Inactivated Polio Vaccine Research Articles

Immunogenicity of sequential poliovirus vaccination schedules with different strains of poliomyelitis vaccines in Chongqing, China: a cross-sectional survey

ABSTRACT A new vaccination schedule with one dose of inactivated polio vaccine (IPV) followed by three doses of bivalent oral attenuated live polio vaccine (bOPV) was introduced in China in 2016. Both Sabin IPV (sIPV) and Salk IPV (wIPV) sequentially with bOPV were accepted in the Chinese routine vaccination schedule. We intended to assess the immunogenicity of the current primary schedule (s/wIPV-bOPV-bOPV) and the schedule in the early stage of the switch (tOPV-bOPV-bOPV), and compare immunogenicity between the groups with different polio virus strains. Healthy infants aged 60–89 days were recruited in hospitals in Chongqing. Infants were assigned to one of three treatments (tOPV-bOPV-bOPV, sIPV-bOPV-bOPV or wIPV-bOPV-bOPV) by enrollment time. Polio neutralizing antibody (NA) assays were conducted to assess immunity. 1027 eligible infants were enrolled. Over 95% seroprotection rates against type I poliovirus (PV1) and type III poliovirus (PV3) were observed in all groups. Infants who received tOPV-bOPV-bOPV had higher antibody titers against type II poliovirus (PV2) than did the IPV-bOPV-bOPV. The geometric mean titers (GMTs) of PV2 were only ~20 in the IPV-bOPV-bOPV. GMTs of PV1 were higher than PV3 in s/wIPV-bOPV-bOPV. The primary schedule of s/wIPV-bOPV-bOPV is insufficient to protect children against PV2, and the NA titer to PV3 is lower. Higher antibody responses were induced in sIPV-bOPV-bOPV than that in wIPV-bOPV-bOPV. Supplementary vaccination with one dose of IPV is necessary for children who had no tOPV immune history or had only one IPV to induce higher levels of immunity against PV2 and PV3.

Stopping Oral Polio Vaccine (OPV) after Defeating Poliomyelitis: A Pyrrhic Victory? Systematic Review of the Non-Specific Effects of OPV

Background: Previous studies revealed that the two live vaccines, BCG and measles vaccine (MV), have beneficial non-specific effects (NSEs) reducing morbidity and mortality more than could be explained by prevention of tuberculosis and measles infection. Since live oral polio vaccine (OPV) is stopped and replaced with inactivated polio vaccine (IPV) in high-income countries and will be stopped globally after polio eradication, we undertook a review of potential NSEs of OPV on mortality. Methods: We searched PubMed for all studies of OPV and death/mortality. In low-income settings, OPV has been provided in three different settings: First, as co-administration of OPV and diphtheria-tetanus-pertussis (DTP) vaccine in three doses from 6 weeks of age. Second, as an early dose at birth (OPV0), often administered together with BCG. Third, in OPV campaigns to eradicate polio infection. We calculated relative risk (RR) of mortality for different combinations of vaccinations and RR of the mortality rate before and after OPV campaigns. Results: The majority of studies was from Guinea-Bissau. First, in three natural experiments, where DTP was missing, OPV-only compared with DTP+OPV co-administered was associated with 3-fold lower mortality rate in two community studies (RR=0.33 (0.14-0.77)) and in a hospital case fatality study (RR=0.29 (0.11-0.77)). Conversely, when OPV was missing, DTP-only was associated with 3-fold higher mortality than co-administration of DTP+OPV (RR=3.23 (1.27-8.21)). Second, in two randomised controlled trials (RCTs), OPV0 vs. no OPV0 was associated with 32% lower infant mortality. The beneficial effects of OPV0 were stronger the earlier the vaccine had been given. Third, in six population-based studies from urban and rural Guinea-Bissau, Burkina Faso and Bangladesh, the mortality rate was lower with a RR=0.75 (0.69-0.82) after OPV campaigns than before OPV campaigns. Furthermore, OPV campaigns changed the mortality effect of health interventions in nine RCTs. The intervention had the strongest beneficial effect before OPV campaigns in all RCTs; hence, OPV campaigns reduced the mortality rate and the difference between randomisation groups disappeared. Interpretation: There have been no polio cases in Guinea-Bissau in this century and no confounding factors or bias would be able to explain these patterns. The only interpretation consistent with all data is that OPV has beneficial NSEs, reducing child mortality. Child mortality may increase again once OPV is removed or replaced with IPV. If no counter-measures are taken, eradicating polio and stopping OPV may become a Pyrrhic victory. Funding: The work on non-specific effects of vaccines has been supported by the Danish Council for Development Research, Ministry of Foreign Affairs, Denmark [grant number 104.Dan.8.f.], Novo Nordisk Foundation and European Union FP7 support for OPTIMUNISE (grant: Health-F3- 2011-261375). CSB held a starting grant from the ERC (ERC-2009-StG-243149). CVIVA was supported by a grant from the Danish National Research Foundation (DNRF108). PA held a research professorship grant from the Novo Nordisk Foundation. Declaration of Interest: Nothing to declare.

Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines

Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.

Relationship Between Vaccination Status and Biopsychosocial Characteristics in Sheltered Adolescents.

IntroductionHomeless youth are a vulnerable population. A volunteer clinic supported by medical students in northeastern Pennsylvania provides shelter and healthcare to adolescents seeking refuge. We set out to determine the immunization status of youth in the shelter and evaluate for associations of immunization deficiency with demographics or biopsychosocial factors.MethodsAfter IRB approval, a retrospective cohort study was performed from existing clinical records at the shelter 2/2015-9/2019. Chart abstraction included variables such as demographics (including age, sex, and race/ethnicity), biopsychosocial factors (including childhood trauma/abuse history, substance abuse history, and sexual activity), and immunization history.ResultsA total of 440 charts were analyzed. When comparing demographics of patients that had complete vaccine regimens versus those who did not, the race was statistically significant (p=.006). The most prominent difference in race was seen for Black/African American patients; only 19.57% had a completed vaccine regimen documented. Regarding immunization history, vaccine schedules of hepatitis B, measles mumps rubella (MMR), inactivated polio vaccine (IPV), and varicella were most likely to be complete; pneumococcal conjugate vaccine (PCV) 13, rotavirus, influenza, and human papillomavirus vaccine (HPV) were least likely. There was no association found between a completed vaccine regimen and biopsychosocial variables. A larger portion of females (37.35%) completed the HPV vaccine compared to males (23.14%) (p=.009).ConclusionsIn this single-site study, this vulnerable, at-risk population of sheltered adolescents lacked the vaccinations recommended by the Centers for Disease Control and Prevention. Racial disparities further compounded this vulnerability for Black/African American teens. Additionally, a significantly greater number of female patients received the HPV vaccine compared to males.

An experience of mass administration of fractional dose inactivated polio vaccine through intradermal needle-free injectors in Karachi, Sindh,\xa0Pakistan

BackgroundInactivated Polio Vaccine (IPV) campaign was conducted in February 2019 in Karachi where needle-free injectors were introduced for the administration of the fractional dose of IPV (fIPV) on a large scale. This study aimed to determine the impact of needle-free injectors on vaccination coverage.MethodsIn four towns of Karachi, fIPV was given using needle-free injectors “PharmaJet Tropis ID”. Whereas, in six towns full dose of IPV was administered to children of 4–59 months of age. Cluster surveys through rapid convenience assessment method were conducted after the completion of vaccination activity.ResultsA total of 33,815 households’ data was analyzed. Among these, 27,650 (82.8%) children were vaccinated. In fIPV areas, 85.3% of children were vaccinated compared to 79.5% in full dose IPV areas. A comparison of reasons for unvaccinated showed that 1.6% of parents do not give importance to vaccination in fIPV areas compared to 4.2% in full IPV areas (p-value < 0.0001). More children were not vaccinated due to fear of injection 1.8% in full IPV areas compared to 0.7% in fIPV areas (p-value < 0.0001). The source of campaign information shows that more frequent mobile miking 3.1% was observed in fIPV areas compared to 0.4% in full IPV areas (p-value < 0.0001).ConclusionsOur analysis supports the fractional dose of IPV in mass campaigns to achieve good vaccination coverage especially using needle-free injectors “PharmaJet Tropis ID” and vigorous social mobilization activities are expedient in accomplishing high coverage.

The Pathology of Poliomyelitis and the Vaccines and Nonvaccine Therapy

Poliomyelitis is an exclusively human disease that mainly affects children. Clinical features of poliomyelitis can be varied, from mild illness to the most severe paralysis, and the factor why poliomyelitis has different performances in individuals has been proved strongly correlated with membrane protein CD155. The nervous system shows a special protecting phenomenon against the invasion of poliovirus, and the mechanism is not very clear at present. Vaccines are the main means of preventing and controlling polio, and many different vaccines have been invented in the process of fighting polio. Inactivated polio vaccine (IPV) and oral polio vaccine (OPV) are the two main vaccines. IPV is known for its safety while OPV is widely used in developing countries because of its relatively low cost. This usage also leads to some side effects: vaccine-associated paralytic polio (VAPP) and vaccine-derived poliovirus (VDPV). Now, for polio eradication, the elimination of these two diseases has become particularly important. Thus, a new type of vaccine was created: sequential IPV-OPV with the safety of IPV and the low cost of OPV. This paper will talk about the different polio vaccines and their effects. An enormous difference between people who have gotten the vaccine and people who have not got the vaccine. Comparing the two kinds of people, people who get normal poliovirus, and people who get poliovirus after taking a vaccine, known as VAPP (vaccine-associated paralytic poliomyelitis), the former cannot get full recovery whole life and the latter has a very low possibility. In conclusion, people should take vaccines if it is affordable for them.

Подбор сорбента для очистки концентрата вакцинного штамма полиовируса методом гель-фильтрации

In the production of anti-virus vaccines, the replacement of wild-type with attenuated strains is becoming relevant. Sabin strains are the most suitable candidates for this replacement in the production of inactivated poliovirus vaccines. The main problem in the development of methods for purification of viral particles of Sabin strains is the preservation of their stability and antigenic properties. We have compared the sorbents used for gel-filtration of poliovirus concentrates and have selected a chromatographic resin, Sephacryl S-300HR, which provides a high yield of the target product and its high purity both during cultivation in roller bottles and in bioreactors. It was also shown that, along with effective purification, Sephacryl S-300HR allows preservation of the polyovirus antigenic properties and can be used in the preparation of monovalent inactivated poliovirus concentrates that meet the good quality requirements. inactivated polio vaccine (IPV), oral polio vaccine (OPV), poliomyelitis, chromatographic purification, gel filtration The authors grateful to L.P. Antonova and A.A. Butusova for their assistance in conducting the research.

PREVALENCE OF NEUTRALIZING ANTIBODIES AGAINST POLIOVIRUS 1, 2, AND 3 IN HEALTHCARE PROFESSIONALS AGED 20-50 YEARS.

ABSTRACTObjective: To describe the prevalence of neutralizing antibodies against poliovirus (PV1, PV2, and PV3) in blood samples of healthcare professionals aged 20 to 50 years.Methods: Health professionals who serve children at Darcy Vargas Children’s Hospital and the Department of Pediatrics of Irmandade da Santa Casa de São Paulo. The sample size was calculated at 323 participants. The Mantel-Haenszel chi-square was used to verify differences between groups. The neutralization reaction detected human poliovirus antibodies. For susceptible individuals, vaccination with the inactivated+triple acellular polio vaccine was performed, and neutralizing antibodies were re-dosed after one week.Results: 333 professionals were studied - 92.8% were immune to poliovirus 1, 86.5% to poliovirus 2, and 63.3% to poliovirus 3; 37% had titers less than 1:8 for any serotype, 5;1% had titers below 1:8 for all three. Vaccination with inactivated polio vaccine was performed for susceptible participants, and neutralizing antibodies were dosed after one week, showing increased titers for all polioviruses.Conclusions: Despite the detection of a significant percentage of individuals with low poliovirus antibody titer, the challenge with vaccination demonstrated immune response compatible with poliovirus immunity.

Immune Response of Gamma-Irradiated Inactivated Bivalent Polio Vaccine Prepared plus Trehalose as a Protein Stabilizer in a Mouse Model

Introduction: Poliovirus causes paralysis by infecting the nervous system. Currently, 2 types of polio vaccine are given in many countries in polio eradication program including inactivated polio vaccine (IPV) and oral polio vaccine (OPV). Because of OPV-related paralysis, OPV should be replaced by IPV. Methods: The aim of this study was to prepare the gamma-irradiated IPV and determine its effectiveness compared with the commercial vaccine (OPV) in the mouse model. The virus titration of OPV was determined and then inactivated by the appropriate dose of gamma radiation into an irradiated vaccine formula. The vaccine was inoculated in BALB/c mice in 2 different formulations of intramuscular injection with 2-week intervals. The level of anti-polio-neutralizing antibody and polio-specific splenocyte proliferation assay were evaluated by collecting the blood samples and spleens of the vaccinated groups with conventional vaccine and irradiated vaccine. Results: There was a significant increase in the neutralizing antibody titration between all of the vaccinated groups and negative control group (A) (p < 0.05). And it shows that the IPV by gamma irradiation has the highest antibody titration. Also, the increasing of stimulation index value in the B* group, F group, and G group was the most against other groups. Furthermore, the neutralizing anti-serum titer and splenic lymphocyte proliferation assay show humoral and cellular immunity were significantly increased in the irradiated vaccine group as compared with conventional group. Conclusion: According to the results, gamma-irradiated IPV could induce humoral and cellular immunity in vaccinated mouse groups, so the irradiated poliovirus could be recommended as a good candidate vaccine to prevent the transport of poliovirus to the central nervous system and thus protect against paralysis.

Status of India’s immunization programme: Achieving goals of global vaccine action plan

In May 2012, World Health Assembly approved the Global Vaccine Action Plan (GVAP). The aim of GVAP is to achieve the Decade of Vaccines vision by delivering universal access to immunization. The mission of GVAP is to improve health by 2020 by extending full benefits of immunization to all people all over the world. Various indicators assessing the progress of the countries’ immunization program are available on the GVAP portal along with annual data of these countries. The immunization programs of the countries can be evaluated and compared based on these indicators. Immunization programme of India is one of the largest programme in the world and caters to a birth cohort of 2.6 million. In last decade, new vaccines like Pentavalent, Inactivated Polio Vaccine (IPV), Pneumococcal Conjugated Vaccine (PCV), Measles & Rubella vaccine and rotavirus vaccine have been introduced along with new technology like electronic vaccine intelligence network (eVIN) to monitor the vaccine logistics. National Technical Advisory Group on Immunization (NTAGI) and Adverse Effect following Immunization (AEFI) surveillance establishment in India has further strengthened the program. The Universal Immunization Programme of India is moving in a direction that is consistent with the perspective of the global vaccine action plan (GVAP) making it possible for the country to achieve most of the targets laid down by GVAP by 2020. Keywords: Global Vaccine Action Plan, Immunization, UIP, NTAGI, AEFI

Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, in primary and booster trials in Asia, Central America and Europe

Background: Withdrawal of OPV and the widespread introduction of IPV is key in the Polio Endgame Strategy. This transition from OPV to IPV requires more and affordable IPV in quantities sufficient to secure at least two doses of IPV for every child. An adjuvanted inactivated polio vaccine (IPV-Al), obtained by adsorption of a reduced dose of inactivated poliovirus to an aluminium hydroxide adjuvant, can help mitigate global supply and cost constraints of IPV through dose-sparing. Aim: Investigation of immunogenicity and safety of IPV-Al compared to standard IPV: Methods and materials: Two primary vaccination phase 3 trials in infants vaccinated at 6, 10, 14 weeks and 9 months in the Philippines; at 2, 4, 6 months and 15–18 months in Panama. A Phase 2 primary vaccination trial in the Dominican Republic in infants vaccinated at 6, 10, 14 weeks. A Phase 1/2 booster vaccination trial in Denmark in children and adolescents (10–15 years) with a history of standard IPV vaccination. Results: Seroconversion rates (an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8) evaluated one month after primary vaccination were: polio type 1, 96–98% (IPV-Al) versus 99–100% (IPV); type 2, 94–100% versus 99–100%; and type 3, 98–99% versus 99–100%. Non-inferiority of IPV-Al to IPV (predefined 10%-point margin) was confirmed in trials assessing primary immunogenicity. In infants, robust booster responses were demonstrated following a fourth polio vaccination and post-booster geometric mean titres (GMTs) were higher than post-priming GMTs. In the adolescent trial, robust booster responses were demonstrated following a fifth polio vaccination. IPV-Al was well tolerated with a safety profile comparable to that of standard IPV in the three trials. Conclusion: IPV-Al was demonstrated to be non-inferior to standard IPV for seroconversion following primary vaccination in the EPI schedule in Philippines and Dominican Republic, and at 2, 4, 6 months in Panama. Robust post-booster responses in 9-month-olds, 15–18-month-olds and 10–15-year-olds were demonstrated for IPV-Al. IPV-Al was safe and well tolerated. Results support the applicability of the dose-sparing adjuvanted IPV-Al vaccine to help secure a more affordable and stable supply of IPV for prevention of poliomyelitis as part of the global polio eradication initiative.

Safety and immunogenicity of co-administration of meningococcal type A and measles–rubella vaccines with typhoid conjugate vaccine in children aged 15–23 months in Burkina Faso

ObjectivesThe World Health Organization pre-qualified single-dose typhoid conjugate vaccine (TCV) and requested data on co-administration with routine vaccines. The co-administration of Typbar TCV (Bharat Biotech International) with routine group A meningococcal conjugate vaccine (MCV-A) and measles–rubella (MR) vaccine was tested. MethodsThis was a double-blind, randomized controlled trial performed in Ouagadougou, Burkina Faso. Children were recruited at the 15-month vaccination visit and were assigned randomly (1:1:1) to three groups. Group 1 children received TCV plus control vaccine (inactivated polio vaccine) and MCV-A 28 days later; group 2 children received TCV and MCV-A; group 3 children received MCV-A and control vaccine. Routine MR vaccine was administered to all participants. Safety was assessed at 0, 3, and 7 days after immunization, and unsolicited adverse events and serious adverse events were assessed for 28 days and 6 months after immunization, respectively. ResultsA total of 150 children were recruited and vaccinated. Solicited symptoms were infrequent and similar for TCV and control recipients, as were adverse events (group 1, 61.2%; group 2, 64.0%; group 3, 68.6%) and serious adverse events (group 1, 2.0%; group 2, 8.0%; group 3, 5.9%). TCV generated robust immunity without interference with MCV-A vaccine. ConclusionsTCV can be safely co-administered at 15 months with MCV-A without interference. This novel study on the co-administration of TCV with MCV-A provides data to support large-scale uptake in sub-Saharan Africa.

Factors associated with the utilization of inactivated polio vaccine among children aged 12 to 23 months in Kalungu District, Uganda.

Uganda officially introduced the inactivated polio vaccine (IPV) in May 2016 as part of the polio eradication strategy and integrated it into its routine immunization programme in addition to the oral polio vaccine. The current coverage stands at 60% as of July 2017. We therefore aimed to determine factors associated with the uptake of IPV among children in Kalungu District so as to inform the implementation of the vaccine policy. A community-based cross-sectional study was conducted among caregivers of 406 eligible children aged 12–23 months through multi-stage systematic sampling and a standardized semi-structured questionnaire. Nine key informant interviews were conducted through purposive selection of health care providers and members of Village Health Teams (VHTs) based on their expertize. Modified Poisson regression and thematic content analysis were used to determine factors significant to IPV uptake among children. 71% of sampled children aged 12–23 months had received IPV in Kalungu District. The survey found that being encouraged by health workers and VHTs was significant to children’s uptake of IPV (Adjusted PR 1.24, 95% CI; 1.22–3.47). Distance to the immunization point (Adjusted PR 0.32,95% CI; 0.16–0.62) and caregiver’s education level (Adjusted PR 1.16,95% CI; 1.05–2.22) were also associated with IPV uptake. Qualitative findings from health workers and VHT members further confirmed the perception that distance to the immunization post was important, and VHTs also stated that being encouraged by health workers was critical to IPV uptake. The current prevalence of IPV uptake among children aged 12–23 months in Kalungu is 71%, higher than the last reported national coverage (60%), though still below the recommended national coverage of 95%. Efforts should be focused on sensitization of caregivers through health workers and VHTs. Immunization outreach should be strengthened so as to bring services closer to patients.

In-Vitro Inactivation of Sabin-Polioviruses for Development of Safe and Effective Polio Vaccine.

After years of global collaboration; we are steps away from a polio-free world. However, the currently conventional inactivated polio vaccine (cIPV) is suboptimal for the post eradication era. cIPV production cost and biosafety hazards hinder its availability and coverage of the global demands. Production of IPV from the attenuated Sabin strains (sIPV) was an ideal solution and scientists work extensively to perfect a safe, effective and affordable sIPV. This study investigated the ability of hydrogen peroxide (H2O2), ascorbic acid (AA) and epigallocatechin-3-gallate (EGCG) as alternatives for Formaldehyde (HCHO) to inactivate Sabin-polioviruses strains for sIPV production. Sabin-polioviruses vaccine strains were individually treated with AA, EGCG or H2O2 and were compared to HCHO. This was investigated by determination of the inactivation kinetics on HEP2C cells, testing of D-antigen preservation by ELISA and the immune response in Wistar rats of the four vaccine preparations. H2O2, AA and EGCG were able to inactivate polioviruses within 24 h while HCHO required 96 h. Significant high D-antigen levels were observed using AA, EGCG and H2O2 compared to HCHO. Rat sera tested for neutralizing antibodies showed comparable results. These findings support the idea of using these inactivating agents as safe and time- saving alternatives for HCHO to produce sIPV.

Timeliness of DTaP-IPV-Hib Vaccination and Development of Atopic Dermatitis Between 4 Months and 1 Year of Age—Register-Based Cohort Study

An Australian study including 4433 children found that delayed Diphtheria-Tetanus-acellular Pertussis-containing vaccination was associated with reduced risk of developing atopic dermatitis (AD) before age 1 year. We assessed whether delayed vaccination against diphtheria, tetanus, acellular pertussis, polio, and Haemophilus influenzae type b (Diphtheria, Tetanus, acellular Pertussis - Inactivated Polio vaccine - Haemophilus influenzae type b [DTaP]) was associated with a reduced risk of new cases of AD before age 1 year in Denmark. We used nationwide registers to follow 883,160 children born in Denmark from 1997 to 2012. Binary regression models adjusting for potential confounding factors were applied to estimate relative risks (adjusted relative risks [aRRs]) of developing AD among children with delayed DTaP vaccination (defined as given 1 month or more after the recommended age) compared with timely vaccinated children. Among 143,429 children with a delayed first dose of DTaP, 4,847 (3.4%) developed AD between age 4 months and 1 year, compared with 27,628 (3.7%) among 739,731 children not having delayed DTaP (aRR 0.94; 95% CI, 0.91-0.97). The aRR was 0.94 (95% CI, 0.90-0.99) for children with a delayed second dose, and the aRR was 0.88 (95% CI, 0.82-0.93) when comparing children with delayed first and second doses with all timely vaccinated children. The results support the hypothesis that delayed vaccination with DTaP is associated with reduced risk of developing new cases of AD after age 4 months. The dose-dependent relationship strengthens the evidence of a causal relationship. Some countries are introducing maternal pertussis vaccination and delaying the first dose of DTaP, providing a possibility for further testing the hypothesis.

Immunogenicity of seasonal inactivated influenza and inactivated polio vaccines among children in Senegal: Results from a cluster-randomized trial

Data on influenza vaccine immunogenicity in children are limited from tropical developing countries. We recently reported significant, moderate effectiveness of a trivalent inactivated influenza vaccine (IIV) in a controlled, cluster-randomized trial in children in rural Senegal during 2009, a year of H3N2 vaccine mismatch (NCT00893906). We report immunogenicity of IIV3 and inactivated polio vaccine (IPV) from that trial. We evaluated hemagglutination inhibition (HAI) and polio antibody titers in response to vaccination of three age groups (6 through 35 months, 3 through 5 years, and 6 through 8 years). As all children were IIV naïve, each received two vaccine doses, although titers were assessed after only the first dose for subjects aged 6 through 8 years. Seroconversion rates (4-fold titer rise or increase from <1:10 to ≥1:40) were 74–87% for A/H1N1, 76–87% for A/H3N2, and 54–79% for B/Yamagata. Seroprotection rates (HAI titer ≥ 1:40) were 79–88% for A/H1N1, 88–96% for A/H3N2, and 52–74% for B/Yamagata. IIV responses were lowest in the youngest age group, and they were comparable between ages 3 through 5 years after two doses and 6 through 8 years after one dose. We found that baseline seropositivity (HAI titer ≥ 1:10) was an effect modifier of IIV response. Using a seroprotective titer (HAI titer ≥ 1:160) recommended for IIV evaluation in children, we found that among subjects who were seropositive at baseline, 69% achieved seroprotection for both A/H1N1 and A/H3N2, while among those who were seronegative at baseline, seroprotection was achieved in 11% for A/H1N1 and 22% for A/H3N2. The IPV group had high baseline polio antibody seropositivity and appropriate responses to vaccination. Our data emphasize the importance of a two-dose IIV3 series in vaccine naïve children. IIV and IPV vaccines were immunogenic in Senegalese children.

Polio switch strategy: An obituary in the making?

India was certified free of polio in 2014. Until now, the oral polio vaccine (OPV) was being used in India. As the OPV is a live vaccine, vaccine-associated paralytic poliomyelitis may occur after its use. The aim is to replace the OPV with injectable polio vaccine. The Polio Eradication and Endgame Strategic Plan 2013–2018 has been made to eradicate polio. A switch from the trivalent OPV (tOPV) to bivalent OPV (bOPV) has been undertaken in all countries since April 2016. tOPV vials have been withdrawn and replaced by bOPV. In addition, the inactivated polio vaccine (IPV) has been introduced. The next step would be to remove the type 3 virus component followed by complete cessation of the OPV and a final switch to the IPV. The timeline has been fixed as 2018–2019. Replacement of a vaccine may raise fears in the community that need to be addressed. Re-emergence of circulating vaccine-derived poliovirus after withdrawal of the tOPV may occur. Proper disposal of vaccine vials needs to be ensured. Proper training of vaccinators is important. All stakeholders need to be incorporated, and focus should be more on deprived populations. The switch marks a significant step towards the final goal of polio eradication. Finally, the importance of community participation cannot be overemphasized. Sustained surveillance is the key to prevent occurrence of cases in polio-free countries through importation.

Safety and Immunogenicity of Co-Administration of Meningococcal Type A and Measles Rubella Vaccines with Typhoid Conjugate Vaccine in Children Aged 15-23 Months in Burkina Faso

Background. The World Health Organization (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) in December 2017. WHO requested data on co-administration of TCV with Expanded Programme on Immunisation vaccines in typhoid-endemic countries. We tested co-administration of Typbar TCV® [Bharat Biotech International] with routine group A meningococcal conjugate vaccine (MCV-A) and measles-rubella (MR) vaccine. Methods: We conducted a double-blind, randomised, controlled trial at Schiphra Protestant Hospital outpatient paediatric clinic, Ouagadougou, Burkina Faso. Children recruited at routine 15-month vaccination visits were randomly assigned (1:1:1) to intramuscularly receive: Group 1) TCV plus control vaccine (inactivated polio vaccine) and MCV-A 28 days later; Group 2) TCV and MCV-A; or, Group 3) MCV-A and control vaccine. Routine MR vaccine was administered subcutaneously at day 0 to all participants. The primary outcome was safety, assessed by local and systemic reactions at 0, 3, and 7 days after immunisation; and unsolicited adverse events and serious adverse events 28 days and 6 months after immunisation, respectively. Primary analysis included all participants receiving at least one intramuscular vaccine. Immunogenicity was assessed as a secondary endpoint. ClinicalTrials.gov identifier NCT03614533. Findings: Between December 3, 2018 and February 18, 2019, we recruited and vaccinated 150 children: Group 1 (n=49), Group 2 (n=50), and Group 3 (n=51). Solicited local and systemic symptoms were infrequent and similar for TCV and control recipients, as were adverse events (Group 1: 61·2%, 95% CI 46·2-74·8; Group 2: 64·0%, 95% CI 49·2-77·1; Group 3: 68·6%, 95% CI 54·1-80·9) and serious adverse events (Group 1: 2·0%, 95% CI 0·1-10·9; Group 2: 8·0%, 95% CI 2·2-19·2; Group 3: 5·9%, 95% CI 1·2-16·2). No serious adverse events were related to vaccination. TCV generated robust immunity without interference with MCV-A or MR vaccine. Interpretation: TCV can be safely co-administered with routine MCV-A and MR vaccine. Trial Registration: y. The trial is registered at ClinicalTrials.gov, Identifier NCT03614533. Funding: Bill & Melinda Gates Foundation. Declaration of Interests: The authors have no competing interests to declare. Ethics Approval Statement: The study was approved by ethics committees in Burkina Faso (Comite d’Ethique pour la Recherche en Sante [CERS], Ouagadougou, Burkina Faso) and Maryland, USA (Institutional Review Board, University of Maryland, Baltimore), and by the Regulatory Authority in Burkina Faso (L’Agence Nationale de Regulation Pharmaceutique, Ouagadougou, Burkina Faso).

The second coming: The comeback of the live vaccines.

Live vaccines are gradually replaced by protein-based vaccines given the latter's better safety. But live vaccines seem to be more efficient via stimulation of the innate immune system.

Sero-survey of polio antibodies and quality of acute flaccid paralysis surveillance in Chongqing, China: A cross-sectional study.

Serums were collected from people to assess whether polio immunity level was high enough to satisfy the polio vaccine immunization switch in Chongqing.People in 7 age groups (<1 year, 1–2 years, 3–4 years, 5–6 years, 7–14 years, 15–19 years, ≧20 years) were randomly selected in 3 areas by different geographical features in 2015. Peripheral venous blood samples were obtained and assays to detect poliovirus (PV) –neutralizing antibodies were performed. Acute flaccid paralysis (AFP) data was collected from 2012 to 2016 in Chongqing to evaluate the performance of AFP surveillance system by indicator analysis.A total of 636 people were tested for PV neutralization antibodies (NA). Overall NA seroprevalence for PV1, PV2 and PV3 were 93.40%, 96.38% and 91.82%, and geometric mean titers (GMTs) were 61.14, 66.78 and 21.47, respectively. GMTs and NA seroprevalence for PV1, PV2 and PV3 in older people were lower than young people. There were significant differences in seroprevalences of PV1 and PV3 among geographic areas (P < .05) in Chongqing.High seroprevalence for PV1, PV2, and PV3 and qualified capability for monitoring AFP cases showed that the polio eradication program has made positive achievements in Chongqing and established a stable base for a polio vaccine immunization switch. Nevertheless, GMTs were negatively associated with age in the geographic districts with poor economical features, which will increase the risk of emergence of vaccine-derived PV after polio vaccine switch. More than 1 dose of inactivated polio vaccine should be introduced into the polio vaccine schedule, and the supplementary immunization of polio should still be annually carried out after polio vaccine switch, especially among elder children and the adults.