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•Nationwide retrospective cohort study of Danish children aged 15months to 4years.•Comparison of the live MMR+the inactivated DTaP-IPV-Hib vaccine vs MMR alone.•27% higher rate of admissions for lower respiratory infections for MMR+DTaP-IPV-Hib.•No significant association with admissions for other types of infections.•Adjustment for a long range of potential confounders including exact age. In Denmark, live measles, mumps, and rubella vaccine (MMR) is associated with a reduced risk of infectious disease admissions, particularly for lower respiratory tract infections. In low-income countries, simultaneous vaccination (i.e. vaccination at the same visit) with live and inactivated vaccines may increase child mortality compared with the live vaccine alone. We examined the hypothesis that simultaneous administration of MMR and the inactivated DTaP-IPV-Hib vaccine compared with MMR alone is associated with higher incidence of infectious disease admissions. Nationwide, retrospective, register based cohort study of 520,859 children born in Denmark 1997–2006, who were followed from 15months to 4years of age. Incidence rate ratios (IRRs) of hospital admissions were estimated by Cox regression and adjusted for background factors including exact age. By 2years of age, 4965 children had simultaneous MMR and DTaP-IPV-Hib as their most recent vaccination. Compared with MMR alone, simultaneous administration was associated with a higher rate of lower respiratory tract infections (adjusted incidence rate ratio (IRR), 1.27; 95% confidence interval (CI), 1.13–1.42). There was no effect on other infections. Overall, simultaneous administration was associated with a 7% (95% CI, 0–15%) increase in infectious disease admissions. Simultaneous administration of MMR and DTaP-IPV-Hib compared with MMR alone may increase the rate of hospital admissions related to lower respiratory tract infections. These findings require replication in other high-income settings.

Yersinia pestis , the causative agent of plague, is a Tier-1 select agent and a reemerging human pathogen. A 2017 outbreak in Madagascar with >75% of cases being pneumonic and 8.6% causalities emphasized the importance of the disease. Mice immunized with a combination of an adenovirus vector (Ad5-YFV) and live-attenuated (LMA)-based vaccines were evaluated for protective efficacy against pneumonic plague. While the Ad5-YFV vaccine harbors a fusion cassette of three genes encoding YscF, F1, and LcrV, LMA represents a mutant of parental Yersinia pestis CO92 deleted for genes encoding Lpp, MsbB, and Ail. Ad5-YFV and LMA were either administered simultaneously (1-dose regimen) or 21 days apart in various orders and route of administration combinations (2-dose regimen). The 2-dose regimen induced robust immune responses to provide full protection to animals against parental CO92 and its isogenic F1 deletion mutant (CAF − ) challenges during both short- and long-term studies. Mice intranasally (i.n.) immunized with Ad5-YFV first followed by LMA (i.n. or intramuscularly [i.m.]) had higher T- and B-cell proliferative responses and LcrV antibody titers than those in mice vaccinated with LMA (i.n. or i.m.) first ahead of Ad5-YFV (i.n.) during the long-term study. Specifically, the needle- and adjuvant-free vaccine combination (i.n.) is ideal for use in plague regions of endemicity. Conversely, with a 1-dose regimen, mice vaccinated with Ad5-YFV i.n. and LMA by the i.m. route provided complete protection to animals against CO92 and its CAF − mutant challenges and elicited Th1/Th2, as well as Th17 responses, making it suitable for emergency vaccination during a plague outbreak or bioterrorist attack. This is a first study in which a viral vector-based and live-attenuated vaccines were effectively used in combination, representing adjuvant- and/or needle-free immunization, with each vaccine triggering a distinct cellular immune response. IMPORTANCE Yersinia pestis , the causative agent of plague, is a Tier-1 select agent and a reemerging human pathogen. A 2017 outbreak in Madagascar with >75% of cases being pneumonic and 8.6% causalities emphasized the importance of the disease. The World Health Organization has indicated an urgent need to develop new-generation subunit and live-attenuated plague vaccines. We have developed a subunit vaccine, including three components (YscF, F1, and LcrV) using an adenovirus platform (Ad5-YFV). In addition, we have deleted virulence genes of Y. pestis (e.g., lpp , msbB , and ail ) to develop a live-attenuated vaccine (LMA). Both of these vaccines generated robust humoral and cellular immunity and were highly efficacious in several animal models. We hypothesized the use of a heterologous prime-boost strategy or administrating both vaccines simultaneously could provide an adjuvant- and/or a needle-free vaccine(s) that has attributes of both vaccines for use in regions of endemicity and during an emergency situation.

This double-blind randomized controlled study of 52 elderly patients with diabetes assessed cell-mediated immunity and safety of BIKEN varicella-zoster vaccine (BVZV). Cellular and humoral responses to VZV at 3 months after BVZV and 23-valent polysaccharide pneumococcal vaccine (PPSV23) vaccination elicited poor results. Post-hoc analyses assessed the effects of immunogenicity of PPSV23. Using standardized enzyme-linked immunosorbent assay, pneumococcal 6B and 23F serotype-specific immunoglobulin G (IgG)-binding antibody concentrations were measured in stored samples retrospectively before administration and 3 months after. Responders increased more than twofold in at least one serotype-specific IgG. The geometric mean concentration ratio (GMCR) of serum anti-pneumococcal 6B IgG was 1.76 (95%C.I.: 0.58, 5.34) in patients receiving concurrent PPSV23 and BVZV, compared to 2.39 (95%C.I.: 0.53, 10.76) in patients receiving PPSV23 and placebo (P = .055). The GMCR of serum anti-pneumococcal 23F IgG was 2.54 (95%C.I.: 0.57, 11.43) in PPSV23/BVZV vaccinees compared to 3.34 (95%C.I.: 0.84, 12.92) in PPSV23/placebo vaccinees (P = .424). Responder rates, those who developed antibodies to either/both serotypes, were 68% in the BVZV group and 85% in the placebo group (P = .007). Results suggest that concurrent administration of BVZV influenced humoral responses to PPSV23 in elderly subjects with diabetes.

In this paper, a method of simultaneous immunizing BALB/c mice with staphylococcal enterotoxin (SE) A and B (SEA and SEB) to prepare a monoclonal antibody (3F2) for detecting both of SEA and SEB was developed. The results showed that antibody 3F2 had high titers against both SEA and SEB by enzyme-linked immunosorbent assay (ELISA). The sensitivities of 3F2 to SEA and SEB detected by ELISA were 133.2 and 82.5 ng/mL, respectively, and the detection limits for the two enterotoxins were about 1 ng/mL. The antibody 3F2 had high specificities and affinities to both SEA and SEB, and had no cross-reaction with SEC 1 , bovine serum albumin, and ovalbumin. SEs-free skimmed milk samples were spiked with different concentrations of SEA, SEB, or both of them, respectively. Average recoveries of SEA and SEB from the spiked samples were all nearly between 82% and 104%. The result suggested that one cell fusion with simultaneous immunization by multiple antigen to prepare monoclonal antibody against them was possible, simple, and economic. The monoclonal antibody could be used in simultaneous detecting multifarious SEs.

•MOSVs were common, with three out of five children experiencing at least one missed opportunity.•Once MOSVs occurred, children in rural areas had their missed opportunities corrected more frequently compared to their urban counterparts.•All eighteen vaccine doses for which the study cohort was eligible, could have achieved higher coverage if MOSVs had been avoided with possible gains ranging from less than one to about eleven percentage points with full basic vaccination gaining up to thirteen percentage points.•The unequal distribution of MOSV correction between urban and rural areas did not contribute significantly to the overall urban–rural coverage inequity, but it did contribute 95% to coverage inequity among children who experienced MOSVs before the survey. Identifying actionable targets is crucial to improve overall and equity in vaccination coverage, and in line with the global Immunization Agenda 2030. Therefore, this study seeks to assess the prevalence of missed opportunities for simultaneous vaccination (MOSVs) and their impact on vaccination coverage and urban–rural inequity in The Gambia. We used data of children aged 12–23 months from The Gambia 2019/2020 demographic and health survey (weighted n = 1355) with seen vaccination cards. We analyzed: the frequency of MOSVs; percentage point coverage reduction attributable to MOSVs for 18 vaccine doses and full basic vaccination; and MOSVs' contribution to urban–rural coverage inequity through Blinder-Oaxaca decomposition. Sixty percent of children experienced MOSVs, in both urban and rural areas, but urban MOSVs were more seldom corrected (35.9 % vs 45.3 %). All eighteen vaccine doses assessed could have achieved between one to eleven percentage points higher coverage if MOSVs had been avoided, with full basic vaccination gaining even more. While MOSV correction did not impact overall urban–rural coverage inequity, it did exacerbate (explained coefficient = -0.1007; P = 0.002) inequities among children who experienced MOSVs, explaining 95 % of the observed difference. Our study highlights the prevalence and negative impact of MOSVs on overall vaccination coverage. Although MOSVs did not contribute significantly to the total urban–rural inequity in coverage, they have detrimental effects on vaccination coverage and urban–rural inequity among children who had experienced MOSVs. Addressing MOSVs, can enhance coverage and reduce the risk of under-vaccination, aligning with global initiatives.

Safety data on simultaneous vaccination (SV) with primary series monovalent COVID-19 vaccines and other vaccines are limited. We describe SV with primary series COVID-19 vaccines and assess 23 pre-specified health outcomes following SV among persons aged ≥5 years in the Vaccine Safety Datalink (VSD). We utilized VSD’s COVID-19 vaccine surveillance data from December 11, 2020-May 21, 2022. Analyses assessed frequency of SV. Rate ratios (RRs) were estimated by Poisson regression when the number of outcomes was ≥5 across both doses, comparing outcome rates between COVID-19 vaccinees receiving SV and COVID-19 vaccinees receiving no SV in the 1–21 days following COVID-19 vaccine dose 1 and 1–42 days following dose 2 by SV type received (“All SV”, “Influenza SV”, “Non-influenza SV”). SV with COVID-19 vaccines was not common practice (dose 1: 0.7 % of 8,455,037 persons, dose 2: 0.3 % of 7,787,013 persons). The most frequent simultaneous vaccines were influenza, HPV, Tdap, and meningococcal. Outcomes following SV with COVID-19 vaccines were rare (total of 56 outcomes observed after dose 1 and dose 2). Overall rate of outcomes among COVID-19 vaccinees who received SV was not statistically significantly different than the rate among those who did not receive SV (6.5 vs. 6.8 per 10,000 persons). Statistically significant elevated RRs were observed for appendicitis (2.09; 95 % CI, 1.06–4.13) and convulsions/seizures (2.78; 95 % CI, 1.10–7.06) in the “All SV” group following dose 1, and for Bell’s palsy (2.82; 95 % CI, 1.14–6.97) in the “Influenza SV” group following dose 2. Combined pre-specified health outcomes observed among persons who received SV with COVID-19 vaccine were rare and not statistically significantly different compared to persons who did not receive SV with COVID-19 vaccine. Statistically significant adjusted rate ratios were observed for some individual outcomes, but the number of outcomes was small and there was no adjustment for multiple testing.

•Missed opportunities for simultaneous administration of the fourth dose of DTaP.•Prevalence rates vary 5.7–9.0% in years, and 3.3–22.9% in domains.•Timeliness of the first 3 doses of DTaP are significant and modifiable risk factors.•Adjusted prevalence ratios are 1.7, 1.6, 3.2 respectively and all P-value<0.01. Simultaneous administration of all age-appropriate doses of vaccines is an effective strategy for raising vaccination coverage. Vaccination coverage for ≥4 dose of DTaP (diphtheria, tetanus toxoids, and acellular pertussis vaccine) among children 19–35months in the United States has not reached the Healthy People 2020 target of 90%. Risk factors for missed opportunities for simultaneous administration of the fourth dose of DTaP have not been investigated. A missed opportunity for simultaneous administration of the fourth dose of DTaP is defined as the failure to administer an age-eligible fourth dose of DTaP, and during the same age-eligible period for the fourth dose of DTaP other recommended and age-appropriate doses of vaccines are given to children. This study used 2001–2014 National Immunization Survey data to describe the trend in missed opportunities for simultaneous administration of the fourth dose of DTaP from 2001 through 2014, assess the prevalence of children who missed opportunities for simultaneous administration of the fourth dose of DTaP by selected factors, and recognize significant risk factors for missed opportunities for simultaneous administration of the fourth dose of DTaP. From 2001 to 2014, the prevalence of missed opportunities for simultaneous administration of the fourth dose of DTaP among children 19–35months in the United States ranged from 5.7% to 9.0%; across 13 factors considered, the prevalence of missed opportunities varied from 3.3% to 22.9%. Children who were late in receiving the first to third dose of DTaP had significantly higher prevalence of missed opportunities for simultaneous administration of the fourth dose of DTaP than children who received these doses on-time, with adjusted prevalence ratios for late vs. on-time of 1.7, 1.6, and 3.2, and all P-value<0.01. Improving on-time vaccination of the third dose of DTaP could substantially reduce missed opportunities for simultaneous administration of the fourth dose of DTaP.

Background In China, enterovirus 71 (EV71) is the major etiological agents of hand foot mouth disease that poses severe risks to children’s health. Since 2015, three inactivated EV71 vaccines have been approved for use. Previous studies indicated the high willingness of EV71 vaccination in eastern China. However, few studies have assessed coverage and utilization patterns of EV71 vaccine in China. Methods Children born during 2012–2018 were sampled and their records were abstracted from Ningbo childhood immunization information management system. Descriptive statistics characterized the study population and assessed coverage and timeliness for EV71 vaccination. Simultaneous administration patterns as well as type of EV71 vaccine used were also evaluated. Bivariate and multivariable analysis was used to examine the relationship of socio-demographic characteristics with vaccination coverage and timeliness. Results Of 716,178 children living in Ningbo. One hundred seventy-two thousand two hundred thirty-six received EV71 vaccine with a coverage rate of 24.05% and only 8.61% received vaccination timely. 21.97% of children received the complete two dose EV71 series but only 6.49% completed timely. Vaccination coverage and timeliness increased significantly from 2012 birth cohort to 2018 birth cohort. Relatively higher coverage and timeliness were observed in resident children, Inner districts, high socioeconomic areas and large-scaled immunization clinics. Of 329,569 doses of EV71 vaccine, only 5853(1.78%) doses were administered at the same day as other vaccines. Conclusions There is a need for increasing EV71 vaccination coverage and timeliness as well as eliminating disparities among different populations. Our study highlights the importance of simultaneous administration to increasing coverage and timeliness of EV71 vaccination.

The U.S. Food and Drug Administration authorized use of mRNA COVID-19 bivalent booster vaccines on August 31, 2022. Currently, CDC’s clinical guidance states that COVID-19 and other vaccines may be administered simultaneously. At time of authorization and recommendations, limited data existed describing simultaneous administration of COVID-19 bivalent booster and other vaccines. We describe simultaneous influenza and mRNA COVID-19 bivalent booster vaccine administration between August 31–December 31, 2022, among persons aged ≥6 months in the Vaccine Safety Datalink (VSD) by COVID-19 bivalent booster vaccine type, influenza vaccine type, age group, sex, and race and ethnicity. Of 2,301,876 persons who received a COVID-19 bivalent booster vaccine, 737,992 (32.1%) received simultaneous influenza vaccine, majority were female (53.1%), aged ≥18 years (91.4%), and non-Hispanic White (55.7%). These findings can inform future VSD studies on simultaneous influenza and COVID-19 bivalent booster vaccine safety and coverage, which may have implications for immunization service delivery.

This case–control study investigated immune thrombocytopenic purpura (ITP) risk following live, inactivated, and simultaneous vaccination, with a focus on infants aged < 2 years. We matched case patients with ITP to one or two control patients with other diseases by institution, hospital visit timing, sex, and age. We calculated McNemar’s pairwise odds ratios (ORs [95% confidence interval]) with 114 case–control pairs. The case group had 27 (44%) males and 22 (35%) infants, and the control group included 49 (43%) males and 42 (37%) infants. For all age groups, the McNemar’s OR for ITP occurrence was 1.80 (0.54–6.84, p = 0.64) for all vaccines. Among infants, these were 1.50 (0.17–18.0, p = 0.50) for all vaccines, 2.00 (0.29–22.1, p = 0.67) for live vaccines, and 1.00 (0.01–78.5, p = 0.50) for inactivated vaccines. Sex-adjusted common ORs for simultaneous vaccination were 1.52 (0.45–5.21, p = 0.71) for all vaccines, 1.83 (0.44–7.59, p = 0.40) for inactivated vaccines only, and 1.36 (0.29–6.30, p = 0.69) for mixed live and inactivated vaccines. In infants, these were 1.95 (0.44–8.72, p = 0.38), 1.41 (0.29–6.94, p = 0.67) and 2.85 (0.43–18.9, p = 0.28), respectively. These limited data suggest no significant ITP risk following vaccinations or simultaneous vaccination in any age group, including infants.