Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies

Oliveira, Giuliana S.; Oliveira, Maria Leonor S.; Miyaji, Eliane N.; Rodrigues, Tasson C.

doi:10.3390/vaccines9111338

Cited by 26 publications

(25 citation statements)

References 145 publications

(177 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Serotype replacement following administration of current PCVs has not only driven the development of next generation, extended PCVs, which contain CPS derived Musher et al Pneumonia (2022) 14:5 from emerging, opportunistic serotypes of the pathogen [81,82], but also the formulation of novel vaccines based on recombinant pneumococcal proteins [83][84][85][86][87]. This latter strategy hinges on the immunogenicity of highly conserved, broadly serotype-independent pneumococcal virulence factors, particularly surface adhesins.…”

Section: Recombinant Protein-based Pneumococcal Vaccinesmentioning

confidence: 99%

See 1 more Smart Citation

The remarkable history of pneumococcal vaccination: an ongoing challenge

2022

View full text Add to dashboard Cite

Although it varies with age and geographical distribution, the global burden of infection with Streptococcus pneumoniae (pneumococcus) remains considerable. The elderly, and younger adults with comorbid conditions, are at particularly high risk of pneumococcal infection, and this risk will increase as the population ages. Vaccination should be the backbone of our current strategies to deal with this infection.Main body: This manuscript reviews the history of the development of pneumococcal vaccines, and the impact of different vaccines and vaccination strategies over the past 111 years. It documents the early years of vaccine development in the gold mines of South Africa, when vaccination with killed pneumococci was shown to be effective, even before the recognition that different pneumococci were antigenically distinct. The development of type-specific vaccines, still with whole killed pneumococci, showed a high degree of efficacy. The identification of the importance of the pneumococcal capsule heralded the era of vaccination with capsular polysaccharides, although with the advent of penicillin, interest in pneumococcal vaccine development waned. The efforts of Austrian and his colleagues, who documented that despite penicillin therapy, patients still died from pneumococcal infection in the first 96 h, ultimately led to the licensing first of a 14-valent pneumococcal polysaccharide in 1977 followed by the 23-valent pneumococcal polysaccharide in 1983. The principal problem with these, as with other polysaccharide vaccines, was that that they failed to immunize infants and toddlers, who were at highest risk for pneumococcal disease. This was overcome by chemical linking or conjugation of the polysaccharide molecules to an immunogenic carrier protein. Thus began the era of pneumococcal conjugate vaccine (PCV), starting with PCV7, progressing to PCV10 and PCV13, and, most recently, PCV15 and PCV20. However, these vaccines remain serotype specific, posing the challenge of new serotypes replacing vaccine types. Current research addresses serotype-independent vaccines which, so far, has been a challenging and elusive endeavor.Conclusion: While there has been enormous progress in the development of pneumococcal vaccines during the past century, attempts to develop a vaccine that will retain its efficacy for most pneumococcal serotypes are ongoing.

show abstract

Section: Recombinant Protein-based Pneumococcal Vaccinesmentioning

confidence: 99%

“…These include an earlier study, which described an attenuated Salmonella DNA vaccine that delivered recombinant PspA, which, in turn, protected mice experimentally infected with influenza virus against secondary pneumococcal infection [ 101 ]. Future innovations include the possible development of messenger RNA (mRNA) vaccines [ 86 ].…”

Section: Introductionmentioning

confidence: 99%

The remarkable history of pneumococcal vaccination: an ongoing challenge

2022

View full text Add to dashboard Cite

show abstract

“…S. pneumoniae is an important pathogen that cause several diseases ranging from sinusitis and otitis media to life-threatening diseases such as pneumonia, bacteremia and meningitis 516 . In order to control pneumococcal disease, several pneumococcal conjugated vaccines (PCVs, 53 ) have been approved for S. pneumoniae infection prevention since 2000.…”

Section: Other Carbohydrate-based Drugsmentioning

confidence: 99%

“…The promotion and application of these vaccines remarkably declined the disease burden of S. pneumoniae ( Supporting Information Fig. S8 ) 516 .…”

Section: Other Carbohydrate-based Drugsmentioning

confidence: 99%

Carbohydrate-based drugs launched during 2000−2021

Cao

Jiao

et al. 2022

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

“…Since the first commercial usage of pneumococcal vaccines in the 1980s, the incidence of pneumonia has decreased significantly ( 10 ). With the ongoing introduction of multivalent PCVs, vaccination and secondary herd protection of nonvaccinated populations has become a public health benefit ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Construction and protective efficacy of a novel Streptococcus pneumoniae fusion protein vaccine NanAT1-TufT1-PlyD4

et al. 2022

View full text Add to dashboard Cite

During the past decades, with the implementation of pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCVs), a dramatic reduction in vaccine type diseases and transmissions has occurred. However, it is necessary to develop a less expensive, serotype-independent pneumococcal vaccine due to the emergence of nonvaccine-type pneumococcal diseases and the limited effect of vaccines on colonization. As next-generation vaccines, conserved proteins, such as neuraminidase A (NanA), elongation factor Tu (Tuf), and pneumolysin (Ply), are promising targets against pneumococcal infections. Here, we designed and constructed a novel fusion protein, NanAT1-TufT1-PlyD4, using the structural and functional domains of full-length NanA, Tuf and Ply proteins with suitable linkers based on bioinformatics analysis and molecular cloning technology. Then, we tested whether the protein protected against focal and lethal pneumococcal infections and examined its potential protective mechanisms. The fusion protein NanAT1-TufT1-PlyD4 consists of 627 amino acids, which exhibits a relatively high level of thermostability, high stability, solubility and a high antigenic index without allergenicity. The purified fusion protein was used to subcutaneously immunize C57BL/6 mice, and NanAT1-TufT1-PlyD4 induced a strong and significant humoral immune response. The anti-NanAT1-TufT1-PlyD4 specific IgG antibody assays increased after the first immunization and reached the highest value at the 35th day. The results from in vitro experiments showed that anti-NanAT1-TufT1-PlyD4 antisera could inhibit the adhesion of Streptococcus pneumoniae (S. pneumoniae) to A549 cells. In addition, immunization with NanAT1-TufT1-PlyD4 significantly reduced S. pneumoniae colonization in the lung and decreased the damage to the lung tissues induced by S. pneumoniae infection. After challenge with a lethal dose of serotype 3 (NC_WCSUH32403), a better protection effect was observed with NanAT1-TufT1-PlyD4-immunized mice than with the separate full-length proteins and the adjuvant control; the survival rate was 50%, which met the standard of the marketed vaccine. Moreover, we showed that the humoral immune response and the Th1, Th2 and Th17-cellular immune pathways are involved in the immune protection of NanAT1-TufT1-PlyD4 to the host. Collectively, our results support that the novel fusion protein NanAT1-TufT1-PlyD4 exhibits extensive immune stimulation and is effective against pneumococcal challenges, and these properties are partially attributed to humoral and cellular-mediated immune responses.

show abstract

Pneumococcal Vaccines: Past Findings, Present Work, and Future Strategies

Cited by 26 publications

References 145 publications

The remarkable history of pneumococcal vaccination: an ongoing challenge

The remarkable history of pneumococcal vaccination: an ongoing challenge

Carbohydrate-based drugs launched during 2000−2021

Construction and protective efficacy of a novel Streptococcus pneumoniae fusion protein vaccine NanAT1-TufT1-PlyD4

Contact Info

Product

Resources

About