Safety Of PCV13 Research Articles

How effective is 13-valent pneumococcal conjugate vaccine (PCV13) combined with 23-valent pneumococcal polysaccharide vaccine (PPSV23)?

The bacterium Streptococcus pneumoniae remains a major causeof morbidity and mortality worldwide. Currently, the 2 leading vaccines targeted against it are: 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13). It was only very recently, starting 22 November 2019, that the Advisory Committee on Immunisation Practices (ACIP) no longer recommends routine administration of PCV13 for all adults aged 65 and above. As such, this systematic review aims to investigate how the use of PCV13 combined with PPSV23 compares to using PPSV23 alone in older adults. Relevant research papers were chosen through an electronic searchin PubMed. A set of selection criteria was then applied to ensure that the papers aligned with the objectives of this paper. The majority of the studies included in this paper demonstrated that in adults aged 50 years and above, PCV13 had the ability to generate a strong immune response in adults, even more so than PPSV23 for all of the twelve serotypes common to both vaccines. The safety of PCV13 was also demonstrated in the studies as no PCV13-related serious adverse events (SAEs) had surfaced. Only one study included in this systematic review opposed the trend.While the evidence for both PCV13’s and PPSV23’s ability to generate an immune response have been persuasive, more research that focuses on the clinical endpoint in older adults, as well as the incidence of pneumococcal infections in the population, could be done to fully address the main question of this paper.

Kawasaki Disease Following the 13-valent Pneumococcal Conjugate Vaccine and Rotavirus Vaccines.

Temporal associations between Kawasaki disease (KD) and childhood vaccines have been reported. Limited data on KD following 13-valent pneumococcal conjugate (PCV13) and rotavirus vaccines are available. We conducted a self-controlled risk interval study using Vaccine Safety Datalink electronic health record data to investigate the risk of KD following PCV13 and rotavirus vaccines in children <2 years of age who were born from 2006 to 2017. All hospitalized KD cases identified by International Classification of Diseases diagnosis codes that fell within predefined risk (days 1-28 postvaccination) and control (days 29-56 for doses 1 and 2, and days 43-70 for doses 3 and 4) intervals were confirmed by manual chart review. During the study period, 655 cases of KD were identified by International Classification of Diseases codes. Of these, 97 chart-confirmed cases were within risk or control intervals. In analyses, the age-adjusted relative risk for KD following any dose of PCV13 was 0.75 (95% confidence interval, 0.47-1.21). Similarly, the age-adjusted relative risk for KD following any dose of rotavirus vaccine was 0.66 (95% CI, 0.40-1.09). Overall, there was no evidence of an elevated risk of KD following PCV13 or rotavirus vaccines by dose. In addition, no statistically significant temporal clustering of KD cases was identified during days 1 to 70 postvaccination. PCV13 and rotavirus vaccination were not associated with an increased risk of KD in children <2 years of age. Our findings provide additional evidence for the overall safety of PCV13 and rotavirus vaccines.

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naïve and previously immunized adult patients with severe chronic kidney disease

Individuals with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although the 13-valent pneumococcal conjugate vaccine (PCV13) has been found to have higher immunogenicity compared to PPV23 in adults with some immunocompromising conditions, previous PPV23 immunization may decrease the immunogenicity of PCV13. We assessed immunogenicity and safety of PCV13 in 74 PPV23-naïve and 58 previously PPV23-immunized (>1 year ago) patients with severe (stage 4–5) CKD. Serum IgG, IgM, and IgA specific to seven serotypes, i.e. 3, 6B, 9V, 14, 19A, 19F, 23F were quantified pre- and 4 weeks and one year post-immunization.Baseline concentrations for most serotype-specific IgG and IgM, and serotype 3-specific IgA were higher in previously PPV23-immunized compared to PPV23-naïve patients. Immunization with PCV13 significantly increased almost all serotype-specific IgG, all IgA and some IgM; an increase in some serotype-specific IgG and IgM lasted for one year. Fold increases in antibody concentrations and the proportion of individuals with >2-fold increase post-immunization were generally larger in PPV23-naïve than previously immunized patients for most serotype-specific IgG and some IgA. The data show that in patients with CKD who received previous PPV23 immunization over one year ago, the antibody response to PCV13 was inferior compared to pneumococcal vaccine naïve study participants. In both groups, the lowest response to PCV13 was found for serotype 3. Patients of Indigenous ethnic background demonstrated a superior immune response to PCV13 compared to the non-Indigenous counterpart that could partially be related to Indigenous study participants' younger age. Although we found that previous PPV23 immunization could contribute to the more frequent occurrence of systemic adverse events post PCV13 immunization, those did not exceed the mild to moderate range.

Efficacy and Safety of the Pneumococcal Conjugate-13 Valent Vaccine in Adults.

Invasive pneumococcal disease and pneumococcal pneumonia cause substantial morbidity and mortality in the elderly. This review focuses on the immunogenicity, safety, efficacy and effectiveness data on the use of the 13-valent conjugate pneumococcal vaccine (PCV13) in adults. A MEDLINE literature search was performed from January 1946 to December 2017. Additional references were identified from a review of literature citations. All English-language randomized trials, observational studies and meta-analyses assessing the immunogenicity, efficacy, effectiveness and safety of PCV13 in adults were evaluated. Six randomized controlled studies evaluated immunogenicity and safety of PCV13 in adults and showed that the conjugated vaccine elicited a greater immune response to the majority of the 13 serotypes compared to the 23-valent polysaccharide pneumococcal vaccine (PPV23). Administering PCV13 prior to PPV23 elicits greater immune responses and multiple doses of PCV13 demonstrated modest advantage. PCV13 titers declined after a year but remained above baseline. A randomized clinical trial (CAPiTA) showed that PCV13 was effective in preventing community-acquired pneumonia (CAP) and vaccine-type invasive pneumococcal disease, but not any cause pneumonia. Safety data shows PCV13 elicits minor local reactions, such as pain at the injection site. Major side effects that were commonly reported included muscle fatigue and headache. Both local and systemic adverse events were comparable to PPV23. While PCV13 has a well-established immunogenicity and safety profile in adults, there is sparse data on sequential or multiple dosing, efficacy and effectiveness in adults. As there are few countries who have adopted PCV13 for routine adult immunization, there is a need to evaluate the effectiveness of PCV13 in a real-world setting.

Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Solid Organ Transplant (SOT) Candidates and Recipients.

Purpose:The United States Advisory Committee on Immunization Practices recommends that PCV13 be given in addition to 23-valent pneumococcal polysaccharide vaccine to immunocompromised adults, such as chronic renal failure and SOT. However, data regarding this is sparse. The present study aimed to assess the immunogenicity and safety of PCV13 in SOT candidates and recipients. Methods: Consecutive patients receiving pre-SOT evaluation and SOT receipts with stable clinical conditions 6 months post transplant were enrolled. Symptoms developed within 7 days after one dose PCV13 and anti-capsular antibody responses against 4 serotypes (6B, 14, 19F and 23F) at baseline and 1 month following vaccination were recorded. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at 1 month compared with the baseline. Results:From 2013/10/1 to 2013/12/30, a total of 21 study patients were enrolled. PCV13 was given to 19 (90.5%) SOT candidates and 2 (9.5%) heart recipients; the two heart recipients received PCV13 60 months and 1320 months after transplantation. Two SOT candidates received liver transplantation after PCV13 administration; the durations from PCV13 vaccination to transplantation were 44 and 23 days, respectively. Only 2 (9.5%) study patients felt pain at PCV13 injection site, and 1 (4.8%) had fever after PCV13 administration; all symptoms subsided spontaneously. Of 19 study patients receiving PCV13 before transplantation, 13 (68.4%) were liver transplant candidates, 5 (26.3%) were heart transplant candidates, and 1 (5.3%) was lung transplant candidate. The geometric mean titer of baseline antibody titer for 6B, 14, 19F, and 23F of the 21 study patients were 2719.04 ng/mL, 15259.20 ng/mL, 3828.42 ng/mL, and 1897.98 ng/mL, respectively. Thirteen (61.9%) patients had 1-month follow-up. At 1 month, 58.3%, 58.3%, 70.0%, and 75.0% of the study patients had significant antibody responses against 6B, 14, 19F and 23F, respectively. None of them developed pneumonia at the time of the abstract drafting. Conclusion: The use of PCV13 appeared safe and immunogenic in SOT candidates and recipients during a short-term follow-up.

Immunogenicity and Safety of a 13-valent Pneumococcal Conjugate Vaccine in Healthy Infants in Japan

A 13-valent pneumococcal conjugate vaccine (PCV13) containing 6 additional serotypes not included in the 7-valent PCV has been developed to broaden protection against Streptococcus pneumoniae, which is responsible for over 500,000 deaths annually worldwide in children <5 years of age. This study in Japanese infants evaluated the immunogenicity and safety of PCV13 given subcutaneously, the standard route for infant vaccination in Japan. This phase 3, single-arm, open-label study was conducted at 25 sites. Subjects received PCV13 as a 3-dose infant series and a toddler dose. Parents/legal guardians recorded local reactions and systemic events after each vaccination. The proportion of subjects with serotype-specific antipneumococcal polysaccharide immunoglobulin (Ig)G antibody concentrations ≥0.35 µg/mL was calculated before and 1 month after the infant series and toddler dose. A total of 193 subjects enrolled. The proportion of subjects achieving pneumococcal IgG antibody concentrations ≥0.35 µg/mL was ≥97.2% for all 13 pneumococcal serotypes 1 month after the infant series and 98.9-100% after the toddler dose. IgG geometric mean concentrations were 2.57-14.69 µg/mL after the infant series and 2.06-16.33 µg/mL after the toddler dose. IgG geometric mean concentrations increased from pre- to posttoddler dose by ≥2.8-fold, demonstrating a booster effect. Local reactions and fever were generally mild or moderate in severity. PCV13 was immunogenic for all serotypes and had a favorable safety profile when administered subcutaneously to Japanese infants. PCV13 should offer broader serotype protection than 7-valent PCV in preventing pneumococcal disease in Japanese children.

13-Valent pneumococcal conjugate vaccine (PCV13) in children partially immunized with 7-valent pneumococcal conjugate vaccine (PCV7): A phase 3, open-label trial

BackgroundAs 13-valent pneumococcal conjugate vaccine (PCV13) is introduced, children who began vaccination with 7-valent pneumococcal conjugate vaccine (PCV7) may complete their vaccination with PCV13. This open-label phase 3 study evaluated immunogenicity and safety of PCV13 in Swedish infants and toddlers previously given 1 or 2 doses of PCV7 during infancy. MethodsHealthy infants previously given PCV7 at ages 3 months (group 1; n=118) or 3 and 5 months (group 2; n=116) received PCV13 at ages 5 (group 1) and 12 months (both groups). IgG responses were assessed 1 month after each PCV13 dose and before the 12-month dose. Local reactions and systemic events were collected for 7 days postvaccination. Other adverse events were also collected. ResultsPost-5-month dose, IgG geometric mean concentrations (GMCs) in group 1 were 1.56–4.70μg/ml for most PCV7 serotypes except 6B (0.40μg/ml) and 23F (0.57μg/ml) and 0.72–1.88μg/ml for most of the 6 additional serotypes, except 6A (0.28μg/ml). Post-12-month dose, IgG GMCs for the PCV7 serotypes were 2.93–9.63μg/ml (group 1) and 3.33–9.30μg/ml (group 2); and for the 6 additional serotypes, 1.85–14.65μg/ml (group 1) and 1.34–13.16μg/ml (group 2). GMCs increased by >4-fold in both groups from pre- to post-12-month dose. Proportions of subjects in group 1 with pneumococcal serotype-specific IgG concentrations ≥0.35μg/ml (WHO-designated postprimary reference antibody level) post-5-month dose were 92.2–99.1% for most PCV7 serotypes except 6B (53.0%) and 23F (62.6%) and 80.9–100.0% for most of the 6 additional serotypes except 6A (36.8%). Local reactions and fever were mostly mild or moderate. ConclusionsPCV13 was immunogenic and safe in infants and toddlers previously partially immunized with PCV7. Even a single dose in an infant or toddler induces an immune response to the 6 additional serotypes.

13-valent Pneumococcal Conjugate Vaccine Given With Meningococcal C–Tetanus Toxoid Conjugate and Other Routine Pediatric Vaccinations

As multiple vaccines are administered concomitantly during routine pediatric immunizations, it is important to ascertain the potential interference of any new vaccine on the immune response to the concomitantly administered vaccines. Immune responses to meningococcal serogroup C-tetanus toxoid conjugate vaccine (MnCC-TT) and the diphtheria and tetanus antigens in routine pediatric vaccines (diphtheria, tetanus, acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenza type b [DTaP-HBV-IPV/Hib] and DTaP-IPV+Hib) when given concomitantly with the 13-valent pneumococcal conjugate vaccine (PCV13) were compared with responses when given with PCV7. In addition, the immunogenicity and safety of PCV13 were assessed. Healthy infants were randomized to receive PCV13 or PCV7 (ages 2, 4, 6 and 15 months), concomitant with MnCC-TT (2, 4 and 15 months), DTaP-HBV-IPV/Hib (2, 4 and 6 months), and DTaP-IPV+Hib (15 months). Immune responses to MnCC-TT and to the diphtheria and tetanus antigens administered with PCV13 were noninferior to the responses observed when the vaccines were administered with PCV7; ≥96.6 (postinfant) and ≥99.4% (posttoddler) subjects achieved prespecified immune response levels to each antigen in each group. After the infant series, ≥93.0% of subjects receiving PCV13 achieved pneumococcal anticapsular immunoglobulin G concentrations ≥0.35 µg/mL for all serotypes except serotype 3 (86.2%), increasing to 98.1-100% for most serotypes (serotype 3: 93.6%) after the toddler dose. Local and systemic reactions were similar between groups. Immune responses to MnCC-TT, and other childhood vaccines (DTaP-HBV-IPV/Hib, DTaP-IPV+Hib) were noninferior when concomitantly administered with PCV13 compared with PCV7. PCV13 does not interfere with MnCC-TT. PCV13 is highly immunogenic with a favorable safety profile.

Review on the immunogenicity and safety of PCV-13 in infants and toddlers

Pneumococcal polysaccharide–protein conjugate vaccines (PCVs) generally protect against vaccine-serotype-specific pneumococcal disease. Additional serotypes included in the new 13-valent PCV (PCV-13) formulation and not in the first-generation 7-valent PCV (PCV-7) formulations are 1, 3, 5, 6A, 7F and 19A. Importantly, serotype 1 is associated with a high proportion and burden of pneumococcal disease in low-income countries, whilst serotype 19A emerged as the dominant disease-causing serotype following widespread PCV-7 immunization in the USA. In this article we present the available data on the immunogenicity and safety of PCV-13 in infants and children. Noninferiority studies indicate a similar immunogenicity profile between PCV-13 and PCV-7 recipients against most of the common serotypes. A favorable immunogenicity profile was also observed for at least five of the additional serotypes in PCV-13. An attenuated anamnestic response to serotype 3 was reported in five out of 14 studies. PCV-13 was demonstrated to have a similar acceptable safety profile to PCV-7 and no interference in immunogenicity of other concomitantly administered childhood vaccines was observed among PCV-13 recipients.