Acellular Pertussis Vaccine

The acellular pertussis vaccine (aP) is a modern immunisation developed to protect against Bordetella pertussis, the bacterium responsible for whooping cough — a highly contagious respiratory infection. It represents an important advancement in vaccine technology, replacing the earlier whole-cell pertussis vaccine (wP) in many countries due to its improved safety profile and reduced side effects. The acellular vaccine forms part of the combined diphtheria–tetanus–pertussis (DTP) immunisation schedule used globally.

Background and Development

Whooping cough, or pertussis, has been a major cause of infant morbidity and mortality worldwide. Before the introduction of vaccination in the mid-20th century, pertussis caused frequent epidemics, particularly affecting infants under one year of age. The whole-cell pertussis vaccine (wP), introduced in the 1940s, significantly reduced disease incidence but was associated with adverse reactions such as fever, swelling, and irritability. Although serious complications were rare, public concern over safety in the 1970s and 1980s prompted research into safer alternatives.
The acellular pertussis vaccine was developed in Japan in the early 1980s and later adopted internationally. It contains purified components (antigens) of B. pertussis rather than the entire inactivated bacterial cell, which substantially decreases reactogenicity while maintaining protective efficacy. These antigens stimulate an immune response specific to the pathogen’s key virulence factors.

Composition and Antigenic Components

Unlike the whole-cell version, which contains hundreds of bacterial proteins, the acellular vaccine is composed of highly purified antigens that are essential for inducing immunity. The specific composition varies among manufacturers, but most acellular pertussis vaccines include some or all of the following components:

• Pertussis toxin (PT): The major virulence factor; detoxified for vaccine use to induce neutralising antibodies.
• Filamentous haemagglutinin (FHA): A surface protein aiding bacterial attachment to respiratory epithelium.
• Pertactin (PRN): Another adhesion protein that enhances the immune response.
• Fimbriae (types 2 and 3): Surface structures contributing to bacterial adherence.

Vaccines containing three or more of these antigens are typically referred to as multicomponent acellular pertussis vaccines (DTaP). The “a” denotes acellular composition, while “DT” represents diphtheria and tetanus toxoids, which are administered together as part of routine immunisation schedules.

Mechanism of Action

The acellular pertussis vaccine works by inducing humoral and cellular immune responses against specific bacterial antigens. Following vaccination, the immune system produces antibodies that neutralise pertussis toxin and prevent bacterial attachment to the respiratory tract. Additionally, memory B and T cells are formed, ensuring rapid immune recognition upon subsequent exposure to the pathogen.
In contrast to the whole-cell vaccine, which elicits a broader but more reactogenic immune response, the acellular vaccine promotes a more targeted and less inflammatory reaction. However, it has been observed that the immunity conferred by the acellular vaccine wanes faster, leading to renewed research into booster strategies and vaccine reformulation.

Administration and Immunisation Schedule

The acellular pertussis vaccine is typically administered in combination with diphtheria and tetanus toxoids as DTaP for children and Tdap (a lower-dose formulation) for adolescents and adults. The standard immunisation schedule recommended by the World Health Organization (WHO) and national health authorities includes:

• Primary series: Three doses at 2, 4, and 6 months of age.
• Booster doses: At 15–18 months and again between 4–6 years.
• Adolescent and adult boosters: Every 10 years, or during pregnancy to protect newborns through maternal antibodies.

Vaccination of pregnant women during the third trimester is a key public health strategy for preventing pertussis in newborns, who are too young to receive the primary doses.

Advantages and Safety Profile

The introduction of the acellular vaccine markedly improved the safety and tolerability of pertussis immunisation programmes. Compared with the whole-cell version, it causes fewer systemic reactions and local adverse events. Common mild side effects include redness or tenderness at the injection site, low-grade fever, or mild irritability, which typically resolve within 24–48 hours.
The advantages of the acellular vaccine include:

• Reduced reactogenicity and improved public acceptance.
• Consistent antigenic composition, ensuring predictable immune responses.
• Compatibility with combination vaccines, simplifying immunisation schedules.
• Lower incidence of severe adverse events such as febrile seizures or hypotonic-hyporesponsive episodes.

These benefits have contributed to widespread adoption in high-income countries and to maintaining high vaccination coverage rates.

Limitations and Waning Immunity

Despite its safety advantages, the acellular pertussis vaccine presents challenges related to duration of protection. Studies have demonstrated that immunity following aP vaccination wanes significantly within 4–6 years, in contrast to the longer-lasting immunity provided by natural infection or the whole-cell vaccine. This waning immunity has been linked to resurgence of pertussis outbreaks in several countries, even in populations with high vaccination coverage.
Furthermore, molecular studies have identified pertactin-deficient strains of B. pertussis emerging in response to vaccine-driven selection pressure. These strains can partially evade immunity generated by acellular vaccines, highlighting the ongoing evolutionary dynamics between pathogen and host immunity.

Comparison with Whole-Cell Vaccine

This comparison illustrates the trade-off between reactogenicity and durability of protection. While the acellular vaccine remains the standard in many regions, some global health authorities advocate continued use of whole-cell formulations where feasible, especially in early childhood programmes.

Research and Future Directions

Current research aims to enhance the long-term efficacy of acellular pertussis vaccines through improved antigen design and novel adjuvant systems. Experimental approaches include:

• Adjuvant optimisation to stimulate stronger T-cell responses.
• Live attenuated nasal vaccines that mimic natural infection to induce mucosal immunity.
• Hybrid formulations combining acellular components with outer-membrane vesicles to broaden immune coverage.

Additionally, surveillance of circulating B. pertussis strains remains essential to monitor antigenic changes and guide vaccine updates.