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Recent Advances in Novel Pneumococcal Vaccines

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Infectious Diseases".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 30349

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Dr. Jose Enrique Yuste

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Spanish Pneumococcal Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain
Interests: epidemiology; vaccines; antibiotic resistance; respiratory pathogens; biofilms
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Special Issue Information

Dear Colleagues,

Prevention of pneumonia and invasive disease caused by Streptococcus pneumoniae is essential to avoid the high morbidity and mortality rates worldwide by this devastating human pathogen. Current vaccines against pneumococcus are based in capsular polysaccharides conjugated or not to a carrier protein. Despite the effectiveness of these vaccines reducing the burden of disease and controlling indirectly, antibiotic resistance, serotype replacement is one of their main limitations due to the high variability of serotypes of this bacterium. New broader pneumococcal conjugate vaccines (PCVs) may partially solve this problem for a limited period of time although, alternative vaccines based in conserved and immunogenic protein antigens, DNA-based vaccines, whole cell vaccines and others preventive options that may increase the protection coverage are needed. This Special Issue will focus in the characterization of novel vaccines to prevent pneumococcal infections including the evaluation of the host immune response of newer PCVs and non-capsular based vaccines. The impact of vaccines reducing pneumococcal carriage and disease would be of interest. Contributions in the areas of microbiology, immunology and clinical epidemiology related to novel pneumococcal vaccines are welcome.

Dr. Jose Yuste
Guest Editor

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Keywords

Pneumococcal vaccines
protein antigens
serotype replacement
carriage
immune response
complement
opsonophagocytosis
antibodies
S. pneumoniae

Published Papers (10 papers)

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Research

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16 pages, 2712 KiB

Open AccessArticle

Protective Effect of Nasal Colonisation with ∆cps/piaA and ∆cps/proABCStreptococcus pneumoniae Strains against Recolonisation and Invasive Infection

by Elisa Ramos-Sevillano, Giuseppe Ercoli, José Afonso Guerra-Assunção, Philip Felgner, Rafael Ramiro de Assis, Rie Nakajima, David Goldblatt, Kevin Kweku Adjei Tetteh, Robert Simon Heyderman, Stephen Brian Gordon, Daniela Mulari Ferreria and Jeremy Stuart Brown

Vaccines 2021, 9(3), 261; https://doi.org/10.3390/vaccines9030261 - 15 Mar 2021

Cited by 2 | Viewed by 2912

Abstract

Rationale: Nasopharyngeal administration of live virulence-attenuated Streptococcus pneumoniae strains is a potential novel preventative strategy. One target for creating reduced virulence S. pneumoniae strains is the capsule, but loss of the capsule reduces the duration of S. pneumoniae colonisation in mice which could impair protective efficacy against subsequent infection. Objectives: To assess protective efficacy of nasopharyngeal administration of unencapsulated S. pneumoniae strains in murine infection models. Methods: Strains containing cps locus deletions combined with the S. pneumoniae virulence factors psaA (reduces colonisation) or proABC (no effect on colonisation) were constructed and their virulence phenotypes and ability to prevent recolonisation or invasive infection assessed using mouse infection models. Serological responses to colonisation were compared between strains using ELISAs, immunoblots and 254 S. pneumoniae protein antigen array. Measurements and Main Results: The ∆cps/piaA and ∆cps/proABC strains were strongly attenuated in virulence in both invasive infection models and had a reduced ability to colonise the nasopharynx. ELISAs, immunoblots and protein arrays showed colonisation with either strain stimulated weaker serological responses than the wild type strain. Mice previously colonised with these strains were protected against septicaemic pneumonia but, unlike mice colonised with the wild type strain, not against S. pneumoniae recolonisation. Conclusions: Colonisation with the ∆cps/piaA and ∆cps/proABC strains prevented subsequent septicaemia, but in contrast, to published data for encapsulated double mutant strains they did not prevent recolonisation with S. pneumoniae. These data suggest targeting the cps locus is a less effective option for creating live attenuated strains that prevent S. pneumoniae infections. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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12 pages, 1341 KiB

Open AccessArticle

Impact of Biological Therapies on the Immune Response after Pneumococcal Vaccination in Patients with Autoimmune Inflammatory Diseases

by Patricia Richi, Jose Yuste, Teresa Navío, Laura González-Hombrado, Marina Salido, Israel Thuissard-Vasallo, Ana Jiménez-Díaz, Jesús Llorente, Laura Cebrián, Leticia Lojo, Martina Steiner, Tatiana Cobo, María Dolores Martín, Marta García-Castro, Patricia Castro and Santiago Muñoz-Fernández

Vaccines 2021, 9(3), 203; https://doi.org/10.3390/vaccines9030203 - 28 Feb 2021

Cited by 11 | Viewed by 2979

Abstract

Patients with different autoimmune inflammatory diseases (AIID) on biological therapy are at risk of pneumococcal disease. Adults with inflammatory arthropathies, connective tissue diseases, psoriasis, or inflammatory bowel disease on biological therapy such as anti-TNFα, rituximab, tocilizumab, abatacept, or anakinra were included in this study. Patients completed a protocol combining the pneumococcal vaccines PCV13 and PPV23. Immune response against pneumococcal serotypes 1, 3, 7F, 14, 19A, and 19F were assessed evaluating functional antibodies by an opsonophagocytosis killing assay (OPKA). In this study, 182 patients with AIID completed the sequential vaccination protocol. Patients on etanercept tended to achieve OPKA titers against a larger number of serotypes than the rest of patients on other biological therapies, while adalimumab was associated to a lower number of serotypes with OPKA titers. Rituximab was not associated with a worse response when compared with the rest of biological agents. Not glucocorticoids, nor synthetic disease-modifying antirheumatic drugs, interfered with the immune response. OPKA titers against serotype 3 which is one of the most prevalent, was obtained in 44% of patients, increasing up to 58% in those on etanercept. Hence, almost 50% of patients on biological therapy achieved functional antibodies after the administration of a complete pneumococcal vaccination protocol. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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12 pages, 7358 KiB

Open AccessArticle

Immunization with SP_1992 (DiiA) Protein of Streptococcus pneumoniae Reduces Nasopharyngeal Colonization and Protects against Invasive Disease in Mice

by Antonio J. Martín-Galiano, María S. Escolano-Martínez, Bruno Corsini, Adela G. de la Campa and José Yuste

Vaccines 2021, 9(3), 187; https://doi.org/10.3390/vaccines9030187 - 24 Feb 2021

Cited by 2 | Viewed by 1881

Abstract

Knowledge-based vaccinology can reveal uncharacterized antigen candidates for a new generation of protein-based anti-pneumococcal vaccines. DiiA, encoded by the sp_1992 locus, is a surface protein containing either one or two repeats of a 37mer N-terminal motif that exhibits low interstrain variability. DiiA belongs to the core proteome, contains several conserved B-cell epitopes, and is associated with colonization and pathogenesis. Immunization with DiiA protein via the intraperitoneal route induced a strong IgG response, including different IgG subtypes. Vaccination with DiiA increased bacterial clearance and induced protection against sepsis, conferring 70% increased survival at 48 h post-infection when compared to the adjuvant control. The immunogenic response and survival rates in mice immunized with a truncated DiiA version lacking 119 N-terminal residues were remarkably lower, confirming the relevance of the repeat zone in the immunoprotection by DiiA. Intranasal immunization of mice with the entire recombinant protein elicited mucosal IgG and IgA responses that reduced bacterial colonization of the nasopharynx, confirming that this protein might be a vaccine candidate for reducing the carrier rate. DiiA constitutes an example of how functionally unannotated proteins may still represent promising candidates that can be used in prophylactic strategies against the pneumococcal carrier state and invasive disease. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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15 pages, 2462 KiB

Open AccessArticle

Vaccination with LytA, LytC, or Pce of Streptococcus pneumoniae Protects against Sepsis by Inducing IgGs That Activate the Complement System

by Bruno Corsini, Leire Aguinagalde, Susana Ruiz, Mirian Domenech and Jose Yuste

Vaccines 2021, 9(2), 186; https://doi.org/10.3390/vaccines9020186 - 23 Feb 2021

Cited by 3 | Viewed by 2642

Abstract

The emergence of non-vaccine serotypes of Streptococcus pneumoniae after the use of vaccines based in capsular polysaccharides demonstrates the need of a broader protection vaccine based in protein antigens and widely conserved. In this study, we characterized three important virulence factors of S. pneumoniae namely LytA, LytC, and Pce as vaccine candidates. These proteins are choline-binding proteins that belong to the cell wall hydrolases’ family. Immunization of mice with LytA, LytC, or Pce induced high titers of immunoglobulins G (IgGs) of different subclasses, with IgG1, IgG2a, and IgG2b as the predominant immunoglobulins raised. These antibodies activated the classical pathway of the complement system by increasing the recognition of C1q on the surface of pneumococcal strains of different serotypes. Consequently, the key complement component C3 recognized more efficiently these strains in the presence of specific antibodies elicited by these proteins, activating, therefore, the phagocytosis. Finally, a mouse sepsis model of infection was established, confirming that vaccination with these proteins controlled bacterial replication in the bloodstream, increasing the survival rate. Overall, these results demonstrate that LytA, LytC, and Pce can be protein antigens to be contained in a future universal vaccine against S. pneumoniae. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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10 pages, 1031 KiB

Open AccessArticle

Evolution, Clinical and Microbiological Characteristics of Invasive Pneumococcal Disease since the Introduction of the Pneumococcal Conjugate Vaccine 13-Valent in Adults over 18 Years Old

by Juan Buades, Ines Losada, Juan González-Moreno, Maria Peñaranda, Laia Vilaplana, Nuria Roda, Adelaida Rey, Adrian Rodriguez, Margarita Garau, Enrique Ruiz de Gopegui, Antoni Serra, Juan Saurina and Antoni Payeras

Vaccines 2021, 9(2), 93; https://doi.org/10.3390/vaccines9020093 - 27 Jan 2021

Cited by 3 | Viewed by 2220

Abstract

Invasive pneumococcal disease (IPD) presents high mortality in the population at risk. The aim of this work is to know the evolution, clinical and microbiological characteristics of IPD in the adult population of Majorca, since the introduction of a public funded program for pneumococcal conjugate vaccine (PCV-13) in the pediatric population in the Balearic Islands in 2016. For this purpose, a retrospective multicenter study was carried out in which all episodes of IPD in adult patients from the four hospitals of the public health system of Majorca were included, comparing the periods between 2012 and 2015 and between 2016 and 2019. Clinical variables, serotypes and antibiotic sensitivity were collected. There were 498 cases of IPD; 56.8% were male with a mean age of 67 (standard deviation: 16). Most infections were bacterial pneumonias (73.7%). Of the total cases, 264 (53%) presented complications. Of the 498 cases, 351 strains were obtained, of which 145 (41.3%) belong to vaccinal serotypes (included in the PCV-13 vaccine) and 206 (58.7%) to non-vaccinal serotypes (not included in the PCV-13 vaccine). The percentage of IPD caused by vaccinal serotypes was lower in the second period (47.8% vs. 34.5%; p = 0.012). Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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13 pages, 434 KiB

Open AccessArticle

Impact of Pneumococcal Vaccination in the Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy Children of the Murcia Region in Spain

by Santiago Alfayate Miguélez, Genoveva Yague Guirao, Ana I. Menasalvas Ruíz, Manuel Sanchez-Solís, Mirian Domenech Lucas, Fernando González Camacho, M. Mar Ortíz Romero, Pilar Espejo García, Carmen Guerrero Gómez, Antonio Iofrío de Arce, Laura Moreno Parrado, Rosa M. Sánchez Andrada, Eva Cascales Alcolea, Sebastián Lorente García, Pedro Paredes Reyes, Ángela Casquet Barceló, M. Luisa López Yepes, Juan José Vigueras Abellán, Gonzalo Sanz Mateo and Murcian Pneumococcal Study Group

Vaccines 2021, 9(1), 14; https://doi.org/10.3390/vaccines9010014 - 28 Dec 2020

Cited by 16 | Viewed by 3988

Abstract

Background: An epidemiological study of Streptococcus pneumoniae nasopharyngeal carriage in healthy children was carried out five years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Objectives: Study the impact of pediatric vaccination with PCV13, and other associated epidemiological factors on the status of nasopharyngeal carriage, the circulating pneumococcal serotypes, and the antibiotic susceptibility to more frequently used antibiotics. Methods: A multi-center study was carried out in Primary Health Care, which included 1821 healthy children aged 1 to 4 years old. All isolates were sent to the Spanish Pneumococcal Reference Laboratory for serotyping and antimicrobial susceptibility testing. Results: At least one dose of PCV13 had been received by 71.9% of children and carriage pneumococcal prevalence was 19.7%. The proportion of PCV13 serotypes was low (14.4%), with an observed predominance of non-vaccine serotypes, 23B, 11A, 10A, 35B/F, and 23A were the five most frequent. A high rate of resistance to penicillin, erythromycin, and trimethoprim sulfamethoxazole was found. Conclusions: A low proportion of PCV13 serotypes were detected, confirming the impact of pediatric vaccination for reducing the serotypes vaccine carriage. High resistance rates to clinically important antibiotics were observed. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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Review

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13 pages, 260 KiB

Open AccessReview

Pneumococcal Vaccination in Immunocompromised Hosts: An Update

by Claire Froneman, Peter Kelleher and Ricardo J. José

Vaccines 2021, 9(6), 536; https://doi.org/10.3390/vaccines9060536 - 21 May 2021

Cited by 5 | Viewed by 2443

Abstract

Infections with the pathogen, Streptococcus pneumoniae, are a common cause of morbidity and mortality worldwide. It particularly affects those at the extremes of age and immunocompromised individuals. Preventing pneumococcal disease is paramount in at risk individuals, and pneumococcal vaccination should be offered. [...] Read more.

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

17 pages, 1767 KiB

Open AccessReview

Multi-Valent Protein Hybrid Pneumococcal Vaccines: A Strategy for the Next Generation of Vaccines

by Ninecia R. Scott, Beth Mann, Elaine I. Tuomanen and Carlos J. Orihuela

Vaccines 2021, 9(3), 209; https://doi.org/10.3390/vaccines9030209 - 2 Mar 2021

Cited by 13 | Viewed by 5288

Abstract

Streptococcus pneumoniae (Spn) is a bacterial pathogen known to colonize the upper respiratory tract and cause serious opportunistic diseases such as pneumonia, bacteremia, sepsis and meningitis. As a consequence, millions of attributable deaths occur annually, especially among infants, the elderly and immunocompromised individuals. Although current vaccines, composed of purified pneumococcal polysaccharide in free form or conjugated to a protein carrier, are widely used and have been demonstrated to be effective in target groups, Spn has continued to colonize and cause life-threatening disease in susceptible populations. This lack of broad protection highlights the necessity of improving upon the current “gold standard” pneumococcal vaccines to increase protection both by decreasing colonization and reducing the incidence of sterile-site infections. Over the past century, most of the pneumococcal proteins that play an essential role in colonization and pathogenesis have been identified and characterized. Some of these proteins have the potential to serve as antigens in a multi-valent protein vaccine that confers capsule independent protection. This review seeks to summarize the benefits and limitations of the currently employed vaccine strategies, describes how leading candidate proteins contribute to pneumococcal disease development, and discusses the potential of these proteins as protective antigens—including as a hybrid construct. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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19 pages, 410 KiB

Open AccessReview

Pneumococcal Choline-Binding Proteins Involved in Virulence as Vaccine Candidates

by Julio Sempere, Mirella Llamosí, Idoia del Río Menéndez, Beatriz López Ruiz, Mirian Domenech and Fernando González-Camacho

Vaccines 2021, 9(2), 181; https://doi.org/10.3390/vaccines9020181 - 20 Feb 2021

Cited by 10 | Viewed by 3049

Abstract

Streptococcus pneumoniae is a pathogen responsible for millions of deaths worldwide. Currently, the available vaccines for the prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV-23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes (up to 100 different serotypes have been identified) and are unable to protect against non-vaccine serotypes and non-encapsulated pneumococci. The emergence of antibiotic-resistant non-vaccine serotypes after these vaccines is an increasing threat. Therefore, there is an urgent need to develop new pneumococcal vaccines which could cover a wide range of serotypes. One of the vaccines most characterized as a prophylactic alternative to current PPV-23 or PCVs is a vaccine based on pneumococcal protein antigens. The choline-binding proteins (CBP) are found in all pneumococcal strains, giving them the characteristic to be potential vaccine candidates as they may protect against different serotypes. In this review, we have focused the attention on different CBPs as vaccine candidates because they are involved in the pathogenesis process, confirming their immunogenicity and protection against pneumococcal infection. The review summarizes the major contribution of these proteins to virulence and reinforces the fact that antibodies elicited against many of them may block or interfere with their role in the infection process. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

Other

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5 pages, 214 KiB

Open AccessViewpoint

Pneumococcal Disease Prevention: Are We on the Right Track?

by Nicola Principi and Susanna Esposito

Vaccines 2021, 9(4), 305; https://doi.org/10.3390/vaccines9040305 - 24 Mar 2021

Cited by 6 | Viewed by 1964

Abstract

The history of Streptococcus pneumoniae diseases dramatically changed with the introduction into the immunization schedule of infants and children of the first pneumococcal conjugate vaccine, the one containing 7 (PCV7) of the most common pneumococcal serotypes (STs) causing invasive pneumococcal diseases (IPDs). Where PCV7 was largely used, incidence of both IPDs and non-invasive pneumococcal diseases (nIPDs) in vaccinated children and in unvaccinated subjects of any age, mainly the elderly, significantly decreased. Unfortunately, the impact of PCV7 administration was slightly lower than expected, as the reduction in infections due to vaccine serotypes (STs) was accompanied by a significant increase in the number of IPDs and nIPDs due to STs not included in the vaccine. To overcome this problem, two PCVs containing 10 (PCV10) and 13 (PCV13) STs, chosen among those emerging, were developed and licensed. However, ST replacement occurred again. Moreover, the new PCVs showed little effectiveness in the prevention of infection due to non-encapsulated STs and to ST3. Next-generation S. pneumoniae vaccines able to prevent pneumococcal infections regardless of infecting ST are urgently needed. For the moment, the use of available PCVs remains fundamental because their benefits far outweigh any concerns for emerging STs. Full article

(This article belongs to the Special Issue Recent Advances in Novel Pneumococcal Vaccines)

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