Combination Vaccines

Combination vaccines have been around since 1945 (trivalent influenza vaccine) and they combine either different serotypes of one microorganism (e.g., influenza or pneumococcal vaccines) or different microorganisms (e.g., DTP combinations). Potential chemical and physical interactions, unpredictable immunological interactions, and in one instance: increased AE, increasing likelihood of production failures, and reduced flexibility of a vaccination program are challenges for developing combination vaccines. With an increasing number of new vaccines for protecting the very young, DTaP- and DTwP-based combinations have become the cornerstone of pediatric vaccination programs around the globe since the mid-1990s. Live vaccine combinations include MR, MMR, and MMRV combinations as well as (trivalent) OPV. Combination vaccines for travelers include HAV-HBV combination and HAV-Ty vaccines. Dozens of diverse combination vaccine products are licensed today around the globe, some of them only in single countries to cover specific local needs. Combination vaccines have been shown to result in increased acceptance, completion and compliance with vaccination programs; in addition, they offer simplified logistics, reduce administration errors, reduce the number of medical visits and cost for the individual as well as for society, among other benefits.

Review of global use of licensed vaccines and development of new vaccines for the prevention of pneumococcal infection

Streptococcus pneumoniae infection is the most common cause of high morbidity and mortality among children under 5 years of age, immunocompromised people, and the elderly. Despite significant success, the approved pneumococcal conjugate and polysaccharide vaccines are of limited efficacy, providing protection against a small fraction of the known pneumococcal serotypes. The rapid spread of multidrug-resistant strains exacerbates the global challenge of treating infection caused by S. pneumoniae. At the same time, the emerging new strains dictate the need to include new serotypes into vaccines. In view of this, further improvement of vaccines for the prevention of pneumococcal infections is an urgent task. The aim of this study was to review advances in the development of polysaccharide, conjugate, whole-cell pneumococcal vaccines, as well as vaccines based on protein antigens and vaccines with an antigen delivery system. Genomics and proteomics data have helped to improve approaches to the creation of polysaccharide and protein-based vaccines, as well as whole-cell vaccines with the potential for population prophylactic coverage against various pneumococcal serotypes that are not included in the licensed pneumococcal vaccines. The method of antigen delivery to the cell is of great importance in the development of vaccines. The most promising strategy for improving pneumococcal vaccines is the creation of vaccines based on bacterium-like or synthetic particles carrying several antigens, including pneumococcal surface proteins. In conclusion, it should be noted that top-priority vaccines are those that provide a wide range of protection against circulating pneumococcal serotypes and, in addition to eliciting a systemic immune response, also induce local immunity.

Pneumococcal serotypes causing non-invasive pneumonia in adults from a South Indian tertiary care hospital and the impact of the newer conjugate vaccines

Background. Streptococcus pneumoniae is the leading cause of community-acquired pneumonia (CAP) in adults. Ageing, chronic conditions and comorbidities are important risk factors for pneumococcal pneumonia. Purpose. There is lack of data on the pneumococcal serotypes causing non-invasive pneumonia in India. This study aims to determine the prevalent pneumococcal serotypes causing non-invasive pneumonia, the associated comorbidities, and the coverage of both the available pneumococcal vaccines in India and conjugate vaccines that are currently undergoing clinical trials. Methods. A total of 280 subjects (aged >16 years) who had clinical symptoms correlating with radiological findings for non-invasive bacteremic pneumonia and microbiological evidence of S. pneumoniae between 2018 and 2020 were included. The clinical, demographic, radiological and microbiological findings were retrieved from the Hospital Information System (HIS). Results. The common serotypes in order of prevalence were 19F, 9V, 23F, 6B, 11A, 13, 34, 10A, 19A and 6A. The predominant non-vaccine serotypes were 13, 34, 35B, 31 and 16F. The associated radiological findings were pneumonic consolidation and multi-lobar involvement. Other coinfected bacterial pathogens included H. influenzae, S. aureus, K. pneumoniae and P. aeruginosa. Conclusion. The pneumococcal vaccines: PCV10/GSK, PCV10/SII, PCV13, PCV15, PCV20 and PPSV23 provide an overall serotype coverage of 36, 41, 47, 48, 61 and 69 %, respectively of S. pneumoniae causing non-invasive pneumonia in South India. Increasing catch-up vaccination using PCV10(SII) in pre-school children could have a more significant impact on reducing pneumococcal pneumonia in adults (>50 years) in terms of increased herd immunity at an affordable cost.

If Not Now, When? Nonserotype Pneumococcal Protein Vaccines

The sudden emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have greatly accelerated the adoption of novel vaccine strategies, which otherwise would have likely languished for years. In this light, vaccines for certain other pathogens could certainly benefit from reconsideration. One such pathogen is Streptococcus pneumoniae (pneumococcus), an encapsulated bacterium that can express >100 antigenically distinct serotypes. Current pneumococcal vaccines are based exclusively on capsular polysaccharide—either purified alone or conjugated to protein. Since the introduction of conjugate vaccines, the valence of pneumococcal vaccines has steadily increased, as has the associated complexity and cost of production. There are many pneumococcal proteins invariantly expressed across all serotypes, which have been shown to induce robust immune responses in animal models. These proteins could be readily produced using recombinant DNA technology or by mRNA technology currently used in SARS-CoV-2 vaccines. A door may be opening to new opportunities in affordable and broadly protective vaccines.

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

The importance of Streptococcus pneumoniae has been well established. These bacteria can colonize infants and adults without symptoms, but in some cases can spread, invade other tissues and cause disease with high morbidity and mortality. The development of pneumococcal conjugate vaccines (PCV) caused an enormous impact in invasive pneumococcal disease and protected unvaccinated people by herd effect. However, serotype replacement is a well-known phenomenon that has occurred after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) and has also been reported for other PCVs. Therefore, it is possible that serotype replacement will continue to occur even with higher valence formulations, but the development of serotype-independent vaccines might overcome this problem. Alternative vaccines are under development in order to improve cost effectiveness, either using proteins or the pneumococcal whole cell. These approaches can be used as a stand-alone strategy or together with polysaccharide vaccines. Looking ahead, the next generation of pneumococcal vaccines can be impacted by the new technologies recently approved for human use, such as mRNA vaccines and viral vectors. In this paper, we will review the advantages and disadvantages of the addition of new polysaccharides in the current PCVs, mainly for low- and middle-income countries, and we will also address future perspectives.

High-Throughput Mutagenesis and Cross-Complementation Experiments Reveal Substrate Preference and Critical Residues of the Capsule Transporters in Streptococcus pneumoniae

All licensed pneumococcal vaccines target the capsular polysaccharide (CPS). This layer is highly variable and is important for virulence in many bacterial pathogens.