Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial

Abstract

It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4–6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, −10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4–6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2020–21 Influenza Season

“…Simultaneous administration of IIV4 and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to persons aged ≥65 years was associated with lower seroprotection rates to one influenza B antigen at 4-6 weeks postvaccination as compared with sequential administration 2 weeks apart; seroprotection was not significantly different between the two groups for any of the four influenza antigens at 6 months postvaccination (88). Reassuring safety profiles have been noted for simultaneous administration of IIVs with live attenuated zoster vaccine (83,84), PCV13 (85,86), PPSV23 (88,89), and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine among adults (87) and of Tdap among pregnant women (90). Although increased prevalence of injection site or systemic adverse reactions has been noted with concurrent administration in some of these studies, these symptoms have generally been reported to be mild or moderate.…”

“…In some studies, reduced responses have been noted to 13-valent pneumococcal conjugate vaccine (PCV13) ( 85 , 86 ), tetanus antigens ( 87 ), and pertussis antigens ( 87 ) when co-administered with IIV3 to adults; in most instances, the clinical significance of this is uncertain. Simultaneous administration of IIV4 and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to persons aged ≥65 years was associated with lower seroprotection rates to one influenza B antigen at 4–6 weeks postvaccination as compared with sequential administration 2 weeks apart; seroprotection was not significantly different between the two groups for any of the four influenza antigens at 6 months postvaccination ( 88 ). Reassuring safety profiles have been noted for simultaneous administration of IIVs with live attenuated zoster vaccine ( 83 , 84 ), PCV13 ( 85 , 86 ), PPSV23 ( 88 , 89 ), and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine among adults ( 87 ) and of Tdap among pregnant women ( 90 ).…”

<p>Strategies for Geriatric Pneumonia in Healthcare Facilities – How Effective is Combined Influenza and Pneumococcal Vaccination?</p>

“… 11 Moreover, the combination of a new quadrivalent influenza vaccine and 23-valent pneumococcal polysaccharide vaccine was suggested to have an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions for elderly Japanese people. 12 …”

Co-administration of vaccines: a focus on tetravalent Measles-Mumps-Rubella-Varicella (MMRV) and meningococcal C conjugate vaccines

“…9 Co-administration of different vaccines results to be immunogenic and well-tolerated as described in several papers. 15 - 17 To cite some examples, Nakashima et al 18 and Thompson et al 19 concluded that co-administration of the quadrivalent influenza vaccine and the 23-valent pneumococcal polysaccharide vaccine (PPV23) and with the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) respectively, is a safe and effective practice and does not lead to an increase in adverse reactions. 18 , 19 Several authors evaluated the safety and immunogenicity of the quadrivalent meningococcal conjugate vaccine (Men ACWY) co-administered with common childhood vaccines, confirming good tolerability, elevated immunogenicity, and safety.…”

“… 15 - 17 To cite some examples, Nakashima et al 18 and Thompson et al 19 concluded that co-administration of the quadrivalent influenza vaccine and the 23-valent pneumococcal polysaccharide vaccine (PPV23) and with the 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) respectively, is a safe and effective practice and does not lead to an increase in adverse reactions. 18 , 19 Several authors evaluated the safety and immunogenicity of the quadrivalent meningococcal conjugate vaccine (Men ACWY) co-administered with common childhood vaccines, confirming good tolerability, elevated immunogenicity, and safety. 20 – 24 Finally, with regard to the concomitant administration of meningococcal C conjugated vaccines (as tetravalent or monovalent vaccines) and MMRV, which will be further investigated in the course of this review, in recent studies performed by Durando et al 5 and Klein et al, 2 this co-administration appears to be well tolerated, without safety issues and with a good immune response for both vaccines.…”