Development of competitive inhibition ELISA as an effective potency test to analyze human rabies vaccines and assessment of the antigenic epitope of rabies glycoprotein.

The potency of all modern tissue culture human rabies vaccines is measured based on the National Institute of Health (NIH) potency test that is laborious, time-consuming, involves large test variations and requires sacrifice of large number of animals. To circumvent these limitations, several researchers and WHO expert working groups have discussed development of alternative in vitro methods to replace the NIH potency test. Although several immunochemical methods have been proposed to quantify rabies glycoprotein (G-protein) using multiple murine monoclonal antibodies, we report an In vitro competitive inhibition ELISA (CIA) method based on the use of a neutralizing rabies glycoprotein site III directed novel therapeutic human rabies monoclonal antibody (RAB1) that shows equivalence to the mice NIH potency test in recognition of neutralization site of the glycoprotein. In vitro potency testing of WHO 7th International Standard for rabies vaccine (IS) by CIA using RAB1 and In-house reference standard (IHRS) as a standard to assess its suitability for the assessment of validation parameters showed accurate and precise values with <15% coefficient variance. The method was validated using 5PL standard curve with linearity r2 > 0.98 and LLOQ of 0.125 IU/mL indicating sensitivity of the method. The method was found to be precise, robust and accurate to quantitate intact rabies glycoprotein in final vaccine and showed a strong correlation (Pearson's r = 0.81) with the NIH potency values of licensed Vero cell rabies vaccine. The CIA test using RAB1 was able to accurately quantitate degradation of rabies vaccine and assess loss in antigenicity of lyophilized and reconstituted liquid rabies vaccine under thermal stress conditions. The method was able to differentiate between potent and reduced potency vaccine samples. The new in vitro competitive inhibition ELISA method using RAB1 thus can be a valid alternative to the NIH test.

Long-term efficacy of BCG vaccination in goat herds with a high prevalence of tuberculosis.

Vaccination of goats against tuberculosis (TB) has been promoted as an ancillary tool for controlling the disease in infected livestock herds. A three-year trial to assess the efficacy of BCG vaccine was carried out in five goat herds. At the beginning of the trial (month 0), all animals were tested for TB using thee different diagnostic tests. Animals negative to all tests were vaccinated with BCG and all replacement goat kids were also systematically vaccinated throughout the trial. All animals were tested by Interferon-gamma release assay (IGRA) using vaccine compatible reagents at months 6, 12, 24, and 36. The risk factors for TB infection were also evaluated. At the end of the study, four out of five farms showed variable reductions of the initial prevalence (93.5%, 28.5%, 23.2%, and 14.3% respectively), and an overall incidence reduction of 50% was observed in BCG vaccinated goats, although adult vaccinated goats showed higher incidences than vaccinated goat kids. The unvaccinated positive animals remaining in herds and adult BCG vaccinated goats significantly enhanced the risk of infection in vaccinated animals. A systematic vaccination of goats with BCG, together with the removal of positive unvaccinated animals, may contribute to reducing the TB prevalence in goat herds.

Replacing the in vivo toxin challenge test with an in vitro assay for assessment of potency for diphtheria toxoid containing vaccines.

Replacement of the potency tests for diphtheria vaccines is a high priority for the international initiative to reduce, refine, and replace animal use in vaccine testing. Diphtheria toxoid containing vaccine products marketed in the US currently require potency testing by the United States Public Health Service (USPHS) test, which includes an in vivo passive protection test with a diphtheria toxin challenge. Here we describe an in vitro Diphtheria Vero Cell (DVC) assay which combines the immunization approach from the USPHS test and the use of a cell based neutralization assay for serological testing of vaccine potency. The DVC assay reduces the overall number of animals used compared to other serological potency tests and eliminates the in vivo toxin challenge used in the US test. The DVC assay can be used to test vaccine products with a low or high diphtheria toxoid dose. It has been optimized and validated for use in a quality control testing environment. Results demonstrate similar sera antibody unitage as well as agreement between the serum neutralization values determined using the USPHS test and the DVC assay and thus support the use of the DVC assay for routine and stability testing for diphtheria toxoid containing vaccine products.

Rotavirus Vaccine Effectiveness against the Risk of Hospitalization and the Impact of Using Public Funds for the Vaccine on a Regional Rotavirus Gastroenteritis Epidemic in Japan.

An epidemic of rotavirus (RV) gastroenteritis occurred from April to July 2015 across a wide area of Hokkaido, surrounding the Abashiri-Kosei General Hospital. The RV vaccine for children in Shari and Koshimizu was provided at public funds by their local governments, while children in Abashiri were charged for the vaccine. This study examined the effectiveness of the RV vaccine against the risk of hospitalization based on a retrospective cohort study and the impact of using public funds for RV vaccination on a regional RV gastroenteritis epidemic. The vaccination coverage was significantly higher in children in Shari and Koshimizu than in Abashiri (87.8% vs. 42.7%, respectively, p < 0.001). The RV gastroenteritis-related risk of hospitalization was slightly lower in children from Shari and Koshimizu than in those from Abashiri (1.6% vs. 3.2%, respectively, p = 0.07). In addition, the risk of hospitalization in the vaccinated children was significantly lower than that in the unvaccinated children (0.7% vs. 4.8%, respectively, p < 0.001); indicating that the RV vaccine effectiveness against the risk of hospitalization was 96.5% (95% confidence interval 45.7%-99.8%). In conclusion, the use of public funds for the provision of RV vaccine increased the vaccination coverage, which, in combination with high vaccine effectiveness, led to a decrease in the number of hospitalizations in children during a regional RV gastroenteritis epidemic.

[Genetic characterization of influenza A virus and assessment of vaccine efficacy in Yantai from 2014 to 2017].

In this study, the swabs were collected among patients with an influenza-like illness (ILI) admitted to 2 sentinel surveillance hospitals of Yantai from April 2014 to August 2017. All specimen were cultured and identified by hemagglutination inhibition assay. Complete sequences of Hemagglutinin (HA) of influenza A were amplified, sequenced and analyzed using molecular and phylogenetic methods. The potential vaccine efficacy were calculated using Pepitope model. The results showed that the antigenicity of A (H3N2) had changed greatly. 8 strains of influenza A (H1N1) pdm09 belonged to subclade 6B.1 and 14 strains clustered in 6B.2. 12 strains of influenza A (H3N2) fell into subgroup 3C.3a and 33 strains clustered in 3C.2a. Several residues at antigen sites and potential glycosylation sites had changed in influenza A strains. Vaccine efficacy of influenza A (H1N1) pdm09 in 2015/2016 and 2016/2017 seasons were 77.29% and 79.11% of that of a perfect match with vaccine strain, meanwhile vaccine efficacy of influenza A (H3N2) in 2014/2015, 2015/2016 and 2016/2017 were-5.18%, 16.97% and 42.05% separately. In conclusion, the influenza A virus circulated in Yantai from 2014 to 2017 presented continual genetic variation. The recommended vaccine strains still afforded protection against influenza A (H1N1) pdm09 strains and provided suboptimal protection against influenza A (H3N2) strains.

A systematic literature review and network meta-analysis feasibility study to assess the comparative efficacy and comparative effectiveness of pneumococcal conjugate vaccines.

Background: No head-to-head studies are currently available comparing pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with 13-valent pneumococcal conjugate vaccine (PCV-13). This study explored the feasibility of using network meta-analysis (NMA) to conduct an indirect comparison of the relative efficacy or effectiveness of the two vaccines.Methods: A systematic literature search was conducted for published randomized controlled trials (RCTs) and non-RCT studies reporting data on vaccine efficacy or effectiveness against invasive pneumococcal disease in children aged <5 years receiving 7-valent pneumococcal conjugate vaccine (PCV-7), PHiD-CV or PCV-13. Study quality was evaluated using published scales. NMA feasibility was assessed by considering whether a connected network could be constructed by examining published studies for differences in study or patient characteristics that could act as potential treatment effect modifiers or confounding variables.Results: A total of 26 publications were included; 2 RCTs (4 publications), 7 indirect cohort studies, and 14 case-control studies (15 publications). Study quality was generally good. The RCTs could not be connected in a network as there was no common comparator. The studies differed considerably in design, dose number, administration schedules, and subgroups analyzed. Reporting of exposure status and subject characteristics was inconsistent.Conclusion: NMA to compare the relative efficacy or effectiveness of PHiD-CV and PCV-13 is not feasible on the current evidence base, due to the absence of a connected network across the two RCTs and major heterogeneity between studies. NMA may be possible in future if sufficient RCTs become available to construct a connected network.

Comparative Assessment of the Whole-cell Pertussis Vaccine Potency Using Serological and Intracerebral Mouse Protection Methods.

One of the most important QC tests of whole-cell pertussis vaccine (WCPV) is potency test. In this regard, mouse protection test (MPT) is the current potency method, which is associated with severe animal distress and large variability in results. The purpose of this study was to assess Pertussis Serological Potency Test (PSPT) as a serological alternative method to intracerebral challenge in MPT assay. In the current study, the potency of three experimental batches of WCPV (1, 2, and 3) and standard vaccine were compared using MPT and PSPT methods. In the MPT method, mice were immunized with tests and standard vaccines. After 2 weeks, they were intracerebrally challenged with Bordetella pertussis strain (18323). The potency was calculated via parallel line analysis based on the numbers of survivors 2 weeks after the challenge. Similar to MPT method, mice were immunized in the PSPT method and bled after 4 weeks. In the next step, sera were titrated by 18323-WCP-ELISA assay and potency values were estimated via parallel line analysis. Pearson correlation test was used to measure the strength of association between MPT and PSPT assay results. The potency values of the experimental laboratory batches 1, 2, and 3 in MPT assays were 11.14, 5.02, and 4.24 Iu/ml, whereas the obtained results of PSPT assays were 10.32, 4.11, and 3.06 Iu/ml, respectively. The correlation of MPT and PSPT results was 0.807. The findings of the present study demonstrated a significant correlation between MPT and PSPT results. The implementation of PSPT was more advantageous, compared to MPT due to its ethical approaches and less variability in results. The PSPT is a promising alternative method for intracerebral challenge. However, additional validation is needed to support the establishment of this method.

Effect of propensity of seeking medical care on the bias of the estimated effectiveness of rotavirus vaccines from studies using a test-negative case-control design.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea among children worldwide, and vaccines can reduce morbidity and mortality by 50-98%. The test-negative control (TNC) study design is increasingly used for evaluating the effectiveness of vaccines against rotavirus and other vaccine-preventable diseases. In this study design, symptomatic patients who seek medical care are tested for the pathogen of interest. Those who test positive (negative) are classified as cases (controls). METHODS: We use a probability model to evaluate the bias of estimates of rotavirus vaccine effectiveness (VE) against rotavirus diarrhea resulting in hospitalization in the presence of possible confounding and selection biases due to differences in the propensity of seeking medical care (PSMC) between vaccinated and unvaccinated children. RESULTS: The TNC-based VE estimate corrects for confounding bias when the confounder's effects on the probabilities of rotavirus and non-rotavirus related hospitalizations are equal. If this condition is not met, then the estimated VE may be substantially biased. The bias is more severe in low-income countries, where VE is known to be lower. Under our model, differences in PSMC between vaccinated and unvaccinated children do not result in selection bias when the TNC study design is used. CONCLUSIONS: In practice, one can expect the association of PSMC (or other potential confounders) with the probabilities of rotavirus and non-rotavirus related hospitalization to be similar, in which case the confounding effects will only result in small bias in the VE estimate from TNC studies. The results of this work, along with those of our previous paper, confirm the TNC design can be expected to provide reliable estimates of rotavirus VE in both high- and low-income countries.

Thermal Stabilization of Viral Vaccines in Low-Cost Sugar Films.

Most currently available vaccines, particularly live vaccines, require the cold chain, as vaccine efficacy can be significantly hampered if they are not stored in a temperature range of 2-8 °C at all times. This necessity places a tremendous financial and logistical burden on vaccination programs, particularly in the developing world. The development of thermally stable vaccines can greatly alleviate this problem and, in turn, increase vaccine accessibility worldwide. In this paper, we detail a simple and cost-effective method for stabilizing live vaccines that uses FDA-approved materials. To this end, we dried enveloped DNA (Herpes Simplex Virus type 2) and RNA (Influenza A virus) viral vaccines in a pullulan and trehalose mixture. The results of these studies showed that the live-attenuated HSV-2 vaccine retained its efficacy for at least 2 months of storage at 40 °C, while the inactivated influenza vaccine was able to retain its immunogenicity for at least 3 months of storage at 40 °C. This work presents a simple approach that allows thermo-sensitive vaccines to be converted into thermo-stable vaccines that do not require refrigeration, thus contributing to the improvement of vaccine deployment throughout the world.

Modeling indicates efficient vaccine-based interventions for the elimination of hepatitis C virus among persons who inject drugs in metropolitan Chicago.

BACKGROUND AND AIMS: Persons who inject drugs (PWID) are at highest risk for acquiring and transmitting hepatitis C (HCV) infection. The recent availability of oral direct-acting antiviral (DAA) therapy with reported cure rates >90% can prevent HCV transmission, making HCV elimination an attainable goal among PWID. The World Health Organization (WHO) recently proposed a 90% reduction in HCV incidence as a key objective. However, given barriers to the use of DAAs in PWID, including cost, restricted access to DAAs, and risk of reinfection, combination strategies including the availability of effective vaccines are needed to eradicate HCV as a public health threat. This study aims to model the cost and efficacy of a dual modality approach using HCV vaccines combined with DAAs to reduce HCV incidence by 90% and prevalence by 50% in PWID populations. METHODS: We developed a mathematical model that represents the HCV epidemic among PWID and calibrated it to empirical data from metropolitan Chicago, Illinois. Four medical interventions were considered: vaccination of HCV naive PWID, DAA treatment, DAA treatment followed by vaccination, and, a combination of vaccination and DAA treatment. RESULTS: The combination of vaccination and DAAs is the lowest cost-expensive intervention for achieving the WHO target of 90% incidence reduction. The use of DAAs without a vaccine is much less cost-effective with the additional risk of reinfection after treatment. Vaccination of naïve PWID alone, even when scaled-up to all reachable PWID, cannot achieve 90% reduction of incidence in high-prevalence populations due to infections occurring before vaccination. Similarly, the lowest cost-expensive way to halve prevalence in 15 years is through the combination of vaccination and DAAs. CONCLUSIONS: The modeling results underscore the importance of developing an effective HCV vaccine and augmenting DAAs with vaccines in HCV intervention strategies in order to achieve efficient reductions in incidence and prevalence.

Assessment of the safety and efficacy of an attenuated live vaccine based on highly virulent genotype 2b porcine epidemic diarrhea virus in nursing piglets.

We have previously reported the generation of the attenuated KNU-141112-S DEL5/ORF3 virus by continuous propagation of highly virulent G2b porcine epidemic diarrhea virus (PEDV) in Vero cells. The present study aimed to assess the safety of S DEL5/ORF3 and to evaluate its effectiveness as a live vaccine for prime-booster vaccinations. Reversion to virulence experiments revealed that the S DEL5/ORF3 strain retains its attenuated phenotype and genetic stability after five successive passages in susceptible piglets. Pregnant sows were primed orally with an S DEL5/ORF3 live vaccine and boosted intramuscularly twice with a commercial killed vaccine at 2-week intervals prior to parturition. This sow vaccination regimen completely protected nursing piglets against virulent G2b challenge, as evidenced by the increase in survival rate from 0% to 100% and the significant reduction in diarrhea intensity, including the amount and duration of PEDV fecal shedding. In addition, despite a 2-3 day period of weight loss in piglets from vaccinated sows after challenge, their daily weight gain was recovered at 7 days post-challenge and became similar to that of unchallenged pigs from unvaccinated sows over the course of the experiment. Furthermore, strong antibody responses to PEDV were verified in the sera and colostrum of immunized sows with the prime-boost treatment and their offspring. Altogether, our data demonstrated that the attenuated S DEL5/ORF3 strain guarantees the safety to host animals with no reversion to virulence and is suitable as an effective primary live vaccine providing durable maternal lactogenic immunity for passive piglet protection.

Epidemiologic challenges in norovirus vaccine development.

Norovirus is the leading cause of acute gastroenteritis (AGE) worldwide. In the United States norovirus is estimated to cause 19-21 million illnesses, 1.7-1.9 million outpatient visits, 56,000-71,000 hospitalizations, and 570-800 deaths annually. Through direct costs and loss of productivity, norovirus disease cost the US economy more than $5.5 billion annually. Due to the lack of available therapies to treat norovirus infections and their highly infectious nature, preventing norovirus illness through vaccination is an appealing strategy. Currently, several norovirus vaccines are in development, including five vaccines in preclinical trials, an oral monovalent vaccine (Vaxart, Inc.) that recently completed a phase IB clinical trial, and a bivalent intramuscular vaccine (Takeda Pharmaceutical Company Limited) in a phase IIB clinical trial. However, no norovirus vaccines are currently available on the market. In this commentary we aim to describe some of the barriers faced in norovirus vaccine development, particularly focusing on vaccine effectiveness and defining the target population.

Oral cholera vaccines and their impact on the global burden of disease.

With one-third of nations at risk of cholera, we can expect to experience massive, rapidly disseminated, and prolonged cholera outbreaks such as those recently experienced in Yemen and Haiti. The prevention of cholera outbreaks like these includes the provision of potable water, sanitation, and hygiene (WASH). This approach has been known for generations. However, it will be many years before universal global access to WASH is achieved. While working toward universal WASH, study data has shown that licensed and WHO prequalified cholera vaccines are important tools for cholera prevention. Oral inactivated whole-cell vaccines such as Shanchol and Euvichol-plus provide well-documented direct benefits to vaccine recipients and to the unimmunized through herd protection. Manufacturers have now increased the cholera vaccine supply, and since 2013 vaccine doses have been available for emergency and endemic control through a global stockpile. Advances in packaging and vaccine temperature control, reduced vaccine costs, the inclusion of pregnant women in vaccine campaigns, and a targeted approach to high incidence endemic areas are further increasing the usefulness of these vaccines for reducing the global cholera burden.

Overview of antibody-mediated immunity to S. pneumoniae: pneumococcal infections, pneumococcal immunity assessment, and recommendations for IG product evaluation.

Streptococcus pneumoniae (S. pneumoniae) strains colonize the nasopharynx and can cause mucosal infections in the upper airway and middle ear, pneumonias, and invasive infections like bacteremia, sepsis, and meningitis. Over 90 serotypes, defined by the structure of their capsular polysaccharides, are known. Twenty-three of these serotypes cause most infections and several of these serotypes can develop antibiotic resistance. Susceptibility factors that increase the susceptibility to S. pneumoniae mucosal and invasive infections include all forms of primary and secondary antibody deficiencies. Many patients affected by one of these deficiencies benefit from the regular administration of human gamma globulin (IgG) preparations. Donors of plasma units used to prepare human IgG have varying concentrations of IgG antibodies against relevant S. pneumoniae serotypes. These antibodies are developed in response to colonization and common subclinical infections and by routine vaccination with S. pneumoniae polysaccharide vaccines. The presence of an adequate concentration of these protective antibodies against all prevalent serotypes needs to be determined to assure the effectiveness of human IgG. All presently available methods to assess IgG antibodies against S. pneumoniae capsular polysaccharides have advantages and pitfalls that are analyzed in this review. In vitro testing does not provide a complete or necessarily accurate measurement of the effectiveness of antibodies in vivo. For regulatory purposes, caution needs to be used in the interpretation of currently available assays that measure pneumococcal antibody levels. Monitoring S. pneumoniae infections in patients treated with IgG and tracing information about IgG lots used to treat these patients should be encouraged.

Preferences for vaccines against children's diarrheal illness among mothers in Poland and Hungary.

PURPOSE: Although the World Health Organization recommends universal rotavirus immunization, uptake of the vaccine is low in Poland and Hungary, where it is not covered by the National Immunization Program. This study aimed to quantify mothers' preferences for vaccines preventing children's diarrheal illness and to examine whether willingness to vaccinate varies with working status. METHODS: Mothers of children aged <3 years living in Poland and Hungary completed an online discrete-choice experiment survey. In each of 9 choice questions, respondents indicated whether they preferred no vaccination or one of two hypothetical vaccine profiles described in terms of 6 features. Vaccine preference parameters were estimated for working and non-working mothers using a random-parameter logit model and were used to calculate the relative importance of changes in vaccine features. RESULTS: 350 mothers in Poland and 350 mothers in Hungary were surveyed. Of the attributes evaluated, changes in vaccine cost were most important in both countries, followed by changes in severity of illness prevented, vaccine effectiveness, mode of administration, duration of illness prevented, and number of doses. Mothers in both countries had a strong preference for vaccination versus no vaccination, which was more pronounced among working mothers. In Poland, working mothers placed less weight on effectiveness, illness severity, and cost than non-working mothers and were more likely to rate disruptions in work, child care, and routines as important reasons to vaccinate. In Hungary, working mothers were statistically significantly less likely to opt out of vaccination than non-working mothers. Preference for vaccination itself, relative to improving vaccine effectiveness (from 50% to 90% effective), was 7 times greater among working than among non-working mothers in Poland but was not considerably different between working and non-working mothers in Hungary. CONCLUSIONS: Polish and Hungarian working mothers are more likely to vaccinate children against diarrheal illness than non-working mothers.

Introduction to the SAVE study (2011-15): Streptococcus pneumoniae serotyping and antimicrobial susceptibility: Assessment for Vaccine Efficacy in Canada after the introduction of PCV-13.

Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally can assist in determining trends across geographical areas and allow comparisons between countries. SAVE is an ongoing, annual, national study focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. This Supplement documents the initial 5 years of the SAVE study (2011-15) during which 6207 invasive isolates of S. pneumoniae were evaluated. The three manuscripts in this Supplement provide a comprehensive examination of the changing patterns of invasive S. pneumoniae obtained across Canada over a 5 year period. The data highlight the evolution of S. pneumoniae antimicrobial resistance and multidrug resistance, serotype distribution, genotypic relatedness and virulence under pressure by vaccination and antimicrobial usage. This allows both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada.

Updates on Influenza Vaccination in Children.

Influenza vaccination is recommended for all children 6 months of age and older who do not have contraindications. This article provides an overview of information concerning burden of influenza among children in the United States; US-licensed influenza vaccines; vaccine immunogenicity, effectiveness, and safety; and recent updates relevant to use of these vaccines in pediatric populations. Influenza antiviral medications are discussed. Details concerning vaccine-related topics may be found in the current US Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices recommendations for use of influenza vaccines (https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html). Additional information on influenza antivirals is located at https://www.cdc.gov/flu/professionals/antivirals/index.htm.

The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical Trials Registration: NCT01517191.

Overall effectiveness of pneumococcal conjugate vaccines: An economic analysis of PHiD-CV and PCV-13 in the immunization of infants in Italy.

Pneumococcal diseases are associated with a significant clinical and economic burden. The 7-valent pneumococcal conjugate vaccine (PCV-7) has been used for the immunization of newborns against invasive pneumococcal diseases (IPD) in Italy while now, the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are available. The aim of this analysis was to compare the estimated health benefits, cost and cost-effectiveness of immunization strategies vs. non-vaccination in Italy using the concept of overall vaccine effectiveness. A published Markov model was adapted using local data wherever available to compare the impact of neonatal pneumococcal vaccination on epidemiological and economic burden of invasive and non-invasive pneumococcal diseases, within a cohort of newborns from the Italian National Health Service (NHS) perspective. A 18-year and a 5-year time horizon were considered for the base-case and scenario analysis, respectively. PHiD-CV and PCV-13 are associated with the most important reduction of the clinical burden, with a potential marginal advantage of PHiD-CV over PCV-13. Compared with no vaccination, PHiD-CV is found on the higher limit of the usually indicated willingness to pay range (30,000 - 50,000€/quality-adjusted life year [QALY] gained), while the incremental cost-effectiveness ratio (ICER) for PCV-13 is slightly above. Compared with PCV-13, PHiD-CV would provide better health outcomes and reduce costs even at parity price, solely due to its differential effect on the incidence of NTHi acute otitis media (AOM). The analysis on a shorter time horizon confirms the direction of the base-case.