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In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

\"By the end of the 1950s Hungary became an unlikely leader in what we now call global health. Only three years after Soviet tanks crushed the revolution of 1956, Hungary became one of the first countries to introduce the Sabin vaccine into its national vaccination programme\"-- Provided by publisher.

Combination vaccines are effective in simplifying complex vaccination schedules involving multiple vaccines. A fully liquid hexavalent diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)- hepatitis B (HepB)-inactivated poliovirus (IPV)-Haemophilus influenzae b (Hib) vaccine (HEXASIIL®), manufactured by Serum Institute of India Pvt. Ltd. was tested for safety and immunogenicity following booster vaccination. This was a phase-II/III, open label, multicentric, controlled trial in toddlers (phase II) and infants (phase III) in India. This manuscript presents results of phase II. Healthy toddlers aged 12–24 months were randomized (1:1) to receive a 0.5 ml booster dose of HEXASIIL® or comparator Pentavac SD + Poliovac, intramuscularly and followed for 28 days for safety assessment. Blood samples were collected pre-vaccination and 28 days post-vaccination to assess immunogenicity. Descriptive summary statistics were provided for safety and immunogenecity analyses. A total of 223 subjects were randomized. One subject droped out prior to dosing, due to consent withdrawal. Thus, 222 subjects received study vaccine (110 HEXASIIL® and 112 comparator). Frequency of solicited adverse events was comparable between HEXASIIL® and comparator (85.5 % vs 90.2 %). Most local and systemic solicited AEs were mild to moderate in severity. All events resolved completely without any sequelae and none led to subject discontinuation. No vaccine related serious AE was reported. Post vaccination, seroprotection rates against tetanus, Hib and polio type 1 and 3 were 100 % in both the groups. Seroprotection rates for diphtheria (99.1 % vs 100 %) and polio type 2 (98.2 % vs 100 %) were observed in HEXASIIL® and comparator group, respectively. For Hepatitis B, seroprotection was >99 % in both groups. Seroconversion observed for Bordetella Pertussis (94.5 % vs 95.4 %) and Pertussis Toxin (77.1 % vs 87.2 %) in HEXASIIL® and comparator group, respectively. HEXASIIL® vaccine was found to be safe and immunogenic in toddlers and supported its further clinical development in infants. Clinical Trial Registration – CTRI/2019/11/022052. •Combination vaccines simplify vaccination schedules and improve compliance.•HEXASIIL® vaccine was compared to licensed DTwP-HepB-Hib + IPV vaccines.•HEXASIIL® had good safety and immunogenicity profile.•The data supported further evaluation of HEXASIIL® in infants.

This is the story of a race - not against other vaccines or other scientists, but against a deadly and devastating virus. On 1 January 2020, Sarah Gilbert, Professor of Vaccinology at Oxford University, read an article about four people in China with a strange pneumonia. Within two weeks, she and her team had designed a vaccine against a pathogen that no one had ever seen before. Less than 12 months later, vaccination was rolled out across the world to save millions of lives from Covid-19. In Vaxxers, we hear directly from Professor Gilbert and her colleague Dr Catherine Green as they reveal the inside story of making the Oxford AstraZeneca vaccine and the cutting-edge science and sheer hard work behind it. This is their story of fighting a pandemic as ordinary people in extraordinary circumstances. Sarah and Cath share the heart-stopping moments in the eye of the storm; they separate fact from fiction; they explain how they made a highly effective vaccine in record time with the eyes of the world watching; and they give us hope for the future. Vaxxers invites us into the lab to find out how science will save us from this pandemic, and how we can prepare for the inevitable next one.

A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India. In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate – pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was >10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was >0.5. A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19]. BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer–BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8–12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.

•DTaP-IPV-HB-PRP-T immunogenicity is similar when given concomitantly with a meningococcal C conjugate vaccine or alone.•The safety profile of DTaP-IPV-HB-PRP-T is similar when given concomitantly with a meningococcal C conjugate vaccine or alone.•These data support the concomitant use of DTa-IPV-HB-PRP-T vaccine with a meningococcal C conjugate vaccine. DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46–74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1–99.3] in the coadministration group and 96.1% [95%CI: 91.8–98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24.

•ProQuad® and hexavalent vaccine immunogenicity is similar if given together or alone.•ProQuad® and hexavalent vaccine have consistent safety when given together or alone.•These data support concomitant use of ProQuad® with a hexavalent vaccine. Concomitant administration of vaccines can facilitate vaccination uptake, provided that no clinically significant effect on either vaccine is identified. We investigated the concomitant administration, during the second year of life, of one dose of the combined measles, mumps, rubella and varicella vaccine (ProQuad®) with a booster dose of a hexavalent vaccine. In this multicentre, open-label study, participants were randomized to 3 groups: Group 1, concomitant administration of one dose of ProQuad® and a booster of hexavalent vaccine; Group 2, one dose of ProQuad® alone; Group 3, a booster dose of hexavalent vaccine alone. Two serum samples were collected, within 7 days prior to vaccination and Days 42–56 post-vaccination for antibody testing. Antibody response rates to measles, mumps, rubella, varicella, hepatitis B and Haemophilus influenzae type b following concomitant administration of ProQuad® and hexavalent vaccine were non-inferior compared with those following the individual vaccines. Antibody response rates to these antigens were all >95% in all groups. Antibody titres for the pertussis antigens following concomitant administration were also non-inferior to those following the individual vaccines. Antibody titres for the other valences were numerically comparable between groups with the exception of hepatitis B, Haemophilus influenzae type b, tetanus and poliomyelitis, which were higher in the concomitant than in the non-concomitant groups. The safety profiles of each vaccination regimen were comparable, with the exception of solicited ProQuad®-related injection-site reactions (Days 0–4), which occurred more frequently in the concomitant than in the non-concomitant groups. These immunogenicity data support the concomitant administration of ProQuad® with a hexavalent vaccine. The safety profile of concomitant ProQuad® and hexavalent vaccination was also in line with that of the individual Summaries of Product Characteristics.