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1.
BMC Infect Dis ; 22(1): 507, 2022 May 31.
Article in English | MEDLINE | ID: covidwho-1951094

ABSTRACT

BACKGROUND: This study aimed to identify differences and similarities among adolescents and parents in various psychosocial factors influencing meningococcal ACWY (MenACWY) vaccination acceptance. Besides, the impact of the Covid-19 pandemic was assessed as well as resulting organizational adjustments. METHODS: We conducted a cross-sectional survey among adolescents that attended the appointment for the MenACWY vaccination in South Limburg between May and June 2020, and their parents. Independent t-tests and χ2 test were performed to explore differences in psychosocial and organisational factors between adolescents and parents. RESULTS: In total, 592 adolescents (20%) and 1197 parents (38%) filled out the questionnaire. Adolescents scored lower on anticipated negative affect towards MenACWY vaccination refusal [t (985.688) = - 9.32; ρ < 0.001], moral norm towards MenACWY vaccination acceptance [t (942.079) = - 10.38; ρ < 0.001] and knowledge about the MenACWY vaccination and meningococcal disease [t (1059.710) = - 11.24; ρ < 0.001]. Both adolescents and parents reported a social norm favouring accepting childhood vaccinations, but adolescent scored higher [t (1122.846) = 23.10; ρ < 0.001]. The Covid-19 pandemic did barely influence the decision to accept the MenACWY vaccination. Only 6% of the participants indicated that Covid-19 influenced their decision. In addition, the individual vaccination appointment was rated very positive. Most adolescents (71.5%) and parents (80.6%) prefer future vaccinations to be offered individually rather than having mass vaccinations sessions. CONCLUSIONS: This study provides an indication of which psychosocial and organisational factors should be addressed in future MenACWY vaccination campaigns. Individual vaccination appointments for adolescents should be considered, taking the costs and logistical barriers into account.


Subject(s)
COVID-19 , Neisseria meningitidis , Adolescent , COVID-19/epidemiology , COVID-19/prevention & control , Cross-Sectional Studies , Humans , Meningococcal Vaccines , Pandemics , Parents , Vaccination , Vaccines, Conjugate
2.
Vaccine ; 40(15): 2274-2281, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1937280

ABSTRACT

We evaluated compliance to the ACIP pneumococcal vaccination recommendations issued in 2014 for adults aged ≥ 65 years and in 2012 for adults with high-risk (HR) conditions. The MarketScan® Commercial and Medicare Supplemental databases (January 2007-June 2019) were used to identify the cohorts of interest. Analyses for adults aged ≥ 65 years were adjusted to account for missing vaccination history. Two HR cohorts were identified. The HR1 cohort included patients with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid leak, or cochlear implant. The HR2 cohort included patients with chronic heart, lung, or liver disease; diabetes mellitus; alcoholism; cirrhosis; or cigarette smoking. Full compliance for those aged ≥ 65 years or in the HR1 cohort was defined as receipt of PCV13 and PPSV23, and partial compliance was defined as receipt of PCV13 or PPSV23. For those in the HR2 cohort, full compliance was defined as receipt of PPSV23. Annual compliance rates were estimated using the Kaplan-Meier method. Among those aged ≥ 65 years, partial compliance at 4 years post index was 53% and full compliance was 17% in adjusted analyses. In subjects ≥ 65 years receiving the first vaccination, 42% received the second vaccination by year 4. For the HR1 cohort, partial compliance was 19% and full compliance was 5% at 6 years post index date. For the HR2 cohort, full compliance was 20% at 6 years, with the highest rate in patients with diabetes (27%) and the lowest rate in patients with alcoholism (8%). Additional efforts are needed to maximize compliance to the ACIP pneumococcal vaccine recommendations among adults ≥ 65 years of age and adults with HR conditions including streamlined recommendations and single-dose vaccines. These efforts may subsequently reduce the incidence and burden of pneumococcal disease.


Subject(s)
Advisory Committees , Pneumococcal Infections , Aged , Humans , Immunocompromised Host , Medicare , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , United States , Vaccination , Vaccines, Conjugate
3.
ACS Infect Dis ; 8(7): 1367-1375, 2022 Jul 08.
Article in English | MEDLINE | ID: covidwho-1908085

ABSTRACT

With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.


Subject(s)
COVID-19 , SARS-CoV-2 , Adjuvants, Immunologic/pharmacology , Adjuvants, Pharmaceutic , Animals , COVID-19/prevention & control , Humans , Mice , Mice, Inbred BALB C , Spike Glycoprotein, Coronavirus , Toll-Like Receptor 7 , Vaccines, Conjugate
4.
J Med Chem ; 65(3): 2558-2570, 2022 02 10.
Article in English | MEDLINE | ID: covidwho-1895561

ABSTRACT

Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are the best approach to successfully combat the COVID-19 pandemic. The receptor-binding domain (RBD) of the viral spike protein is a major target to develop candidate vaccines. α-Galactosylceramide (αGalCer), a potent invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated to the N-terminus of the RBD to form an adjuvant-protein conjugate, which was anchored on the liposome surface. This is the first time that an iNKT cell agonist was conjugated to the protein antigen. Compared to the unconjugated RBD/αGalCer mixture, the αGalCer-RBD conjugate induced significantly stronger humoral and cellular responses. The conjugate vaccine also showed effective cross-neutralization to all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results suggest that the self-adjuvanting αGalCer-RBD has great potential to be an effective COVID-19 vaccine candidate, and this strategy might be useful for designing various subunit vaccines.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/therapy , Galactosylceramides/therapeutic use , Peptide Fragments/therapeutic use , SARS-CoV-2/immunology , Vaccines, Conjugate/therapeutic use , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/therapeutic use , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Female , Galactosylceramides/chemistry , Galactosylceramides/immunology , Immunity, Humoral/drug effects , Immunity, Innate/drug effects , Interferon-gamma/metabolism , Liposomes/chemistry , Liposomes/immunology , Liposomes/therapeutic use , Mice, Inbred BALB C , Peptide Fragments/chemistry , Peptide Fragments/immunology , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/therapeutic use , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/immunology
5.
Am Fam Physician ; 105(6): 625-630, 2022 06 01.
Article in English | MEDLINE | ID: covidwho-1888309

ABSTRACT

Community-acquired pneumonia (CAP) is a common condition with a hospitalization rate of about 2% in people 65 years or older and is associated with a 30-day mortality rate of 6% in hospitalized patients. In studies conducted before the COVID-19 pandemic, a bacterial pathogen was identified in 11% of patients, a viral pathogen in 23% of patients, and no organism in 62% of patients. Certain signs and symptoms can be helpful in diagnosing CAP and selecting imaging studies. Diagnosis is usually made with a combination of history, physical examination, and findings on chest radiography, lung ultrasonography, or computed tomography. Procalcitonin measurement is not recommended. CRB-65 (confusion, respiratory rate, blood pressure, 65 years of age) is a well-validated risk stratification tool in the primary care setting and does not require laboratory testing. For outpatients without comorbidities, treatment with amoxicillin, doxycycline, or a macrolide is recommended (the latter only in areas where pneumococcal resistance to macrolides is less than 25%). In outpatients with comorbidities and inpatients with nonsevere pneumonia, a combination of a beta-lactam or third-generation cephalosporin plus a macrolide, or monotherapy with a respiratory fluoroquinolone is recommended. Patients should be treated for methicillin-resistant Staphylococcus aureus or Pseudomonas infection only if they present with risk factors for those pathogens. All adults 65 years or older or those 19 to 64 with underlying conditions should receive the 20-valent pneumococcal conjugate vaccine alone or the 15-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine one year later. The 13-valent pneumococcal conjugate vaccine is no longer recommended for routine administration. The Centers for Disease Control and Prevention recommends vaccination against influenza and SARS-CoV-2 viruses for all adults.


Subject(s)
COVID-19 , Community-Acquired Infections , Methicillin-Resistant Staphylococcus aureus , Pneumonia , Adult , Anti-Bacterial Agents/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Humans , Macrolides , Pandemics , Pneumonia/drug therapy , SARS-CoV-2 , Vaccines, Conjugate
6.
Front Cell Infect Microbiol ; 12: 866186, 2022.
Article in English | MEDLINE | ID: covidwho-1865449

ABSTRACT

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [erm(B) and mef(A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef(A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm(B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru.


Subject(s)
COVID-19 , Pneumococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Drug Resistance, Bacterial , Humans , Infant , Macrolides/pharmacology , Pandemics , Peru/epidemiology , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Vaccines, Conjugate
7.
Rev Esp Quimioter ; 35 Suppl 1: 104-110, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1836624

ABSTRACT

Adults with lung diseases, comorbidities, smokers, and elderly are at risk of lung infections and their consequences. Community-acquired pneumonia happen in more than 1% of people each year. Possible pathogens of community-acquired pneumonia include viruses, pneumococcus and atypicals. The CDC recommend vaccination throughout life to provide immunity, but vaccination rates in adults are poor. Tetravalent and trivalent influenza vaccine is designed annually during the previous summer for the next season. The available vaccines include inactivated, adjuvant, double dose, and attenuated vaccines. Their efficacy depends on the variant of viruses effectively responsible for the outbreak each year, and other reasons. Regarding the pneumococcal vaccine, there coexist the old polysaccharide 23-valent vaccine with the new conjugate 10-valent and 13-valent conjugate vaccines. Conjugate vaccines demonstrate their usefulness to reduce the incidence of pneumococcal pneumonia due to the serotypes present in the vaccine. Whooping cough is still present, with high morbidity and mortality rates in young infants. Adult's pertussis vaccine is available, it could contribute to the control of whooping cough in the most susceptible, but it is not present yet in the calendar of adults around the world. About 10 vaccines against SARS-CoV-2 have been developed in a short time, requiring emergency use authorization. A high rate of vaccination was observed in most of the countries. Booster doses became frequent after the loss of effectiveness against new variants. The future of this vaccine is yet to be written.


Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia, Pneumococcal , Whooping Cough , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Community-Acquired Infections/epidemiology , Community-Acquired Infections/prevention & control , Humans , Infant , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Prognosis , SARS-CoV-2 , Vaccination , Vaccines, Conjugate
8.
ACS Chem Biol ; 17(5): 1184-1196, 2022 05 20.
Article in English | MEDLINE | ID: covidwho-1783934

ABSTRACT

Vaccine scaffolds and carrier proteins increase the immunogenicity of subunit vaccines. Here, we developed, characterized, and demonstrated the efficacy of a novel microparticle vaccine scaffold comprised of bacterial peptidoglycan (PGN), isolated as an entire sacculi. The PGN microparticles contain bio-orthogonal chemical handles allowing for site-specific attachment of immunogens. We first evaluated the purification, integrity, and immunogenicity of PGN microparticles derived from a variety of bacterial species. We then optimized PGN microparticle modification conditions; Staphylococcus aureus PGN microparticles containing azido-d-alanine yielded robust conjugation to immunogens. We then demonstrated that this vaccine scaffold elicits comparable immunostimulation to the conventional carrier protein, keyhole limpet hemocyanin (KLH). We further modified the S. aureus PGN microparticle to contain the SARS-CoV-2 receptor-binding domain (RBD)─this conjugate vaccine elicited neutralizing antibody titers comparable to those elicited by the KLH-conjugated RBD. Collectively, these findings suggest that chemically modified bacterial PGN microparticles are a conjugatable and biodegradable microparticle scaffold capable of eliciting a robust immune response toward an antigen of interest.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/prevention & control , Humans , Peptidoglycan , Staphylococcus aureus , Vaccines, Conjugate , Vaccines, Subunit
9.
Adv Sci (Weinh) ; 9(11): e2105378, 2022 04.
Article in English | MEDLINE | ID: covidwho-1680239

ABSTRACT

The SARS-CoV-2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first-generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS-CoV-2 variants as the major target. Here, receptor binding domain (RBD)-conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single-dose and a prime-boost strategy, these RBD-conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS-CoV-2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross-protective NAbs against almost all the notable SARS-CoV-2 variants including the Omicron variant in rhesus macaques by the third re-boost with trivalent vaccines is found. These results suggest that RBD-based monovalent or multivalent nanoparticle vaccines provide a promising second-generation vaccine strategy for SARS-CoV-2 variants.


Subject(s)
COVID-19 , Nanoparticles , Animals , Broadly Neutralizing Antibodies , COVID-19/prevention & control , Macaca mulatta/metabolism , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccines, Conjugate
10.
Chem Commun (Camb) ; 58(13): 2120-2123, 2022 Feb 10.
Article in English | MEDLINE | ID: covidwho-1639577

ABSTRACT

The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam3CSK4-RBD as a vaccine candidate, in which the N-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam3CSK4. This demonstrated that the conjugation of Pam3CSK4 significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam3CSK4-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.


Subject(s)
COVID-19/prevention & control , Lipopeptides/chemistry , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Vaccines, Conjugate/immunology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibody Formation , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , COVID-19/virology , Female , HEK293 Cells , Humans , Macrophages/cytology , Macrophages/immunology , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Protein Binding , Protein Domains/immunology , RAW 264.7 Cells , Recombinant Proteins/biosynthesis , Recombinant Proteins/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/chemistry
11.
J Infect Dis ; 224(Supplement_5): S469-S474, 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1638132

ABSTRACT

Enteric fever continues to impact millions of people who lack adequate access to clean water and sanitation. The typhoid and paratyphoid fever burden in South Asia is broadly acknowledged, but current estimates of incidence, severity, and cost of illness from India are lacking. This supplement addresses this gap in our knowledge, presenting findings from two years of surveillance, conducted at multiple sites between October 2017 and February 2020, in the Surveillance for Enteric Fever in India (SEFI) network. Results provide contemporaneous evidence of high disease burden and cost of illness-the latter borne largely by patients in the absence of universal healthcare coverage in India. Against a backdrop of immediate priorities in the COVID-19 pandemic, these data are a reminder that typhoid, though often forgotten, remains a public health problem in India. Typhoid conjugate vaccines, produced by multiple Indian manufacturers, and recommended for use in high burden settings, ensure that the tools to tackle typhoid are an immediately available solution to this public health problem.


Subject(s)
COVID-19 , Typhoid Fever , Typhoid-Paratyphoid Vaccines , Humans , India/epidemiology , Pandemics , SARS-CoV-2 , Typhoid Fever/epidemiology , Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines/immunology , Vaccines, Conjugate/immunology
12.
Vaccine ; 40(1): 59-66, 2022 01 03.
Article in English | MEDLINE | ID: covidwho-1565666

ABSTRACT

BACKGROUND: Meningococcal serogroup C (MenC) vaccination was introduced for 14-month-olds in the Netherlands in 2002, alongside a mass campaign for 1-18 year-olds. Due to an outbreak of serogroup W disease, MenC vaccination was replaced for MenACWY vaccination in 2018, next to introduction of a booster at 14 years of age and a catch-up campaign for 14-18 year-olds. We assessed meningococcal ACWY antibodies across the Dutch population in 2016/17 and 2020. METHODS: In a nationwide cross-sectional serosurvey in 2016/17, sera from participants aged 0-89 years (n = 6886) were tested for MenACWY-polysaccharide-specific (PS) serum IgG concentrations, and functional MenACWY antibody titers were determined in subsets. Moreover, longitudinal samples collected in 2020 (n = 1782) were measured for MenACWY-PS serum IgG concentrations. RESULTS: MenC antibody levels were low, except in recently vaccinated 14-23 month-olds and individuals who were vaccinated as teenagers in 2002, with seroprevalence of 59% and 20-46%, respectively. Meningococcal AWY antibody levels were overall low both in 2016/17 and in 2020. Naturally-acquired MenW immunity was limited in 2020 despite the recent serogroup W outbreak. CONCLUSIONS: This study demonstrates waning of MenC immunity 15 years after a mass campaign in the Netherlands. Furthermore, it highlights the lack of meningococcal AWY immunity across the population and underlines the importance of the recently introduced MenACWY (booster) vaccination.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis, Serogroup C , Adolescent , Antibodies, Bacterial , Cross-Sectional Studies , Humans , Immunization, Secondary , Meningococcal Infections/epidemiology , Meningococcal Infections/prevention & control , Netherlands/epidemiology , Seroepidemiologic Studies , Vaccines, Conjugate
13.
J Infect Dis ; 224(4): 643-647, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1545949

ABSTRACT

Influenza is associated with primary viral and secondary bacterial pneumonias; however, the dynamics of this relationship in populations with varied levels of pneumococcal vaccination remain unclear. We conducted nested matched case-control studies in 2 prospective cohorts of Nicaraguan children aged 2-14 years: 1 before pneumococcal conjugate vaccine introduction (2008-2010) and 1 following introduction and near universal adoption (2011-2018). The association between influenza and pneumonia was similar in both cohorts. Participants with influenza (across types/subtypes) had higher odds of developing pneumonia in the month following influenza infection. These findings underscore the importance of considering influenza in interventions to reduce global pneumonia burden.


Subject(s)
Influenza, Human , Pneumococcal Infections , Pneumococcal Vaccines/administration & dosage , Case-Control Studies , Child , Child, Preschool , Humans , Infant , Influenza, Human/epidemiology , Nicaragua , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumonia, Pneumococcal/epidemiology , Pneumonia, Pneumococcal/prevention & control , Prospective Studies , Vaccines, Conjugate
14.
Expert Rev Vaccines ; 20(10): 1311-1325, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1486404

ABSTRACT

INTRODUCTION: The burden of pneumococcal disease in older UK adults remains substantial. Higher valency pneumococcal conjugate vaccines (PCVs) are currently in development with adult formulations for two of these anticipated to become available in 2022. This article collates and reviews relevant candidate data now available that may be used to support cost effectiveness assessments of vaccinating immunocompetent UK adults aged ≥65-years with PCVs. AREAS COVERED: This article uses published data from surveillance systems, randomized controlled trials and observational studies. It focuses on local data from the UK but where these are either limited or not available relevant global data are considered. EXPERT OPINION: The body of relevant data now available suggests the UK is well placed to assess the cost effectiveness of vaccinating immunocompetent ≥65-year olds with new generation higher valency PCVs. Recent contemporary data provide important new and robust insights into the epidemiology of pneumococcal disease in older UK adults and help to address much of the uncertainty and data gaps associated with previous analyses. Using these data to make informed decisions about use of new higher valency PCVs for routine use in older adults will be important for public health in the UK.


Subject(s)
Pneumococcal Infections , Pneumococcal Vaccines , Aged , Humans , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Uncertainty , United Kingdom/epidemiology , Vaccination , Vaccines, Conjugate
15.
Vaccine ; 39(42): 6189-6194, 2021 10 08.
Article in English | MEDLINE | ID: covidwho-1414779

ABSTRACT

BACKGROUND: Pneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population's vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage. METHODS: Vaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed. RESULTS: The total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020. CONCLUSIONS: Despite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.


Subject(s)
Pneumococcal Infections , Vaccination Coverage , Child , Child, Preschool , China , Humans , Infant , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , Vaccination , Vaccines, Conjugate
16.
MMWR Morb Mortal Wkly Rep ; 70(35): 1183-1190, 2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1395455

ABSTRACT

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) vaccines. Catch-up vaccination is recommended for hepatitis B (HepB); hepatitis A (HepA); measles, mumps, and rubella (MMR); and varicella (VAR) vaccines for adolescents whose childhood vaccinations are not current. Adolescents are also recommended to receive a booster dose of MenACWY vaccine at age 16 years, and shared clinical decision-making is recommended for the serogroup B meningococcal vaccine (MenB) for persons aged 16-23 years (1). To estimate coverage with recommended vaccines, CDC analyzed data from the 2020 National Immunization Survey-Teen (NIS-Teen) for 20,163 adolescents aged 13-17 years.* Coverage with ≥1 dose of HPV vaccine increased from 71.5% in 2019 to 75.1% in 2020. The percentage of adolescents who were up to date† with HPV vaccination (HPV UTD) increased from 54.2% in 2019 to 58.6% in 2020. Coverage with ≥1 dose of Tdap, ≥1 dose (and among adolescents aged 17 years, ≥2 doses) of MenACWY remained similar to coverage in 2019 (90.1%, 89.3%, and 54.4% respectively). Coverage increased for ≥2 doses of HepA among adolescents aged 13-17 years and ≥1 dose of MenB among adolescents aged 17 years. Adolescents living below the federal poverty level§ had higher HPV vaccination coverage than adolescents living at or above the poverty level. Adolescents living outside a metropolitan statistical area (MSA)¶ had lower coverage with ≥1 MenACWY and ≥1 HPV dose, and a lower proportion being HPV UTD than adolescents in MSA principal cities. In 2020, the COVID-19 pandemic disrupted routine immunization services. Results from the 2020 NIS-Teen reflect adolescent vaccination coverage before the COVID-19 pandemic. The 2020 NIS-Teen data could be used to assess the impact of the COVID-19 pandemic on catch-up vaccination but not on routine adolescent vaccination because adolescents included in the survey were aged ≥13 years, past the age when most routine adolescent vaccines are recommended, and most vaccinations occurred before March 2020. Continued efforts to reach adolescents whose routine medical care has been affected by the COVID-19 pandemic are necessary to protect persons and communities from vaccine-preventable diseases and outbreaks.


Subject(s)
Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage , Meningococcal Vaccines/administration & dosage , Papillomavirus Vaccines/administration & dosage , Vaccination Coverage/statistics & numerical data , Adolescent , Advisory Committees , COVID-19/epidemiology , Centers for Disease Control and Prevention, U.S. , Female , Health Care Surveys , Humans , Immunization Schedule , Male , Practice Guidelines as Topic , Socioeconomic Factors , United States/epidemiology , Vaccines, Conjugate/administration & dosage
17.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Article in English | MEDLINE | ID: covidwho-1387607

ABSTRACT

The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam2Cys-SK4 or Pam3Cys-SK4 These were produced by chemical synthesis using a peptide ligation strategy. The synthetic self-adjuvanting vaccines generated powerful local CD4+ T cell responses against ESAT6 and provided significant protection in the lungs from virulent M. tuberculosis aerosol challenge when administered to the pulmonary mucosa of mice. The flexible synthetic platform we describe, which allows incorporation of adjuvants to multiantigenic vaccines, represents a general approach that can be applied to rapidly assess vaccination strategies in preclinical models for a range of diseases, including against novel pandemic pathogens such as SARS-CoV-2.


Subject(s)
Mycobacterium tuberculosis/immunology , Tuberculosis Vaccines/pharmacology , Tuberculosis/immunology , Tuberculosis/prevention & control , Vaccines, Conjugate/pharmacology , Adjuvants, Immunologic/pharmacology , Animals , Antigens, Bacterial/immunology , BCG Vaccine/immunology , BCG Vaccine/pharmacology , Bacterial Proteins , CD4-Positive T-Lymphocytes/immunology , COVID-19/prevention & control , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , SARS-CoV-2/immunology , Toll-Like Receptor 2/immunology , Tuberculosis Vaccines/immunology , Vaccines, Conjugate/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/pharmacology
18.
ACS Chem Biol ; 16(7): 1223-1233, 2021 07 16.
Article in English | MEDLINE | ID: covidwho-1294432

ABSTRACT

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to elicit neutralizing antibodies to block viral sites binding to the host's cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.


Subject(s)
Antibodies, Neutralizing/immunology , Antibody Formation/immunology , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , SARS-CoV-2/immunology , Tetanus Toxoid/chemistry , Vaccines, Conjugate/administration & dosage , Animals , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Vaccination , Vaccines, Conjugate/immunology
19.
Vaccine ; 39(31): 4278-4282, 2021 07 13.
Article in English | MEDLINE | ID: covidwho-1275753

ABSTRACT

BACKGROUND: The COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years. METHODS: A Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged <5 years; absolute decreases from 10 to 50% for 1-2 years duration were examined, assuming no catch-up vaccination and that decreased vaccination led to proportionate increases in PCV13 serotype pneumococcal disease in children and seniors. Integrating pediatric model output into a second Markov model examining 65-year-olds, we estimated the cost effectiveness of older adult pneumococcal vaccination strategies while accounting for potential epidemiologic changes from decreased pediatric vaccination. RESULTS: One year of 10-50% absolute decreases in PCV13 use in <5-year-olds increased pneumococcal disease by an estimated 4-19% in seniors; 2 years of decreased use increased senior rates by 8-38%. In seniors, a >53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors. CONCLUSION: COVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable.


Subject(s)
COVID-19 , Pneumococcal Infections , Aged , Child , Child, Preschool , Cost-Benefit Analysis , Humans , Pandemics , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines , SARS-CoV-2 , Vaccination , Vaccines, Conjugate
20.
Vaccine ; 39(17): 2475-2478, 2021 04 22.
Article in English | MEDLINE | ID: covidwho-1265888

ABSTRACT

The first safe and effective vaccine for the prevention of invasive meningococcal disease was created fifty years ago. The vaccine employed a novel platform, polysaccharide capsular antigen, based on the discovery that anticapsular antibody conferred protective immunity in humans. As with most new paradigms in vaccinology, it derived from important basic research from other scientific disciplines over the preceding years. The success of the first monovalent polysaccharide vaccine in nearly eliminating invasive meningococcal disease in military settings led to accelerated advances in polysaccharide vaccine development against other serogroups of meningococcus and other encapsulated pathogens. As gaps in vaccine efficacy arose over the past half-century, new vaccine technologies and approaches were developed to address the challenges. Several of these, including conjugate vaccines and "reverse vaccinology" led to other novel, successful vaccines that have had a significant, favorable global impact on invasive meningococcal disease. The history of meningococcal vaccine discovery may provide insights into the future of vaccine efforts against other infectious threats.


Subject(s)
Meningococcal Infections , Meningococcal Vaccines , Neisseria meningitidis , Humans , Meningococcal Infections/prevention & control , Vaccines, Conjugate
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