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Updated: Jul 2, 2025
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Robust Immune Response and Protection against Lethal Pneumococcal Challenge with a Recombinant BCG-PspA-PdT
Monalisa Martins Trentini1, Dunia Rodriguez1, Alex Issamu Kanno1
1Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo 05503-900, Brazil.
Insights
A novel prime/boost vaccine strategy using recombinant BCG expressing PspA-PdT protected newborn mice against pneumococcal disease. This approach induced robust immune responses, offering 100% protection in neonates.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Pneumococcal diseases pose a significant global health threat, particularly to young children, with high mortality rates.
- Current pneumococcal vaccines have limitations, including serotype specificity and lack of protection in neonates, necessitating novel vaccine development.
Purpose of the Study:
- To evaluate a prime/boost vaccination strategy using recombinant BCG expressing PspA-PdT (rBCG PspA-PdT) followed by rPspA-PdT in neonatal mice.
- To assess the immunogenicity and protective efficacy of this strategy against lethal pneumococcal challenge.
Main Methods:
- Groups of neonatal C57/Bl6 mice were immunized with rBCG PspA-PdT (prime) and rPspA-PdT (boost) or controls (saline, antigen alone).
- Humoral and cellular immune responses, including antibody isotypes (IgG1, IgG2c), memory cell populations, and cytokine profiles (IFN-γ, IL-17, TNF-α, IL-10, IL-6), were analyzed.
- Mice were challenged with Streptococcus pneumoniae strain WU2 to determine survival rates.
Main Results:
- The rBCG PspA-PdT/rPspA-PdT prime/boost strategy induced an IgG1 to IgG2c isotype shift and increased specific memory T and B lymphocytes.
- Elevated levels of key cytokines (IFN-γ, IL-17, TNF-α, IL-10, IL-6) were observed in the prime/boost group.
- This strategy resulted in 100% protection against lethal pneumococcal challenge in neonates, whereas two doses of rPspA-PdT alone showed non-significant protection.
Conclusions:
- A prime/boost strategy combining rBCG PspA-PdT and rPspA-PdT is highly effective in protecting neonates against severe pneumococcal infections.
- This vaccination approach elicits strong antibody and cytokine-mediated immune responses crucial for neonatal protection against pneumococcal disease.
Abstract:
Pneumococcal diseases are an important public health problem, with high mortality rates in young children. Although conjugated pneumococcal vaccines offer high protection against invasive pneumococcal diseases, this is restricted to vaccine serotypes, leading to serotype replacement. Furthermore, the current vaccines do not protect neonates. Therefore, several protein-based pneumococcal vaccines have been studied over the last few decades. Our group established a recombinant BCG expressing rPspA-PdT as a prime/rPspA-PdT boost strategy, which protected adult mice against lethal intranasal pneumococcal challenge. Here, we immunized groups of neonate C57/Bl6 mice (6-10) (at 5 days) with rBCG PspA-PdT and a boost with rPspA-PdT (at 12 days). Controls were saline or each antigen alone. The prime/boost strategy promoted an IgG1 to IgG2c isotype shift compared to protein alone. Furthermore, there was an increase in specific memory cells (T and B lymphocytes) and higher cytokine production (IFN-γ, IL-17, TNF-α, IL-10, and IL-6). Immunization with rBCG PspA-PdT/rPspA-PdT showed 100% protection against pulmonary challenge with the WU2 pneumococcal strain; two doses of rPspA-PdT showed non-significant protection in the neonates. These results demonstrate that a prime/boost strategy using rBCG PspA-PdT/rPspA-PdT is effective in protecting neonates against lethal pneumococcal infection via the induction of strong antibody and cytokine responses.
