Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine States, September-November 2022.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

In silico designing of a novel polyvalent multi-subunit peptide vaccine leveraging cross-immunity against human visceral and cutaneous leishmaniasis: an immunoinformatics-based approach.

CONTEXT: Leishmaniasis is a group of vector-borne infectious diseases caused by over 20 pathogenic Leishmania species that are endemic in many tropical and subtropical countries. The emergence of drug-resistant strains, the adverse side effects of anti-Leishmania drugs, and the absence of a preventative vaccination strategy threaten the sensitive population. Recently, many groups of researchers have exploited the field of reverse vaccinology to develop vaccines, focusing chiefly on inducing immunity against either visceral or cutaneous leishmaniasis. METHODS: This present work involves retrieving twelve experimentally validated leishmanial antigenic protein sequences from the UniProt database, followed by their antigenicity profiling employing ANTIGENpro and Vaxijen 2.0 servers. MHC-binding epitopes for the same were predicted using both NetCTL 1.2 and SYFPEITHI servers, while epitopes for B cell were computed using ABCpred and BepiPred 2.0 servers. The screened epitopes with significantly higher scores were utilized for designing the vaccine construct with appropriate linkers and natural adjuvant. The secondary and tertiary structures of the synthetic peptide were determined by conditional random fields, shallow neural networks, and profile-profile threading alignment with iterative structure assembly simulations, respectively. The 3-D vaccine model was validated through CASP10-tested refinement and the MolProbity web server. Molecular docking and multi-scale normal mode analysis simulation were performed to analyze the best vaccine-TLR complex. Finally, computational immune simulation findings revealed promising cellular and humoral immune responses, suggesting that the engineered chimeric peptide is a potential broad-spectrum vaccine against visceral and cutaneous leishmaniasis.

Factors associated with incomplete vaccination and negative antibody test results for measles, mumps, and hepatitis A among children followed in the MINA-BRAZIL cohort.

Vaccination coverage has been dropping in Brazil and other countries. In addition, immune responses after vaccination may not be homogeneous, varying according to sociodemographic and clinical factors. Understanding the determinants of incomplete vaccination and negative antibody test results may contribute to the development of strategies to improve vaccination effectiveness. In this study, we aimed to investigate the frequency of vaccine adherence, factors associated with incomplete vaccination for measles, mumps, rubella (MMR) and hepatitis A, and factors associated with the seronegative test results for measles, mumps and hepatitis A at 2 years of age. This was a population-based cohort that addressed health conditions and mother/infant nutrition in Cruzeiro do Sul city, Brazil. Vaccination data were obtained from official certificates of immunization. The children underwent blood collection at the two-year-old follow-up visit; the samples were analyzed using commercially available kits to measure seropositivity for measles, mumps, and hepatitis A. We used modified Poisson regression models adjusted for covariates to identify factors associated with incomplete vaccination and negative serology after vaccination. Out of the 825 children included in the study, adherence to the vaccine was 90.6% for MMR, 76.7% for the MMRV (MMR + varicella), and 74.9% for the hepatitis A vaccine. For MMR, after the adjustment for covariates, factors associated with incomplete vaccination included: white-skinned mother; paid maternity leave; raising more than one child; lower number of antenatal consultations; and attending childcare. For hepatitis A, the factors included: white-skinned mother and not having a cohabiting partner. The factors with statistically significant association with a negative antibody test result included: receiving Bolsa Familia allowance for measles and mumps; incomplete vaccination for measles; and vitamin A deficiency for mumps. Strategies to improve the efficiency of vaccine programs are urgently needed. These include improvements in communication about vaccine safety and efficacy, and amplification of access to primary care facilities, prioritizing children exposed to the sociodemographic factors identified in this study. Additionally, sociodemographic factors and vitamin A deficiency may impact the immune responses to vaccines, leading to an increased risk of potentially severe and preventable diseases.

Cellular T-cell immune response profiling by tetravalent dengue subunit vaccine (DSV4) candidate in mice.

While most vaccines aim to develop a solid humoral and neutralizing antibody response against the pathogen, an effective vaccine candidate should be able to stimulate both the B-cell mediated humoral immunity, and T-cell mediated cellular immunity. The focus of vaccinology is rapidly gaining to generate T cell responses, which can mediate pathogen clearance and help B cells leading to protective antibody responses. Here we evaluate the cellular immune response of the pre-clinical tetravalent dengue subunit vaccine candidate, DSV4, in mice. While we have shown previously that DSV4 induces type-specific neutralizing antibody responses in mice, in this study, we show that the vaccine candidate DSV4 well induces dengue-specific T- cell responses evaluated by their ability to produce IFN-γ. In addition to IFN-γ secretion by both CD4+ and CD8+ T-cells in immunized mice, we observed that DSV4 also induces a higher frequency and cytokine functions of follicular CD4+ helper T-cells (TFH). These cytokines lead to an efficient germinal center reaction and potent B cell antibody response. Apart from TFH response, DSV4 stimulated Type 1 T helper cells (TH1) which is characteristic of a viral infection leading to secretion of pro-inflammatory cytokines and phagocyte-dependent protective immune responses. Our study highlights that DSV4 can mediate both arms of adaptive immunity-humoral and cell-mediated immunity in mice. By elucidating vaccine-specific T cell response, our work has implications in showing DSV4 as an effective, type-specific and safe dengue vaccine candidate.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

ADCC: An underappreciated correlate of cross-protection against influenza?

In this short review, we summarized the results obtained with an assay to detect influenza virus-specific antibodies that mediate ADCC, which was developed and evaluated within the framework of the IMI-funded project "FLUCOP". HA-specific ADCC mediating antibodies were detected in serum samples from children and adults pre- and post-vaccination with monovalent, trivalent, or quadrivalent seasonal influenza vaccines, or following infection with H1N1pdm09 virus. Additionally, using chimeric influenza HA proteins, the presence of HA-stalk-specific ADCC mediating antibodies after vaccination and natural infection with H1N1pdm09 virus was demonstrated. With serum samples obtained from children that experienced a primary infection with an influenza B virus, we showed that primary infection induces HA-specific ADCC-mediating antibodies that cross-reacted with HA from influenza B viruses from the heterologous lineage. These cross-reactive antibodies were found to be directed to the HA stalk region. Antibodies directed to the influenza B virus HA head mediated low levels of ADCC. Finally, vaccination with a recombinant modified vaccinia virus Ankara expressing the HA gene of a clade 1 A(H5N1) highly pathogenic avian influenza virus led to the induction of ADCC-mediating antibodies, which cross-reacted with H5 viruses of antigenically distinct clades. Taken together, it is clear that virus-specific antibodies induced by infection or vaccination have immunological functionalities in addition to neutralization. These functionalities could contribute to protective immunity. The functional profiling of vaccine-induced antibodies may provide further insight into the effector functions of virus-specific antibodies and their contribution to virus-specific immunity.

Immunogenicity and safety of concomitant and sequential administration of yellow fever YF-17D vaccine and tetravalent dengue vaccine candidate TAK-003: A phase 3 randomized, controlled study.

BACKGROUND: Yellow fever (YF) vaccination is often mandatory for travelers to YF-endemic areas. The areas with risk of YF partially overlap with those of dengue, for which there is currently no recommended vaccine available for dengue-naïve individuals. This phase 3 study assessed the immunogenicity and safety of concomitant and sequential administration of YF (YF-17D) and tetravalent dengue (TAK-003) vaccines in healthy adults aged 18-60 years living in areas of the US non-endemic for either virus. METHODS: Participants were randomized 1:1:1 to receive the following vaccinations at Months 0, 3, and 6, respectively: YF-17D+placebo, TAK-003, and TAK-003 (Group 1); TAK-003+placebo, TAK-003, and YF-17D (Group 2); or YF-17D+TAK-003, TAK-003, and placebo (Group 3). The primary objective was to demonstrate non-inferiority (upper bound of 95% confidence interval [UB95%CI] of difference <5%) of YF seroprotection rate one month following concomitant administration of YF-17D and TAK-003 (Group 3) compared with YF-17D plus placebo (Group 1). The secondary objectives included demonstration of non-inferiority of YF and dengue geometric mean titers (GMTs) (UB95%CI for GMT ratio <2.0), and safety. RESULTS: 900 adults were randomized. YF seroprotection rates one month post-YF-17D (Month 1) were 99.5% and 99.1% in Group 1 and 3, respectively, and non-inferiority was demonstrated (UB95%CI = 2.69% i.e. <5%). Non-inferiority was also demonstrated for GMTs against YF one month post-YF-17D, and against DENV-2, -3, and -4 (UB95%CI <2), but not DENV-1 (UB95%CI: 2.22), one month post-second TAK-003 vaccination. Adverse event rates following TAK-003 were consistent with previous results, and no important safety risks were identified. CONCLUSIONS: In this study, YF-17D vaccine and TAK-003 were immunogenic and well tolerated when sequentially or concomitantly administered. The non-inferiority of immune responses to YF-17D and TAK-003 was demonstrated for concomitant administration of the 2 vaccines compared to separate vaccination, except against DENV-1 but with GMTs similar to those observed in other TAK-003 trials. TRIAL REGISTRATION: ClinicalTrials.gov identified: NCT03342898.

Early Estimates of Bivalent mRNA Booster Dose Vaccine Effectiveness in Preventing Symptomatic SARS-CoV-2 Infection Attributable to Omicron BA.5- and XBB/XBB.1.5-Related Sublineages Among Immunocompetent Adults - Increasing Community Access to Testing Program, United States, December 2022-January 2023.

The SARS-CoV-2 Omicron sublineage XBB was first detected in the United States in August 2022.* XBB together with a sublineage, XBB.1.5, accounted for >50% of sequenced lineages in the Northeast by December 31, 2022, and 52% of sequenced lineages nationwide as of January 21, 2023. COVID-19 vaccine effectiveness (VE) can vary by SARS-CoV-2 variant; reduced VE has been observed against some variants, although this is dependent on the health outcome of interest. The goal of the U.S. COVID-19 vaccination program is to prevent severe disease, including hospitalization and death (1); however, VE against symptomatic infection can provide useful insight into vaccine protection against emerging variants in advance of VE estimates against more severe disease. Data from the Increasing Community Access to Testing (ICATT) national pharmacy program for SARS-CoV-2 testing were analyzed to estimate VE of updated (bivalent) mRNA COVID-19 vaccines against symptomatic infection caused by BA.5-related and XBB/XBB.1.5-related sublineages among immunocompetent adults during December 1, 2022­January 13, 2023. Reduction or failure of spike gene (S-gene) amplification (SGTF) in real-time reverse transcription­polymerase chain reaction (RT-PCR) was used as a proxy indicator of infection with likely BA.5-related sublineages and S-gene target presence (SGTP) of infection with likely XBB/XBB.1.5-related sublineages (2). Among 29,175 nucleic acid amplification tests (NAATs) with SGTF or SGTP results available from adults who had previously received 2­4 monovalent COVID-19 vaccine doses, the relative VE of a bivalent booster dose given 2­3 months earlier compared with no bivalent booster in persons aged 18­49 years was 52% against symptomatic BA.5 infection and 48% against symptomatic XBB/XBB.1.5 infection. As new SARS-CoV-2 variants emerge, continued vaccine effectiveness monitoring is important. Bivalent vaccines appear to provide additional protection against symptomatic BA.5-related sublineage and XBB/XBB.1.5-related sublineage infections in persons who had previously received 2, 3, or 4 monovalent vaccine doses. All persons should stay up to date with recommended COVID-19 vaccines, including receiving a bivalent booster dose when they are eligible.

Optimizing timing of adolescent vaccines: Impact of initiating HPV vaccination before Tdap or meningococcal vaccination on timely completion of the HPV vaccine series.

To explore the impact on timely series completion of initiating the HPV vaccine series prior to other vaccines in the adolescent platform (Tdap or meningococcal vacccines), we created a cohort of children aged 9 in 2015 who were continuously enrolled through the age of 13 (2019) from a national administrative database of employee-sponsored insurance in the United States (MarketScan). Logistic regressions were used to predict the odds of HPV vaccine series completion among those who started the series prior to, concurrent with, or after receiving Tdap or meningococcal vaccination. The cohort included 100,857 eligible children. Compared with adolescents who received their HPV and Tdap or HPV and meningococcal vaccinations concurrently, those who received HPV prior to other vaccines had higher completion (aOR = 1.38 for Tdap, aOR 1.62 for meningococcal), while those who received their HPV vaccination after other vaccines had lower odds of HPV vaccine series completion (aOR = 0.68 for Tdap, aOR = 0.62 for meningococcal). Other factors associated with series completion included female sex, residing in an urban (vs. rural) area, residing in the Northeast, and receiving primary care from a pediatrician (vs. family medicine physician). These data indicate that beginning the HPV vaccine series prior to the adolescent platform may improve on-time series completion.

Immunogenicity and safety of seasonal influenza vaccines in children under 3 years of age.

INTRODUCTION: Despite children aged 6-35 months developing more severe influenza infections, not all countries include influenza vaccines in their national immunization programs. AREAS COVERED: This literature review examines the efficacy, immunogenicity, and safety of seasonal trivalent influenza vaccines (TIVs) and quadrivalent influenzae vaccines (QIVs) in children 6-35 months old to determine if greater valency promotes greater protection while maintaining a similar safety profile. EXPERT OPINION: TIVs and QIVs are safe for children under 3 years old. TIVs and QIVs provided good seroprotection, and immunogenicity (GMT, SCR, and SPR) meeting recommended levels set by CHMP (European) and CBER (USA). However, as QIVs carry two influenza B strains and TIVs only one, QIVs has an overall higher seroprotection against particularly influenza B. Vaccines containing adjuncts had better immunogenicity, particularly after the first dose. Seroprotection of all vaccines lasted 12 months. Increasing the dosage from 0.25 mL to 0.5 mL did not cause more systemic or local side-effects. Further comparisons of efficacy, and wider promotion of influenza vaccines in general are required in preschool children.

Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing Symptomatic SARS-CoV-2 Infection Among Children Aged 3-5 Years - Increasing Community Access to Testing Program, United States, July 2022-February 2023.

On June 18, 2022, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for use of the 2-dose monovalent Moderna COVID-19 vaccine as a primary series for children aged 6 months-5 years* and the 3-dose monovalent Pfizer-BioNTech COVID-19 vaccine as a primary series for children aged 6 months-4 years,† based on safety, immunobridging, and limited efficacy data from clinical trials (1-3). Monovalent mRNA vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection was evaluated using the Increasing Community Access to Testing (ICATT) program, which provides SARS-CoV-2 testing to persons aged ≥3 years at pharmacy and community-based testing sites nationwide§ (4,5). Among children aged 3-5 years with one or more COVID-19-like illness symptoms¶ for whom a nucleic acid amplification test (NAAT) was performed during August 1, 2022-February 5, 2023, VE of 2 monovalent Moderna doses (complete primary series) against symptomatic infection was 60% (95% CI = 49% to 68%) 2 weeks-2 months after receipt of the second dose and 36% (95% CI = 15% to 52%) 3-4 months after receipt of the second dose. Among symptomatic children aged 3-4 years with NAATs performed during September 19, 2022-February 5, 2023, VE of 3 monovalent Pfizer-BioNTech doses (complete primary series) against symptomatic infection was 31% (95% CI = 7% to 49%) 2 weeks-4 months after receipt of the third dose; statistical power was not sufficient to estimate VE stratified by time since receipt of the third dose. Complete monovalent Moderna and Pfizer-BioNTech primary series vaccination provides protection for children aged 3-5 and 3-4 years, respectively, against symptomatic infection for at least the first 4 months after vaccination. CDC expanded recommendations for use of updated bivalent vaccines to children aged ≥6 months on December 9, 2022 (6), which might provide increased protection against currently circulating SARS-CoV-2 variants (7,8). Children should stay up to date with recommended COVID-19 vaccines, including completing the primary series; those who are eligible should receive a bivalent vaccine dose.

Outcomes of meningococcal serogroup B disease in children after implementation of routine infant 4CMenB vaccination in England: an active, prospective, national surveillance study.

BACKGROUND: In 2015, the UK included 4CMenB, a multi-component, recombinant protein-based vaccine against meningococcal serogroup B (MenB) disease, in the national infant immunisation programme. We aimed to assess the effect of 4CMenB vaccination on the severity of MenB disease presentation and outcomes. METHODS: In this active, prospective, national surveillance study, we used data from the UK Health Security Agency national surveillance of meningococcal disease. We included data from follow-up of children younger than 5 years with laboratory-confirmed MenB disease who were eligible for 4CMenB vaccination with general practice 3-6 months after disease onset. All invasive MenB isolates were tested using the Meningococcal Antigen Typing System to determine whether the isolate was potentially preventable by 4CMenB. Admission to intensive care, death, and, when possible, reported sequelae in survivors were reviewed alongside vaccine status. For the epidemiological analysis, we compared laboratory-confirmed MenB disease cases before 4CMenB implementation (Sept 1, 2010, to March 31, 2015) with those after implementation (Sept 1, 2015, to March 31, 2020). For clinical follow-up and outcomes, we included all children younger than 5 years with laboratory-confirmed MenB disease between Sept 1, 2015, and March 31, 2021. FINDINGS: Between Sept 1, 2015, and March 31, 2021, there were 371 cases of MenB disease in children younger than 5 years, including 256 (69%) in those younger than 1 year and 128 (35%) in those younger than 3 months. After the introduction of 4CMenB, the peak age of patients with MenB disease shifted from 5-6 months to 1-3 months. Overall, 108 (29%) of 371 children were too young for vaccination, unvaccinated, or developed MenB disease within 14 days of the first dose. Of 110 meningococcal strains characterised, 11 (92%) of 12 were potentially preventable by 4CMenB in unvaccinated children compared with 53 (66%) of 80 in partly vaccinated and 11 (69%) of 16 in fully vaccinated children. 78 (21%) of 371 children required intensive care, and the case fatality ratio was 5% (17 of 371), with 11 of 17 deaths occurring before 1 year of age, including seven in infants who were too young (<8 weeks) for vaccination. Of 354 survivors, 57 (16%) had 74 sequelae reported; 45 (61%) of 74 were neurological, 17 (23%) were physical, two (3%) were behavioural or psychological, and ten (14%) were other complications. Prevalence of sequelae was similar in unvaccinated (15 [15%] of 98) and vaccinated (42 [16%] 256) children, as were composite outcomes of death or sequelae, and intensive care or death or sequelae. INTERPRETATION: Cases of MenB disease in vaccine-eligible children declined after 4CMenB implementation, but morbidity in vaccinated and unvaccinated children remained unchanged, highlighting the importance of vaccination to prevent MenB disease. The lower peak age of infants with MenB disease after 4CMenB implementation, with a higher case fatality ratio in young infants, highlights the importance of timely vaccination. FUNDING: UK Health Security Agency.

Parental acceptance of and preferences for administration of routine varicella vaccination in the UK: A study to inform policy.

OBJECTIVES: To explore acceptability of and preferences for the introduction of varicella vaccination to the UK childhood immunisation schedule. DESIGN: We conducted an online cross-sectional survey exploring parental attitudes towards vaccines in general, and varicella vaccine specifically, and their preferences for how the vaccine should be administered. PARTICIPANTS: 596 parents (76.3% female, 23.3% male, 0.4% other; mean age 33.4 years) whose youngest child was aged 0-5 years. MAIN OUTCOME MEASURES: Willingness to accept the vaccine for their child and preferences for how the vaccine should be administered (in combination with the MMR vaccine [MMRV], on the same day as the MMR vaccine but as a separate injection [MMR + V], on a separate additional visit). RESULTS: 74.0% of parents (95% CI 70.2% to 77.5%) were extremely/somewhat likely to accept a varicella vaccine for their child if one became available, 18.3% (95% CI 15.3% to 21.8%) were extremely/somewhat unlikely to accept it and 7.7% (95% CI 5.7% to 10.2%) were neither likely nor unlikely. Reasons provided by parents likely to accept the vaccine included protection from complications of chickenpox, trust in the vaccine/healthcare professionals, and wanting their child to avoid their personal experience of chickenpox. Reasons provided by parents who were unlikely included chickenpox not being a serious illness, concern about side effects, and believing it is preferable to catch chickenpox as a child rather than as an adult. A combined MMRV vaccination or additional visit to the surgery were preferred over an additional injection at the same visit. CONCLUSIONS: Most parents would accept a varicella vaccination. These findings highlight parents' preferences for varicella vaccine administration, information needed to inform vaccine policy and practice and development of a communication strategy.

Recombinant Pseudorabies Virus Usage in Vaccine Development against Swine Infectious Disease.

Pseudorabies virus (PRV) is the pathogen of pseudorabies (PR), which belongs to the alpha herpesvirus subfamily with a double stranded DNA genome encoding approximately 70 proteins. PRV has many non-essential regions for replication, has a strong capacity to accommodate foreign genes, and more areas for genetic modification. PRV is an ideal vaccine vector, and multivalent live virus-vectored vaccines can be developed using the gene-deleted PRV. The immune system continues to be stimulated by the gene-deleted PRVs and maintain a long immunity lasting more than 4 months. Here, we provide a brief overview of the biology of PRV, recombinant PRV construction methodology, the technology platform for efficiently constructing recombinant PRV, and the applications of recombinant PRV in vaccine development. This review summarizes the latest information on PRV usage in vaccine development against swine infectious diseases, and it offers novel perspectives for advancing preventive medicine through vaccinology.

Immunoinformatics design of multivalent epitope vaccine against monkeypox virus and its variants using membrane-bound, enveloped, and extracellular proteins as targets.

Introduction: The current monkeypox (MPX) outbreak, caused by the monkeypox virus (MPXV), has turned into a global concern, with over 59,000 infection cases and 23 deaths worldwide. Objectives: Herein, we aimed to exploit robust immunoinformatics approach, targeting membrane-bound, enveloped, and extracellular proteins of MPXV to formulate a chimeric antigen. Such a strategy could similarly be applied for identifying immunodominant epitopes and designing multi-epitope vaccine ensembles in other pathogens responsible for chronic pathologies that are difficult to intervene against. Methods: A reverse vaccinology pipeline was used to select 11 potential vaccine candidates, which were screened and mapped to predict immunodominant B-cell and T-cell epitopes. The finalized epitopes were merged with the aid of suitable linkers, an adjuvant (Resuscitation-promoting factor), a PADRE sequence (13 aa), and an HIV TAT sequence (11 aa) to formulate a multivalent epitope vaccine. Bioinformatics tools were employed to carry out codon adaptation and computational cloning. The tertiary structure of the chimeric vaccine construct was modeled via I-TASSER, and its interaction with Toll-like receptor 4 (TLR4) was evaluated using molecular docking and molecular dynamics simulation. C-ImmSim server was implemented to examine the immune response against the designed multi-epitope antigen. Results and discussion: The designed chimeric vaccine construct included 21 immunodominant epitopes (six B-cell, eight cytotoxic T lymphocyte, and seven helper T-lymphocyte) and is predicted non-allergen, antigenic, soluble, with suitable physicochemical features, that can promote cross-protection among the MPXV strains. The selected epitopes indicated a wide global population coverage (93.62%). Most finalized epitopes have 70%-100% sequence similarity with the experimentally validated immune epitopes of the vaccinia virus, which can be helpful in the speedy progression of vaccine design. Lastly, molecular docking and molecular dynamics simulation computed stable and energetically favourable interaction between the putative antigen and TLR4. Conclusion: Our results show that the multi-epitope vaccine might elicit cellular and humoral immune responses and could be a potential vaccine candidate against the MPXV infection. Further experimental testing of the proposed vaccine is warranted to validate its safety and efficacy profile.

A novel high throughput plate-based method for 2-PE quantification in novel multidose vaccines (R21 malaria, Covishield and Covovax) and combination vaccines (Hexavalent).

Multidose presentation of vaccines is the most preferred choice, for mass immunization particularly during pandemics. WHO also recommends multidose containers of fill finished vaccines for programmatic suitability and global immunizations programmes. However, multidose vaccine presentations requires inclusion of preservatives to prevent contaminations. 2-Phenoxy ethanol (2-PE) is one such preservative which is being used in numerous cosmetics and many vaccines recently. Estimation of 2-PE content in multidose vials is a crucial quality control parameter to ensure in use stability of the vaccines. Presently available conventional methods, have their own limitation in terms of being time consuming, requiring sample extraction, large sample volume requirement etc. Therefore, a robust, simple, high-throughput method with a low turnaround time was required, which can quantitate 2-PE content in the conventional combination vaccines as well as new generation complex VLP based vaccines. In order to address this issue, a novel absorbance-based method has been developed. This novel method specifically detects 2-PE content in Matrix M1 adjuvanted R21 malaria vaccine, nano particle and viral vector based covid vaccines and combination vaccines like Hexavalent vaccine. The method has been validated for parameters such as linearity, accuracy and precision. Importantly, this method works even in presence of high amounts of proteins and residual DNA. Considering the advantages associated with method under study, this method can be used as an important in process or release quality parameter to estimate the 2-PE content in various vaccines containing 2-PE in multidose presentations.

Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models.

Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve control of the COVID-19 pandemic. We compare monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein in a transgenic mouse and a Wistar rat model. The blended low-dose bivalent mRNA vaccine contains half the mRNA of each respective monovalent vaccine, but induces comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, antigen-specific CD4+ and CD8+ responses, and protects transgenic female mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduces viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized female Wistar rats also contain neutralizing antibodies against the B.1.1.529 (Omicron BA.1 and BA.5) variants. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins are feasible approaches for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants.