregnancy and infant antibodies generated from subsequent vaccinations to better understand the potential for cross interference to design alternative vaccination strategies.

It is irrefutable that the worldwide incidence of severe pertussis cases is rising. Nearly 90% of all instances of deaths caused by pertussis occur in infants younger than 4 months of age and are caused by fatal pertussis pneumonia due to PTx activity [72], which highlights the need to inhibit PTx during an acute infection. Over the past few years, the scientific community has responded by initiating studies focused on a better understanding of virulence factors, like PTx, transmission dynamics, and host immune reactions, which can provide a foundation for the generation of a new vaccine but can also guide improvements in the use of current vaccines. It is clear that a control of pertussis requires a durable protection against disease and disruption of transmission. The two types of vaccines available, wPV and aPV, are effective in preventing the disease, but the immunity developed by each wane over time, even more rapidly with aPV, which should encourage countries in which wPV is still in use, not to switch to aPV. Further, transmission from vaccinated individuals is possible since B. pertussis can still colonize their respiratory tracts. Improvements to both types are in development, but it will be several years before their widespread use. In the interim, expansions in the use of the current vaccines have been proposed. Cocoon vaccination programs, which are controversial in their effectiveness, rely on generating herd immunity to protect young infants by vaccinating individuals with close contact. In contrast, immunization with aPV during pregnancy can reduce the incidence of severe and deadly pertussis in neonates. However, there are concerns that the antibodies raised from the maternal immunization can interfere with the immune response in the child to their primary vaccination. All approaches under development would benefit from

DTaP, Tdap, and Td are all similar vaccines, given for the same diseases at different times of life. Depending on the age, certain amounts of vaccine components are administered. Typing uppercase and lowercase letters denotes the component of the vaccine and the quantities in it. Uppercase letters in abbreviations denote undiluted doses of diphtheria (D), tetanus (T), and pertussis (P) toxoids. The lowercase letters d and p denote reduced doses of diphtheria and pertussis toxoids used

in formulations for adolescents and adults. The letter a in the DTaP and Tdap vaccines means acellular.

5. Conclusion

54 Pertussis - Disease, Control and Challenges

1

SGS received support from the Brazilian Council for Scientific Research (CNPq-no 467.488.2014- 2), Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ no E-26 110.198-13), and Higher Education Coordination for the Improvement (CAPES-no 2919-2010).
