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Published on: May 19, 2020
A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi
Ying-Jie Lu1, Fan Zhang, Sabina Sayeed
1Division of Infectious Diseases, Children's Hospital Boston, and Harvard Medical School, Boston, MA 02115, United States.
Insights
A new bivalent vaccine combining pneumococcal and typhoid fever antigens shows promise for children. This fusion conjugate vaccine generated stronger immune responses and protection against both diseases in mice.
Area of Science:
- Vaccinology
- Immunology
- Pediatric Infectious Diseases
Background:
- Pneumococcal and Salmonella typhi infections are significant childhood diseases in developing nations.
- Current vaccines for young children (<2 years) against typhoid fever are ineffective, and pneumococcal vaccines have limitations like cost and serotype coverage.
- Previous research demonstrated a fusion conjugate vaccine's efficacy against pneumococcal disease in mice.
Purpose of the Study:
- To develop a bivalent conjugate vaccine targeting both Streptococcus pneumoniae (pneumococcus) and Salmonella typhi (typhoid fever).
- To evaluate the immunogenicity and protective efficacy of this novel bivalent vaccine in a mouse model.
Main Methods:
- Two conserved pneumococcal antigens (SP1572, SP2070) were fused to a pneumolysoid (PdT).
- SP1572-PdT was conjugated to Vi polysaccharide, and SP2070-PdT to pneumococcal cell wall polysaccharide (CWPS).
- Mice were immunized with the bivalent conjugate and challenged with pneumococcus and S. typhi to assess protection and antibody responses.
Main Results:
- The bivalent conjugate vaccine protected mice against pneumococcal colonization and sepsis.
- Mice immunized with the bivalent conjugate produced 40-fold higher anti-Vi antibody concentrations compared to those receiving antigen mixtures.
- Plasma from immunized mice demonstrated enhanced in vitro killing of Vi-bearing Salmonellae.
Conclusions:
- The developed bivalent fusion conjugate vaccine is immunogenic and protective against pneumococcal and S. typhi challenges in mice.
- This approach offers a potential strategy for a combined vaccine to prevent pneumococcal disease and typhoid fever in young children.
- Further evaluation of this bivalent immunogen is warranted for clinical development.
Abstract:
Pneumococcal and Salmonella typhi infections are two major diseases for children in developing countries. For typhoid fever, licensed Vi polysaccharide vaccines are ineffective in children <2-year old. While investigational Vi conjugate vaccines have been shown effective in clinical trials, they are currently only available to restricted areas. Pneumococcal capsular polysaccharide conjugate vaccines are highly effective in children, but suffer from some limitations including cost and limited serotype coverage. We have previously shown that a fusion conjugate vaccine, consisting of pneumococcal fusion protein PsaA and pneumolysoid (PdT) conjugated to a polysaccharide, results in enhanced antibody and CD4+ Th17 cell responses as well as protection against pneumococcal colonization and disease in mice. Here we applied this approach to develop a bivalent vaccine against pneumococcus and S. typhi. Two species-conserved pneumococcal antigens (SP1572 or SP2070) were fused to the nonhemolytic pneumolysoid PdT. SP1572-PdT was then conjugated to Vi polysaccharide and SP2070-PdT was conjugated to the pneumococcal cell wall polysaccharide (CWPS; also conserved). Mice immunized with this bivalent conjugate were protected against pneumococcal colonization and sepsis challenges, and made anti-Vi antibody concentrations higher by 40-fold compared to mice that received equimolar mixtures of the antigens. An enhanced killing of Vi-bearing Salmonellae in vitro was demonstrated from plasma of mice that received the fusion conjugate but not the mixture of antigens. Our results support further evaluation of this bivalent immunogen for the prevention of pneumococcal colonization and disease, and of typhoid fever.
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