Reagents for Diphtheria Vaccine Development
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Pertussis (whooping cough) is an acute respiratory tract infection caused by Bordetella pertussis. A paroxysmal, spasmodic cough with a characteristic high-pitched "whoop" at the end of coughing episodes and weeks to months of illness duration are the disease's main clinical features from which its name is derived. In adolescents and adults, the disease is most commonly confined to a chronic cough. However, in infants (especially unimmunized and immunocompromised infants younger than six months) the disease can easily result in pneumonia, encephalopathy, asphyxia and death and is therefore a leading cause of infant death.
The course of pertussis is typically divided into three stages, but not all patients experience the classic progression through all three stages.
Table 1. Classic Stages of Pertussis in Adolescents and Adults. (Source: Kline JM, et al. 2021)
| Stage | Duration | Signs and symptoms |
| Catarrhal | 1 to 2 weeks | Highly contagious Insidious onset with gradual progression Malaise, rhinorrhea, dry cough, and lacrimation No or mild fever |
| Paroxysmal | 1 to 6 (sometimes up to 10) weeks | Apnea associated with paroxysms Chest and abdominal soreness Leukocytosis, lymphocytosis, and weight loss Paroxysmal coughing (periods of rapid succession coughing during one exhalation) Posttussive emesis, cyanosis, and exhaustion Scleral hemorrhage Whooping on inspiration after coughing |
| Convalescent | 2 to 4 weeks | Coughing lessens Susceptibility to respiratory infections |
The pertussis vaccines currently in use worldwide can be generally classified as being one of two types: whole-cell pertussis and acellular pertussis vaccines. These vaccines differ in several important characteristics, including safety, efficacy, and duration of protection. These differences have implications for current epidemiology of pertussis.
Whole-cell vaccine (wP)
Made from inactivated whole Bordetella pertussis cells, containing thousands of antigenic components.
Acellular vaccine (aP)
Made with purified major virulence factors of the pertussis bacterium, e.g., pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae (FIM), pertactin (PRN), etc. as antigenic determinants.
Table 2. Comparison of Whole-Cell and Acellular Pertussis Vaccines
| Whole-cell vaccine | Acellular vaccine | |
| Immune response | Th1/Th17–dominant | Th2/Th17–dominant |
| Mechanism of protection | Pathogen clearance, blockade of colonization and transmission | Prevention of overt disease, does not block colonization or transmission |
| Duration of immunity | >10 years (strong cellular memory) | 5–7 years (antibody-mediated, wanes quickly) |
| Herd immunity effect | Significant (reduces community transmission) | Limited or none (allows asymptomatic transmission) |
| Induction of mucosal immunity | Strong | Weak or none |
Multiple countries have reported Bordetella pertussis strains lacking the key acellular vaccine antigen—membrane-bound autotransporter PRN. Under aP vaccine pressure, B. pertussis readily loses PRN while retaining other antigens.
PRN is the only aP antigen tightly associated with the bacterial outer membrane. Binding of antibodies PRN creates a high-density, organized array on the surface capable of efficiently recruiting and activating complement component C1q, leading to complement cascade activation, membrane attack complex formation, and bacterial lysis and enhanced phagocytosis. In contrast, other aP antigens (PT and FHA) are secreted proteins, and fimbriae extend long distances away from the cell surface; binding of antibodies to these antigens primarily neutralizes toxins or distant structures, has no effective surface-directed complement activation or phagocytic killing, and does not block nasopharyngeal colonization.
Figure 1. Model for various roles of antibodies against antigens in acellular pertussis vaccine. (Source: Ma L, et al. 2021)
To simplify immunization schedules, improve compliance, and reduce healthcare costs, combining pertussis vaccine antigens with other childhood vaccine antigens into combination vaccines has become a global development trend.
Trivalent vaccine
Tetravalent and pentavalent vaccines
Hexavalent vaccine (DTaP-IPV-Hib-HepB)
Adds hepatitis B vaccine antigen to the pentavalent vaccine, including:
References
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