Combination of pneumococcal surface protein A (PspA) with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice
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Updated: Jun 12, 2026
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Maria Leonor S Oliveira1, Eliane N Miyaji, Daniela M Ferreira
1Centro de Biotecnologia, Instituto Butantan, São Paulo, São Paulo, Brazil. mloliveira@butantan.gov.br
Insights
Whole cell Bordetella pertussis vaccine (wP) acts as an adjuvant for Pneumococcal surface protein A (PspA) nasal vaccines, providing protection against Streptococcus pneumoniae. This combination shows promise for developing new infant vaccines.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Streptococcus pneumoniae causes severe respiratory infections globally, leading to significant child mortality in Latin America.
- Pneumococcal surface protein A (PspA) is a promising antigen for subunit vaccines due to its protective role in animal models.
- There is a need for cost-effective adjuvants to enhance the efficacy of PspA-based vaccines.
Purpose of the Study:
- To evaluate the adjuvant properties of whole cell Bordetella pertussis vaccine (wP) when combined with PspA for nasal immunization.
- To assess the protective efficacy of PspA-wP formulations against lethal Streptococcus pneumoniae challenge.
- To investigate the role of Bordetella pertussis lipopolysaccharide (LPS) and Toll-like receptor 4 (TLR4) in the adjuvant activity and protective mechanisms.
Main Methods:
- BALB/c mice were nasally immunized with PspA5 combined with wP or a low-LPS wP variant (wP(low)).
- Mice were subsequently challenged with a lethal dose of Streptococcus pneumoniae to assess protection.
- Immune responses, including systemic and mucosal antibody levels against PspA5 and cross-reactivity, were analyzed.
- C3H/HeJ mice (TLR4-deficient) were used to evaluate the role of TLR4 in adjuvant activity.
- Passive immunization experiments were conducted to determine the role of antibodies in protection.
Main Results:
- Nasal immunization with PspA5-wP and PspA5-wP(low) conferred protection against lethal pneumococcal challenge.
- Both vaccine formulations induced high levels of systemic and mucosal anti-PspA5 antibodies with similar profiles, suggesting LPS is not essential for wP's adjuvant effect.
- Protection was observed in TLR4-deficient mice, indicating that TLR4 responses are not required for the adjuvant activity or protective mechanisms.
- High anti-PspA5 antibody levels correlated with cross-reactivity against PspAs from different clades and conferred cross-protection.
- Passive immunization confirmed the crucial role of antibodies in protection.
Conclusions:
- Whole cell Bordetella pertussis vaccine (wP) effectively serves as a nasal adjuvant for PspA-based vaccines, inducing protective systemic and mucosal immunity.
- The adjuvant properties of wP are independent of Bordetella pertussis LPS and TLR4 activation.
- These findings support the development of novel, cost-effective pneumococcal vaccines, potentially as a combined DTP-PspA infant vaccine.
Abstract:
Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA) is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP) that is currently part of the DTP (diphtheria-tetanus-pertussis) vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wP(low)--a new generation vaccine that contains low levels of B. pertussis LPS--conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wP(low) vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTP(low) protected mice against challenge with two different pneumococcal strains, opening the possibility for the development of a combined infant vaccine composed of DTP and PspA.
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