Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases,solid organ transplantation or after bone-marrow transplantation – A systematic review of randomized trials,observational studies and case reports

BackgroundLive vaccines are generally contraindicated on immunosuppressive therapy due to safety concerns. However, data are limited to corroborate this practice.ObjectivesTo estimate the safety of live vaccinations in patients with immune-mediated inflammatory diseases (IMID) or solid organ transplantation (SOT) on immunosuppressive treatment and in patients after bone-marrow transplantation (BMT).Data SourcesA search was conducted in electronic databases (Cochrane, Pubmed, Embase) and additional literature was identified by targeted searches.Eligibility criteriaRandomized trials, observational studies and case reports.PopulationPatients with IMID or SOT on immunosuppressive treatment and BMT patients <2 years after transplantation.Intervention/vaccinations looked atLive vaccinations: mumps, measles, rubella (MMR), yellow fever (YF), varicella vaccine (VV), herpes zoster (HZ), oral typhoid, oral polio, rotavirus, Bacillus Calmette–Guérin (BCG), smallpox.Data extractionOne author performed the data extraction using predefined data fields. It was cross-checked by two other authors.Results7305 articles were identified and 64 articles were included: 40 on IMID, 16 on SOT and 8 on BMT patients. In most studies, the administration of live vaccines was safe. However, some serious vaccine-related adverse events occurred. 32 participants developed an infection with the vaccine strain; in most cases the infection was mild. However, in two patients fatal infections were reported: a patient with RA/SLE overlap who started MTX/dexamethasone treatment four days after the YFV developed a yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and died. The particular vaccine lot was found to be associated with a more than 20 times risk of YEL-AVD. One infant whose mother was under infliximab treatment during pregnancy received the BCG vaccine at the age of three months and developed disseminated BCG infection and died. An immunogenicity assessment was performed in 43 studies. In most cases the patients developed satisfactory seroprotection rates. In the IMID group, YFV and VV demonstrated high seroconversion rates. MTX and tumor necrosis factor inhibitory therapy appeared to reduce immune responses to VV and HZ vaccine, but not to MMR and YF-revaccination. Seroconversion in SOT and BMT patients showed mostly higher rates for rubella than for measles, mumps and varicella.LimitationsRisk of bias was high in the majority of studies since 39 of them were observational and 17 were case series/case reports. Only eight studies were randomized trials. BMT patient numbers included in this review were low.ConclusionsAlthough live vaccinations were safe and sufficiently immunogenic in most studies, some serious reactions and vaccine-related infections were reported in immunosuppressed IMID and SOT patients. Apart from mild vaccine-related infections MMR and VV vaccines were safe when administered less than two years after BMT.Implications of key findingsUntil further data are available, live vaccinations under most immunosuppressive treatments should only be administered after a careful risk benefit assessment of medications and dosages.FundingNone.     

MMR vaccination status of children exempted from school-entry immunization mandates

BackgroundChild immunizations are one of the most successful public health interventions of the past century. Still, parental vaccine hesitancy is widespread and increasing. One manifestation of this are rising rates of nonmedical or “personal beliefs” exemptions (PBEs) from school-entry immunization mandates. Exemptions have been shown to be associated with increased risk of disease outbreak, but the strength of this association depends critically on the true vaccination status of exempted children, which has not been assessed.ObjectiveTo estimate the true measles-mumps-rubella (MMR) vaccination status of children with PBEs.MethodsWe use administrative data collected by the California Department of Public Health in 2009 and imputation to estimate the MMR vaccination status of children with PBEs under varying scenarios.ResultsResults from 2009 surveillance data indicate MMR1/MMR2 coverage of 18–47% among children with PBEs at typical schools and 11–34% among children with PBEs at schools with high PBE rates. Imputation scenarios point to much higher coverage (64–92% for MMR1 and 25–58% for MMR2 at typical schools; 49–90% for MMR1 and 16–63% for MMR2 at high PBE schools) but still below levels needed to maintain herd immunity against measles.ConclusionsThese coverage estimates suggest that prior analyses of the relative risk of measles associated with vaccine refusal underestimate that risk by an order of magnitude of 2–10 times.     

Immunogenicity and safety of measles-mumps-rubella vaccine at two different potency levels administered to healthy children aged 12–15 months: A phase III,randomized, non-inferiority trial

BackgroundThe potency of live viral vaccines decreases over time. We compared the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT) formulations at two different potencies with that of the commercially-available MMR II formulation.MethodsIn this phase III observer-blind clinical study (NCT01681992), 4516 healthy children aged 12–15 months were randomized (1:1:1 ratio) to receive one dose of MMR-RIT at the minimum potency used for this study (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMR-RIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was administered 42 days after the first. The study had 10 co-primary objectives to evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti-measles and anti-rubella antibodies were measured by ELISA and anti-mumps antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT).ResultsEach formulation induced immune responses to all vaccine antigens after each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT-Med induced immune responses as measured by ELISA against the three vaccine antigens that met pre-specified non-inferiority criteria. The immune response following MMR-RIT-Med against mumps measured by PRNT failed the non-inferiority criterion for seroresponse rate: the 97.5% confidence interval lower limit (−10.94%) was beyond the pre-defined limit of −10%. Immune responses were comparable among groups post-dose 2. No safety concerns were identified, and MMR-RIT and MMR II vaccines had similar reactogenicity and safety profiles.ConclusionsOne dose of MMR-RIT formulation with lower potency (MMR-RIT-Med) induced a non-inferior immune response compared to commercial MMR II vaccine, measured by ELISA in one-year-old children. Non-inferiority was not demonstrated in terms of immune response against mumps virus measured by unenhanced PRNT, although the difference was of uncertain clinical relevance. After the second dose, immune responses were comparable among the MMR-RIT and MMR II groups.     

Inactivated infectious bronchitis virus vaccine encapsulated in chitosan nanoparticles induces mucosal immune responses and effective protection against challenge

Avian infectious bronchitis virus (IBV) is one of the most important viral diseases of poultry. The mucosa of upper respiratory tract, specially the trachea, is the primary replication site for this virus. However, conventional inactivate IBV vaccines usually elicit reduced mucosal immune responses and local protection. Thus, an inactivated IBV vaccine containing BR-I genotype strain encapsulated in chitosan nanoparticles (IBV-CS) was produced by ionic gelation method to be administered by oculo-nasal route to chickens. IBV-CS vaccine administered alone resulted in markedly mucosal immune responses, characterized by high levels of anti-IBV IgA isotype antibodies and IFNγ gene expression at 1dpi. The association of live attenuated Massachusetts IBV and IBV-CS vaccine also induced strong mucosal immune responses, though a switch from IgA isotype to IgG was observed, and IFNγ gene expression peak was late (at 5 dpi). Efficacy of IBV-CS was evaluated by tracheal ciliostasis analysis, histopathology examination, and viral load determination in the trachea and kidney. The results indicated that IBV-CS vaccine administered alone or associated with a live attenuated heterologous vaccine induced both humoral and cell-mediated immune responses at the primary site of viral replication, and provided an effective protection against IBV infection at local (trachea) and systemic (kidney) sites.     

Intradermal vaccination with un-adjuvanted sub-unit vaccines triggers skin innate immunity and confers protective respiratory immunity in domestic swine

Intradermal (ID) vaccination constitutes a promising approach to induce anti-infectious immunity. This route of immunization has mostly been studied with influenza split-virion vaccines. However, the efficacy of ID vaccination for sub-unit vaccines in relation to underlying skin innate immunity remains to be explored for wider application in humans. Relevant animal models that more closely mimic human skin immunity than the widely used mouse models are therefore necessary. Here, we show in domestic swine, which shares striking anatomic and functional properties with human skin, that a single ID delivery of pseudorabies virus (PRV) glycoproteins without added adjuvant is sufficient to trigger adaptive cellular and humoral immune responses, and to confer protection from a lethal respiratory infection with PRV. Analysis of early events at the skin injection site revealed up-regulation of pro-inflammatory cytokine and chemokine genes, recruitment of neutrophils and monocytes and accumulation of inflammatory DC. We further show that the sustained induction of pro-inflammatory cytokine genes results from the combined effects of skin puncture, liquid injection in the dermis and viral antigens. These data highlight that immune protection against respiratory infection can be induced by ID vaccination with a subunit vaccine and reveal that adjuvant requirements are circumvented by the mechanical and antigenic stress caused by ID injection, which triggers innate immunity and mobilization of inflammatory DC at the immunization site. ID vaccination with sub-unit vaccines may thus represent a safe and efficient solution for protection against respiratory infections in swine and possibly also in humans, given the similarity of skin structure and function in both species.     

Spray dried human and chimpanzee adenoviral-vectored vaccines are thermally stable and immunogenic in vivo

Cold chain-free vaccine technologies are needed to ensure effective vaccine delivery and coverage, particularly in resource-poor countries. However, the immunogenicity and thermostability of spray dried live viral vector-based vaccines such as recombinant adenoviral-vectored vaccines remain to be investigated. To address this issue, we have spray dried human adenoviral (AdHu5)- and chimpanzee adenoviral (AdCh68)-vectored tuberculosis vaccines in a mannitol and dextran matrix. Spray dried powders containing these two vaccines display the morphologic and chemical properties desired for long-term thermostability and vaccination. Upon reconstitution, they effectively transfected the cells in vitro with relatively small losses in viral infectivity related to the spray drying process. Following in vivo vaccination, AdHu5- and AdCh68-vectored vaccines were as immunogenic as the conventional fresh, cryopreserved liquid vaccine samples. Of importance, even after cold chain-free storage, at ambient temperatures and relatively low humidity for 30 and 90 days, the vaccines retained their in vivo immunogenicity, while the liquid vaccine samples stored under the same conditions lost their immune-activating capability almost entirely. Our results support further development of our spray drying technologies for generating thermally stable adenoviral-vectored and other viral-vectored vaccines.     

Recent advances in the study of live attenuated cell-cultured smallpox vaccine LC16m8

LC16m8 is a live, attenuated, cell-cultured smallpox vaccine that was developed and licensed in Japan in the 1970s, but was not used in the campaign to eradicate smallpox. In the early 2000s, the potential threat of bioterrorism led to reconsideration of the need for a smallpox vaccine. Subsequently, LC16m8 production was restarted in Japan in 2002, requiring re-evaluation of its safety and efficacy. Approximately 50,000 children in the 1970s and about 3500 healthy adults in the 2000s were vaccinated with LC16m8 in Japan, and 153 adults have been vaccinated with LC16m8 or Dryvax in phase I/II clinical trials in the USA. These studies confirmed the safety and efficacy of LC16m8, while several studies in animal models have shown that LC16m8 protects the host against viral challenge. The World Health Organization Strategic Advisory Group of Experts on Immunization recommended LC16m8, together with ACAM2000, as a stockpile vaccine in 2013. In addition, LC16m8 is expected to be a viable alternative to first-generation smallpox vaccines to prevent human monkeypox.     

Pediatric provider vaccine hesitancy: An under-recognized obstacle to immunizing children

ObjectiveTo describe vaccine attitudes among pediatric healthcare providers attending immunization conferences.Study designAttendees of 5 American Academy of Pediatrics (AAP)-sponsored vaccine conferences held between June and November 2013 anonymously completed a questionnaire assessing vaccine attitudes and practices prior to the opening of educational sessions. Pearson's chi-square tests and Fisher's exact tests were used to analyze associations between vaccine attitudes, vaccine practices and provider characteristics.Results680 providers attending AAP-sponsored vaccine conferences were included. 661/666 (99%) enrolled providers state they routinely recommend standard pediatric vaccines, yet, 30 (5%) state that they do not routinely recommend influenza and/or human papillomavirus (HPV) vaccines. These providers expressed vaccine safety (87/680 (13%)) and efficacy (21/680 (31%)) concerns and stated belief in vaccine misperceptions: vaccine causes autism (34/668, 5%), multiple vaccines at a single visit reduces vaccine efficacy (43/680, 6%) or overwhelms the immune system (63/680, 9%), and administering HPV vaccine will increase the likelihood of unprotected adolescent sexual activity (29/680, 4%). Six percent of providers who do not routinely recommend all pediatric vaccines correctly identified themselves as vaccine hesitant.ConclusionVaccine hesitancy is under-recognized among pediatric providers attending AAP-sponsored immunization conferences. Educational interventions tailored to address provider vaccine concerns are needed to improve provider vaccine confidence.     

Analysis of safety data in children after receiving two doses of ProQuad® (MMRV)

BackgroundIn randomized clinical studies, over 11,800 children, 12 months to 6 years of age, were administered ProQuad^®, a combination measles, mumps, rubella, and varicella vaccine (MMRV). This paper describes the safety following a 2-dose regimen of MMRV administered to children in the second year of life.MethodsSafety data from five clinical studies were combined for all children who were scheduled to receive two doses of MMRV ∼3–6 months apart. All vaccinated children were followed for safety following each dose of MMRV.ResultsOf 3112 children who received a first dose of MMRV, 2780 (89.3%) received a second dose of MMRV. Overall, 70.5% and 57.7% of children reported ≥1 adverse experiences following first and second doses of MMRV, respectively. Injection-site redness was statistically significantly higher postdose 2 than postdose 1, while injection-site pain/tenderness was statistically significantly higher postdose 1 compared to postdose 2. Rashes were statistically significantly lower postdose 2 compared to postdose 1. Ten febrile seizures (8 postdose 1, 2 postdose 2) were reported following MMRV vaccination. The incidence of febrile seizures postdose 1 of MMRV was 0.26% (8/3019) compared to 0.07% (2/2695) postdose 2 of MMRV.ConclusionsAdministration of two doses of MMRV has an acceptable safety profile in children 12 to 23 months of age. There is a small increase in the risk of febrile seizures following the first dose of MMRV as compared to the component vaccines, but the risk for any individual child is relatively low.     

Supplemental measles vaccine antibody response among HIV-infected and -uninfected children in Malawi after 1- and 2-dose primary measles vaccination schedules

BackgroundThe long-term antibody response to measles vaccine (MV) administered at age 6 months with or without subsequent doses is not well documented.MethodsMeasles serum antibody responses were evaluated after a supplemental dose of measles vaccine (sMV) administered at a median age of 20 months among Malawian children who had previously received 2 doses of measles vaccine (MV) at ages 6 and 9 months (HIV-infected and random sample of HIV-uninfected) or 1 dose at age 9 months (random sample of HIV-uninfected). We compared measles antibody seropositivity between groups by enzyme linked immunoassay and seroprotection by plaque reduction neutralization geometric mean concentrations.ResultsOf 1756 children enrolled, 887 (50.5%) received a sMV dose following MV at 9 months of age and had specimens available after sMV receipt, including 401 HIV-uninfected children who received one MV dose at 9 months, 464 HIV-uninfected and 22 HIV-infected children who received two doses of MV at ages 6 and 9 months. Among HIV-uninfected children, protective levels of antibody were found post sMV in 90–99% through ages 24–36 months and were not affected by MV schedule. Geometric mean concentration levels of measles antibody were significantly increased post-sMV among those HIV-uninfected children previously non-responsive to vaccination. Among HIV-infected children, the proportion seroprotected increased initially but by 9 months post-sMV was no higher than pre-sMV.ConclusionsOur findings support early 2-dose MV to provide measles immunity for young infants without risk of interference with antibody responses to subsequent MV doses administered as part of SIAs.     

Successive introduction of four new vaccines in Rwanda: High coverage and rapid scale up of Rwanda's expanded immunization program from 2009 to 2013

As the pace of vaccine uptake accelerates globally, there is a need to document low-income country experiences with vaccine introductions. Over the course of five years, the government of Rwanda rolled out vaccines against pneumococcus, human papillomavirus, rotavirus, and measles & rubella, achieving over 90% coverage for each. To carry out these rollouts, Rwanda's Ministry of Health engaged in careful review of disease burden information and extensive, cross-sectoral planning at least one year before introducing each vaccine. Rwanda's local leaders, development partners, civil society organizations and widespread community health worker network were mobilized to support communication efforts. Community health workers were also used to confirm target population size. Support from Gavi, UNICEF and WHO was used in combination with government funds to promote country ownership and collaboration. Vaccination was also combined with additional community-based health interventions. Other countries considering rapid consecutive or simultaneous rollouts of new vaccines may consider lessons from Rwanda's experience while tailoring the strategies used to local context.     

Induction of CD8+ T cell responses and protective efficacy following microneedle-mediated delivery of a live adenovirus-vectored malaria vaccine

There is an urgent need for improvements in vaccine delivery technologies. This is particularly pertinent for vaccination programmes within regions of limited resources, such as those required for adequate provision for disposal of used needles. Microneedles are micron-sized structures that penetrate the stratum corneum of the skin, creating temporary conduits for the needle-free delivery of drugs or vaccines. Here, we aimed to investigate immunity induced by the recombinant simian adenovirus-vectored vaccine ChAd63.ME-TRAP; currently undergoing clinical assessment as a candidate malaria vaccine, when delivered percutaneously by silicon microneedle arrays. In mice, we demonstrate that microneedle-mediated delivery of ChAd63.ME-TRAP induced similar numbers of transgene-specific CD8⁺ T cells compared to intradermal (ID) administration with needle-and-syringe, following a single immunisation and after a ChAd63/MVA heterologous prime-boost schedule. When mice immunised with ChAd63/MVA were challenged with live Plasmodium berghei sporozoites, microneedle-mediated ChAd63.ME-TRAP priming demonstrated equivalent protective efficacy as did ID immunisation. Furthermore, responses following ChAd63/MVA immunisation correlated with a specific design parameter of the array used (‘total array volume’). The level of transgene expression at the immunisation site and skin-draining lymph node (dLN) was also linked to total array volume. These findings have implications for defining silicon microneedle array design for use with live, vectored vaccines.     

A recombinant varicella vaccine harboring a respiratory syncytial virus gene induces humoral immunity

The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is highly efficient and causes few adverse events; therefore, it is used worldwide. We previously constructed recombinant vOka (rvOka) harboring the mumps virus gene. Immunizing guinea pigs with rvOka induced the production of neutralizing antibodies against the mumps virus and VZV.Here, we constructed recombinant vOka viruses containing either the respiratory syncytial virus (RSV) subgroup A fusion glycoprotein (RSV A–F) gene or RSV subgroup B fusion glycoprotein (RSV B–F) gene (rvOka-RSV A–F or rvOka-RSV B–F). Indirect immunofluorescence and Western blot analyses confirmed the expression of each recombinant RSV protein in virus-infected cells. Immunizing guinea pigs with rvOka-RSV A–F or rvOka-RSV B–F led to the induction of antibodies against RSV proteins. These results suggest that the current varicella vaccine genome can be used to generate custom-made vaccine vectors to develop the next generation of live vaccines.     

Combined semi-empirical screening and design of experiments (DOE) approach to identify candidate formulations of a lyophilized live attenuated tetravalent viral vaccine candidate

A combination experimental approach, utilizing semi-empirical excipient screening followed by statistical modeling using design of experiments (DOE), was undertaken to identify stabilizing candidate formulations for a lyophilized live attenuated Flavivirus vaccine candidate. Various potential pharmaceutical compounds used in either marketed or investigative live attenuated viral vaccine formulations were first identified. The ability of additives from different categories of excipients, either alone or in combination, were then evaluated for their ability to stabilize virus against freeze-thaw, freeze-drying, and accelerated storage (25 °C) stresses by measuring infectious virus titer. An exploratory data analysis and predictive DOE modeling approach was subsequently undertaken to gain a better understanding of the interplay between the key excipients and stability of virus as well as to determine which combinations were interacting to improve virus stability. The lead excipient combinations were identified and tested for stabilizing effects using a tetravalent mixture of viruses in accelerated and real time (2–8 °C) stability studies. This work demonstrates the utility of combining semi-empirical excipient screening and DOE experimental design strategies in the formulation development of lyophilized live attenuated viral vaccine candidates.     

A West Nile virus NS4B-P38G mutant strain induces cell intrinsic innate cytokine responses in human monocytic and macrophage cells

Previous studies have shown that an attenuated West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant induces stronger innate and adaptive immune responses than wild-type WNV in mice, which has important applications to vaccine development. To investigate the mechanism of immunogenicity, we characterized WNV NS4B-P38G mutant infection in two human cell lines—THP-1 cells and THP-1 macrophages. Although the NS4B-P38G mutant produced more viral RNA than the parental WNV NY99 in both cell types, there was no detectable infectious virus in the supernatant of either cell type. Nonetheless, the attenuated mutant boosted higher innate cytokine responses than virulent parental WNV NY99 in these cells. The NS4B-P38G mutant infection of THP-1 cells led to more diverse and robust innate cytokine responses than that seen in THP-1 macrophages, which were mediated by toll-like receptor (TLR)7 and retinoic acid-inducible gene 1(RIG-I) signaling pathways. Overall, these results suggest that a defective viral life cycle during NS4B-P38G mutant infection in human monocytic and macrophage cells leads to more potent cell intrinsic innate cytokine responses.     

Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation

Sublethal γ irradiation eliminates CD8+ T cell mediated memory responses. In this work, we explored how these memory responses could be rescued in the aftermath of such exposure. We utilized two models of CD8+ T cell mediated immunity: a mouse model of Listeria monocytogenes (LM) infection in which CD8+ T cells specific for LM expressed antigens (Listeriolysin O, LLO) can be tracked, and a murine skin graft model in which CD8+ T cells mediate rejection across a MHC class I (D^d) disparity. In the LM immunized mice, LL0 specific CD8+ T memory cells were lost on irradiation, preserved with rapid revaccination with an attenuated strain 1–3 days post-irradiation (PI), and these mice survived a subsequent wild type LM challenge. A genetic “signature of rescue” identified a group of immune-associated mRNA maintained or upregulated following irradiation and rescue. A number of these factors, including IL-36γ, dectin-2 (Clec4n), and mir101c are upregulated rapidly after exposure of mice to sublethal γ radiation alone and are sustained by early, but not later rescue. Such factors will be evaluated as potential therapeutics to replace individual vaccines for global rescue of CD8+ T memory cell responses following sublethal γ irradiation. The skin allograft model mirrored that of the LM model in that the accelerated D^d skin allograft rejection response was lost in mice exposed to sublethal γ radiation, but infusion of allogeneic D^d expressing bone marrow cells 1–4 days PI preserved the CD8+ T memory mediated accelerated rejection response, further suggesting that innate immune responses may not always be essential to rescue of CD8+ memory T cells following γ irradiation.     

Neutralising antibody response in domestic cats immunised with a commercial feline immunodeficiency virus (FIV) vaccine

Across human and veterinary medicine, vaccines against only two retroviral infections have been brought to market successfully, the vaccines against feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV). FeLV vaccines have been a global success story, reducing virus prevalence in countries where uptake is high. In contrast, the more recent FIV vaccine was introduced in 2002 and the degree of protection afforded in the field remains to be established. However, given the similarities between FIV and HIV, field studies of FIV vaccine efficacy are likely to advise and inform the development of future approaches to HIV vaccination.Here we assessed the neutralising antibody response induced by FIV vaccination against a panel of FIV isolates, by testing blood samples collected from client-owned vaccinated Australian cats. We examined the molecular and phenotypic properties of 24 envs isolated from one vaccinated cat that we speculated might have become infected following natural exposure to FIV. Cats vaccinated against FIV did not display broadly neutralising antibodies, suggesting that protection may not extend to some virulent recombinant strains of FIV circulating in Australia.     

On birth single dose live attenuated OPV and BCG vaccination induces gut cathelicidin LL37 responses at 6 week of age: A natural experiment

In a cross sectional study, we show that infants who received single dose of live attenuated OPV and BCG vaccines within 48 h of birth, have higher excretion of human cathelicidin LL37 (p < 0.05) in stool at 6 wk of age. This response remained unchanged in multivariate analysis after adjusting for sex, mode of delivery, infant age, mother age birth weight and breast milk feeding pattern. This analysis also reveals that irrespective of vaccination, girl infants have higher human-beta-defencin2 (HBD2) and exclusively breastfed infants have higher total and anti-polio specific IgA to all three subtypes in stool (p < 0.05). However, vaccination induces anti-polio IgA responses only to infants who are exclusively breastfed. Thus on-birth live attenuated vaccination may provide non-specific beneficial effect against infections while exclusive breastfeeding enhance protection by boosting vaccine induced IgA. The result also suggests that in polio endemic area, exclusive breastfeeding may be sufficient for mucosal anti-polio responses during early infancy.     

Completion and compliance of childhood vaccinations in the United States

BackgroundThe Advisory Committee on Immunization Practices recommends routine childhood vaccination by age 2 years, yet evidence suggests that only 2% to 26% of children receive vaccine doses at age-appropriate times (compliance). The objective of this study was to estimate vaccine completion and compliance rates between birth and age 2 years using recent, nationally representative data.MethodsUsing a sample of children aged 24 to 35 months from the 2012 National Immunization Survey (NIS), the present study examined completion and compliance of recommended childhood vaccines. A state-specific examination of vaccine completion and compliance was also conducted.ResultsAn unweighted sample of 11,710 children (weighted to 4.1 million) was selected. Approximately 70% of children completed all doses of six recommended vaccines by 24 months of age. Completion rates varied by antigen, ranging from 68% completing two or three doses of rotavirus vaccine to 92% completing three doses of inactivated poliovirus vaccine. Vaccine completion rates also varied at different measurement periods, with the lowest rates observed at 18 months. Approximately 26% of children received all doses of six recommended vaccines on time. Among the 74% of children who received at least one late dose, 39% had >7 months of undervaccination. Patterns of completion and compliance also varied by geographic region.ConclusionsCompletion of individual antigens approached Healthy People 2020 targets. However, overall completion of the recommended vaccine series and compliance with the recommended vaccination dosing schedule were low, indicating few children received vaccines at age-appropriate times. Additional clinical, policy, and educational interventions are needed to increase receipt of vaccines at optimal ages.