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Background Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection. Conclusions Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, su, Background: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods: In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results: Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05-7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09-1.57) and BA.3 (1.32, 1.09-1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76-0.98), BA.4 (0.85, 0.75-0.97), and BA.5 (0.87, 0.76-0.99) antigens in individuals with a prior infection. Conclusions: Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of O

Background Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection. Conclusions Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, su, Background: Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods: In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results: Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05-7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09-1.57) and BA.3 (1.32, 1.09-1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76-0.98), BA.4 (0.85, 0.75-0.97), and BA.5 (0.87, 0.76-0.99) antigens in individuals with a prior infection. Conclusions: Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of O

Vaccine hesitancy became a more and more important issue during the COVID-19 pandemic. Due to the emergence of new variants, many international health agencies have already begun administering booster doses of the vaccine in response to these threats. Studies have emphasized the effectiveness of different types of incentive-based strategies to increase vaccination behaviors. The purpose of the present study was to identify the correlation between different types of incentives (legal or financial) with people's intentions to get a COVID-19 booster vaccine. We conducted a cross-sectional study between 29 January 2022 and 03 February 2022. An online quantitative survey was carried out in Italy. One thousand and twenty-two Italian adults were recruited by a professional panel provider. Descriptive statistics were computed for the five variables concerning the incentives (monetary, tax, fee, health certification, travel) toward vaccination. A general linear model (GLM) was then computed to compare the scores of the five different variables within the subjects. The general linear model showed a significant within-subjects main effect. Post-hoc comparisons showed that among the financial incentive, the monetary reward is rated lower than all the others. Tax and fees both resulted lower than both the legal incentives. Finally, COVID-19 health certification and travel did not result significantly different from each other. This study offers an important contribution to public policy literature and to policymakers in their efforts to explain and steer booster vaccination acceptance while facing an ongoing pandemic.

Coronavirus Disease 2019 (COVID-19) adalah penyakit menular yang disebabkan oleh Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) yang berlangsung cukup cepat dan menyebar ke berbagai negara dalam waktu singkat. Vaksinasi merupakan salah satu upaya menanggulangi pandemi COVID-19. Salah satu jenis vaksin yang saat ini digunakan adalah vaksin dengan jenis inaktivasi. Tujuan penelitian ini untuk mengetahui kadar antibodi setelah vaksinasi kedua menggunakan jenis vaksin inaktivasi sebelum diberikan vaksinasi lanjutan ketiga, dan faktor-faktor yang mempengaruhinya. Penelitian menggunakan metode observasional yang berlokasi di Poltekkes Kemenkes Jakarta III selama Februari 2022, jumlah sampel sebanyak 33 orang. Pengukuran kadar antibodi S-RBD (receptor binding domain) SARS-CoV-2 kuantitatif menggunakan metode ECLIA dengan alat Cobas e-411. Setelah penelitian, kadar antibodi 100% reaktif dengan rentang yang bervariasi, kelompok tinggi (>250 U/mL) sebanyak 84,8%, menengah (117-250 U/mL) sebanyak 6,1%, dan rendah (<117 U/mL) sebanyak 9,1%. Terdapat hubungan antara indeks massa tubuh dengan kadar antibodi (p=0,046). Tidak terdapat hubungan antara jenis kelamin, usia, jarak waktu setelah vaksin kedua, riwayat COVID-19, dan riwayat komorbid dengan kadar antibodi. Vaksin COVID-19 jenis inaktivasi menginduksi respons antibodi kuat yang masih bertahan sebelum dilakukannya vaksinasi lanjutan ketiga., Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which progresses quite quickly and spreads to various countries in a short time. Vaccination is one of the efforts to tackle the COVID-19 pandemic. One type of vaccine that is currently used is a vaccine with a type of virus inactivation. The purpose of this study was to determine antibody levels after the second vaccination using a type of virus inactivation vaccine before being given the third follow-up vaccination, and the factors that influence it. The research used an observational method located at the Jakarta III Ministry of Health Poltekkes during February 2022, the number of samples was 33 people. Quantitative measurement of SARS-CoV-2 S-RBD (receptor binding domain) antibody levels used the ECLIA method with the Cobas e-411 tool. After the study, the antibody levels were 100% reactive with varying ranges, the high group (> 250 U/mL) was 84.8%, the medium (117-250 U/mL) was 6.1%, and the low (<117 U/mL) mL) as much as 9.1%. There is a relationship between body mass index and antibody levels (p=0.046). There is no relationship between gender, age, time interval after the second vaccine, history of COVID-19, and history of comorbidities with antibody levels. The virus-inactivated COVID-19 vaccine induces a strong antibody response that persists before the third follow-up vaccination.

Summary Background COVID-19 booster vaccine uptake rates are behind the rate of primary vaccination in many countries. Governments and non-governmental institutions rely on a range of interventions aiming to increase booster uptake. Yet, little is known how experts and the general public evaluate these interventions. Methods We applied a novel crowdsourcing approach to provide rapid insights on the most promising interventions to promote uptake of COVID-19 booster vaccines. In the first phase (December 2021), international experts (n = 78 from 17 countries) proposed 46 unique interventions. To reduce noise and potential bias, in the second phase (January 2022), experts (n = 307 from 34 countries) and representative general population samples from the UK (n = 299) and the US (n = 300) rated the proposed interventions on several evaluation criteria, including effectiveness and acceptability, on a 5-point Likert-type scale. Findings Sanctions were evaluated as potentially most effective but least accepted. Evaluations by expert and general population samples were considerably aligned. Interventions that received the most positive evaluations regarding both effectiveness and acceptability across evaluation groups were: a day off work after getting vaccinated, financial incentives, tax benefits, promotional campaigns, and mobile vaccination teams. Interpretation The results provide useful insights to help governmental and non-governmental institutions in their decisions about which interventions to implement. Additionally, the applied crowdsourcing method may be used in future studies to retrieve rapid insights on the comparative evaluation of (health) policies. Funding This study received funding from the Austrian Science Fund (SFB F63) and the University of Vienna.

Summary Background COVID-19 booster vaccine uptake rates are behind the rate of primary vaccination in many countries. Governments and non-governmental institutions rely on a range of interventions aiming to increase booster uptake. Yet, little is known how experts and the general public evaluate these interventions. Methods We applied a novel crowdsourcing approach to provide rapid insights on the most promising interventions to promote uptake of COVID-19 booster vaccines. In the first phase (December 2021), international experts (n = 78 from 17 countries) proposed 46 unique interventions. To reduce noise and potential bias, in the second phase (January 2022), experts (n = 307 from 34 countries) and representative general population samples from the UK (n = 299) and the US (n = 300) rated the proposed interventions on several evaluation criteria, including effectiveness and acceptability, on a 5-point Likert-type scale. Findings Sanctions were evaluated as potentially most effective but least accepted. Evaluations by expert and general population samples were considerably aligned. Interventions that received the most positive evaluations regarding both effectiveness and acceptability across evaluation groups were: a day off work after getting vaccinated, financial incentives, tax benefits, promotional campaigns, and mobile vaccination teams. Interpretation The results provide useful insights to help governmental and non-governmental institutions in their decisions about which interventions to implement. Additionally, the applied crowdsourcing method may be used in future studies to retrieve rapid insights on the comparative evaluation of (health) policies. Funding This study received funding from the Austrian Science Fund (SFB F63) and the University of Vienna.

To advance research and development of improved pertussis vaccines, new immunoassays are needed to qualify the outcome of Bordetella pertussis (Bp) specific CD4+ T-cell differentiation. Here, we applied a recently developed whole blood assay to evaluate Bp specific CD4+ T-cell responses. The assay is based on intracellular cytokine detection after overnight in vitro Bp antigen stimulation of diluted whole blood. We show for the first time that CD4+ T-cell memory of Th1, Th2, and Th17 lineages can be identified simultaneously in whole blood. Participants ranging from 7 to 70 years of age with different priming backgrounds of whole-cell pertussis (wP) and acellular pertussis (aP) vaccination were analyzed around an acellular booster vaccination. The assay allowed detection of low frequent antigen-specific CD4+ T-cells and revealed significantly elevated numbers of activated and cytokine-producing CD4+ T-cells, with a significant tendency to segregate recall responses based on primary vaccination background. A stronger Th2 response hallmarked an aP primed cohort compared to a wP primed cohort. In conclusion, analysis of Bp specific CD4+ T-cell responses in whole blood showed separation based on vaccination background and provides a promising tool to assess the quantity and quality of CD4+ T-cell responses induced by vaccine candidates., SCOPUS: ar.j, info:eu-repo/semantics/published

The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac(®) vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa(®) (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

RIVM rapport:In deze veldproef is de immunogeniteit en de reactogeniteit van 3 verschillende ACVAs en WCV van het RIVM onderzocht, gecombineerd met DTP toegediend als booster bij 4-jarige kinderen. Bij deze kinderen is tevens de immuunrespons op IPVvero (geproduceerd op Vero cellen) vergeleken met het reguliere IPV-MK (geproduceerd op MK cellen). De kinderen in deze studie zijn eerder gevaccineerd met 4 doses DKTP van het RIVM op de leeftijd van 3, 4, 5 en 11 maanden. De ACVAs bevatten PT en FHA (ACV-PM), met PRN als derde component (ACV-SB) en FIM als vierde component (AVC-WL). Het was een open, gerandomiseerde, gecontroleerde studie met geblindeerde serologische bepalingen. Samenvattend geeft deze studie aan dat een toevoeging van een pertussis vaccinatie op 4-jarige leeftijd zinvol kan zijn bij een epidemische verheffing, waarbij de voorkeur uitgaat naar een combinatievaccin met een ACV- of een WCV-component vanwege de enkelvoudige toediening. Het IPVvero blijkt een zeer immunogeen vaccin te zijn en op zijn minst gelijkwaardig aan het huidige IPV-MK., In this trial we studied the immunogenicity and reactogenicity of three different ACVAs and the RIVM-WCV combined with DT-IPV, administered as a booster in children four years of age. In these children, the immune response of IPV vero (produced on Vero cells) was also evaluated, together with the regular IPV-MK (produced on MK cells). The children in this study were immunized three years earlier with four doses of the RIVM DTP-IPV at the ages of 3, 4, 5 and 11 months. The ACVAs were composed of PT and FHA (2 components of ACV-PM), PT, FHA and PRN (3 components of ACV-SB) and PT, FHA, PRN and FIM (4 components of ACV-WL). The study was an open, randomized, controlled study with a blinded serological evaluation. All the responses to the different vaccine components clearly demonstrate that the children were well primed with the DTP-IPV. In conclusion, this study demonstrates that an addition of a pertussis vaccination in four year-old children could be useful in an epidemical situation, in which a combination vaccine with an ACV- or a WCV-component requiring a single administration is preferred. IPV vero is shown to be a very immunogenic vaccine and at least similar to the regular IPV-MK.

In deze veldproef is de immunogeniteit en de reactogeniteit van 3 verschillende ACVAs en WCV van het RIVM onderzocht, gecombineerd met DTP toegediend als booster bij 4-jarige kinderen. Bij deze kinderen is tevens de immuunrespons op IPVvero (geproduceerd op Vero cellen) vergeleken met het reguliere IPV-MK (geproduceerd op MK cellen). De kinderen in deze studie zijn eerder gevaccineerd met 4 doses DKTP van het RIVM op de leeftijd van 3, 4, 5 en 11 maanden. De ACVAs bevatten PT en FHA (ACV-PM), met PRN als derde component (ACV-SB) en FIM als vierde component (AVC-WL). Het was een open, gerandomiseerde, gecontroleerde studie met geblindeerde serologische bepalingen. Samenvattend geeft deze studie aan dat een toevoeging van een pertussis vaccinatie op 4-jarige leeftijd zinvol kan zijn bij een epidemische verheffing, waarbij de voorkeur uitgaat naar een combinatievaccin met een ACV- of een WCV-component vanwege de enkelvoudige toediening. Het IPVvero blijkt een zeer immunogeen vaccin te zijn en op zijn minst gelijkwaardig aan het huidige IPV-MK., In this trial we studied the immunogenicity and reactogenicity of three different ACVAs and the RIVM-WCV combined with DT-IPV, administered as a booster in children four years of age. In these children, the immune response of IPV vero (produced on Vero cells) was also evaluated, together with the regular IPV-MK (produced on MK cells). The children in this study were immunized three years earlier with four doses of the RIVM DTP-IPV at the ages of 3, 4, 5 and 11 months. The ACVAs were composed of PT and FHA (2 components of ACV-PM), PT, FHA and PRN (3 components of ACV-SB) and PT, FHA, PRN and FIM (4 components of ACV-WL). The study was an open, randomized, controlled study with a blinded serological evaluation. All the responses to the different vaccine components clearly demonstrate that the children were well primed with the DTP-IPV. In conclusion, this study demonstrates that an addition of a pertussis vaccination in four year-old children could be useful in an epidemical situation, in which a combination vaccine with an ACV- or a WCV-component requiring a single administration is preferred. IPV vero is shown to be a very immunogenic vaccine and at least similar to the regular IPV-MK.

RIVM rapport:In deze veldproef is de immunogeniteit en de reactogeniteit van 3 verschillende ACVAs en WCV van het RIVM onderzocht, gecombineerd met DTP toegediend als booster bij 4-jarige kinderen. Bij deze kinderen is tevens de immuunrespons op IPVvero (geproduceerd op Vero cellen) vergeleken met het reguliere IPV-MK (geproduceerd op MK cellen). De kinderen in deze studie zijn eerder gevaccineerd met 4 doses DKTP van het RIVM op de leeftijd van 3, 4, 5 en 11 maanden. De ACVAs bevatten PT en FHA (ACV-PM), met PRN als derde component (ACV-SB) en FIM als vierde component (AVC-WL). Het was een open, gerandomiseerde, gecontroleerde studie met geblindeerde serologische bepalingen. Samenvattend geeft deze studie aan dat een toevoeging van een pertussis vaccinatie op 4-jarige leeftijd zinvol kan zijn bij een epidemische verheffing, waarbij de voorkeur uitgaat naar een combinatievaccin met een ACV- of een WCV-component vanwege de enkelvoudige toediening. Het IPVvero blijkt een zeer immunogeen vaccin te zijn en op zijn minst gelijkwaardig aan het huidige IPV-MK., In this trial we studied the immunogenicity and reactogenicity of three different ACVAs and the RIVM-WCV combined with DT-IPV, administered as a booster in children four years of age. In these children, the immune response of IPV vero (produced on Vero cells) was also evaluated, together with the regular IPV-MK (produced on MK cells). The children in this study were immunized three years earlier with four doses of the RIVM DTP-IPV at the ages of 3, 4, 5 and 11 months. The ACVAs were composed of PT and FHA (2 components of ACV-PM), PT, FHA and PRN (3 components of ACV-SB) and PT, FHA, PRN and FIM (4 components of ACV-WL). The study was an open, randomized, controlled study with a blinded serological evaluation. All the responses to the different vaccine components clearly demonstrate that the children were well primed with the DTP-IPV. In conclusion, this study demonstrates that an addition of a pertussis vaccination in four year-old children could be useful in an epidemical situation, in which a combination vaccine with an ACV- or a WCV-component requiring a single administration is preferred. IPV vero is shown to be a very immunogenic vaccine and at least similar to the regular IPV-MK.

RIVM rapport:In deze veldproef is de immunogeniteit en de reactogeniteit van 3 verschillende ACVAs en WCV van het RIVM onderzocht, gecombineerd met DTP toegediend als booster bij 4-jarige kinderen. Bij deze kinderen is tevens de immuunrespons op IPVvero (geproduceerd op Vero cellen) vergeleken met het reguliere IPV-MK (geproduceerd op MK cellen). De kinderen in deze studie zijn eerder gevaccineerd met 4 doses DKTP van het RIVM op de leeftijd van 3, 4, 5 en 11 maanden. De ACVAs bevatten PT en FHA (ACV-PM), met PRN als derde component (ACV-SB) en FIM als vierde component (AVC-WL). Het was een open, gerandomiseerde, gecontroleerde studie met geblindeerde serologische bepalingen. Samenvattend geeft deze studie aan dat een toevoeging van een pertussis vaccinatie op 4-jarige leeftijd zinvol kan zijn bij een epidemische verheffing, waarbij de voorkeur uitgaat naar een combinatievaccin met een ACV- of een WCV-component vanwege de enkelvoudige toediening. Het IPVvero blijkt een zeer immunogeen vaccin te zijn en op zijn minst gelijkwaardig aan het huidige IPV-MK., In this trial we studied the immunogenicity and reactogenicity of three different ACVAs and the RIVM-WCV combined with DT-IPV, administered as a booster in children four years of age. In these children, the immune response of IPV vero (produced on Vero cells) was also evaluated, together with the regular IPV-MK (produced on MK cells). The children in this study were immunized three years earlier with four doses of the RIVM DTP-IPV at the ages of 3, 4, 5 and 11 months. The ACVAs were composed of PT and FHA (2 components of ACV-PM), PT, FHA and PRN (3 components of ACV-SB) and PT, FHA, PRN and FIM (4 components of ACV-WL). The study was an open, randomized, controlled study with a blinded serological evaluation. All the responses to the different vaccine components clearly demonstrate that the children were well primed with the DTP-IPV. In conclusion, this study demonstrates that an addition of a pertussis vaccination in four year-old children could be useful in an epidemical situation, in which a combination vaccine with an ACV- or a WCV-component requiring a single administration is preferred. IPV vero is shown to be a very immunogenic vaccine and at least similar to the regular IPV-MK.