Immunization Series Research Articles

Immuno-persistence after the 4th and 5th dose of inactivated polio vaccines in school-aged children

ObjectiveThis study aimed to assess the long-term persistence of neutralising antibodies (nAb) titres and seroprotection proportions after the 4th and 5th doses of inactivated polio vaccine (IPV). MethodsSerum samples from 299 children in Hong Kong were collected and used to estimate the persistence of nAb titres and seroprotection proportions by neutralisation test. ResultsThe mean nAb titres against polioviruses type 1, 2 and 3 (PV1, PV2 and PV3) one month after receiving the 4th dose of IPV at 19 months of age were 2,068 (95% credible interval: 1,517 – 2,864), 4,705 (3,439 – 6,436) and 2,758 (1,894 – 4,086), but declined substantially in 4 years to 268 (222 – 325), 751 (630 – 900), and 411 (323 – 521), respectively. Administration of the 5th dose of IPV restored nAb titres among children aged 6-7 years, and the decline in nAb titres was slightly slower with the estimated mean titres of 355 (272 – 462), 538 (427 – 681), and 548 (378 – 786) against PV1, PV2, and PV3 at 4 years post the 5th dose. We estimated that the proportion of children who were seroprotected against PV1, PV2 and PV3 would drop below 90% at: (i) 8.2, 10.8, 8.7 years after the 4th dose; and (ii) 11.6, 11.2, 11.0 years after the 5th dose. ConclusionsThe results revealed the immuno-persistence after the 4th and 5th dose of IPV and highlighted the importance of completing immunization series to ensure high vaccination coverage, particularly among children in the developing countries affected by the COVID-19 pandemic.

Immunogenicity of a booster dose of a bivalent (Asp614Gly and omicron BA.4/5 variant) self-amplifying mRNA SARS-CoV-2 booster vaccine versus the BNT162b2 omicron BA.4/5 mRNA vaccine: a randomised phase 3 trial

We previously showed that ARCT-154, a self-amplifying mRNA COVID-19 vaccine, had improved immunogenicity and antibody persistence compared with conventional mRNA or adenovirus vector vaccines. In this study, we compared ARCT-2301, a bivalent self-amplifying mRNA vaccine (Asp614Gly and omicron BA.4/5 variant), with the bivalent Comirnaty omicron BA.4-5 vaccine, to determine whether this improved response persisted in bivalent formulations against different SARS-CoV-2 variants. This randomised, multicentre, phase 3, observer-masked, active-controlled comparative study was done at nine hospitals in Japan. Eligible participants were healthy Japanese adults, aged at least 18 years, who had previously received a full immunisation series of three to five doses of mRNA COVID-19 vaccines (Comirnaty or Spikevax [Moderna]), with the last dose received at least 3 months before screening for this trial. Participants were randomly assigned (1:1) to either ARCT-2301 or Comirnaty BA.4-5 mRNA vaccine using interactive computer-generated randomisation with a block size of four. Randomisation was stratified by gender (men vs women), age group (<65 years vs ≥65 years), type of vaccine used for last vaccination (bivalent omicron BA.1 vs bivalent omicron BA.4/5), and time since last COVID-19 vaccination (<5 months vs ≥5 months). ARCT-2301 was supplied in vials containing 100 μg lyophilised mRNA, 50 μg mRNA each coding for the full-length spike proteins of the ancestral Asp614Gly SARS-CoV-2 strain and omicron BA.4/5 variant. Immediately before use, each vial was reconstituted with 10 mL saline. The comparator original omicron BA.4/5 mRNA vaccine (Comirnaty BA.4-5) was supplied in ready-to-use vials containing a single dose of 30 μg mRNA in 0·3 mL volume. Both vaccines were administered by intramuscular injection in the deltoid of the non-dominant arm. The primary outcome of the study was to show non-inferiority of immunogenicity of ARCT-2301 versus Comirnaty BA.4-5 at day 29 as neutralising antibody geometric mean titres (GMT) and seroresponse rates against omicron BA.4/5. Primary analyses were done in a per-protocol manner. The trial is registered with the Japan Registry for Clinical Trials, jRCT2031230340. Between Sept 29 and Nov 18, 2023, we enrolled 930 participants (451 men and 479 women) to receive a booster dose of ARCT-2301 (n=465) or Comirnaty BA.4-5 (n=465). The primary immunogenicity outcome to show that the antibody response at day 29 against omicron BA.4/5 elicited by ARCT-2301 was non-inferior to that elicited with Comirnaty BA.4-5 was achieved, both by GMT ratio (1·49, 95% CI 1·26-1·76) and difference in seroresponse rate (7·2%, 95% CI 0·6-13·7). Furthermore, the differences in antibody response between the groups showed superiority for ARCT-2301 against Wuhan-Hu-1 using both criteria, with a GMT ratio of 1·45 (95% CI 1·28-1·63) and a difference in seroresponse rate of 12·5% (95% CI 5·9-19·0), and omicron XBB.1.5, with a GMT ratio of 1·63 (95% CI 1·36-1·94) and a seroresponse rate difference of 16·7% (95% CI 10·1-23·2). Both vaccines were well-tolerated with mainly mild, transient solicited adverse events and no causally related severe or serious adverse events. Boosting mRNA-immunised adults with ARCT-2301 induced superior immunogenicity compared with Comirnaty BA.4-5 against both Wuhan-Hu-1 and omicron BA.4/5 variant COVID-19, and elicited a higher response against omicron XBB.1.5. Both vaccines had similar tolerability profiles. Self-amplifying mRNA vaccines could provide a substantial contribution to pandemic preparedness and response, inducing robust immune responses with a lower dose of mRNA to allow wider and more equitable distribution. Japanese Ministry of Health, Labour, and Welfare and Meiji Seika Pharma.

MIP3α-Rel Mtb intranasal DNA vaccination induces reactive T-cell infiltration into the lungs in mice and macaques.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the leading cause of mortality due to a single infectious organism. While generally curable, TB requires a lengthy and complex antibiotic regimen, due in large part to bacteria that can shift to a persistent state in the presence of antibiotic pressure. Rel Mtb is the primary enzyme regulating the stringent response, which contributes to the metabolic shift of Mtb to a persistent state. Targeting Rel Mtb with a vaccine to eliminate persistent bacteria through the induction of Rel Mtb -specific T-cell immunity in combination with antibiotics to kill dividing bacteria has shown promise in model systems. In a mouse model of Mtb infection, a vaccine created by genetically fusing rel Mtb to the chemokine macrophage inflammatory protein 3α ( MIP3 α), a ligand for the CC chemokine receptor type 6 (CCR6) present on immature dendritic cells, has been shown to enhance T-cell responses and accelerate eradication of infection in mouse models compared to a vaccine lacking the chemokine component. In this study, immunogenicity studies in the mouse and rhesus macaque models provide evidence that intranasal administrations of the DNA form of the MipRel vaccine led to enhanced lung infiltration of T cells after a series of immunizations. Furthermore, despite similar T-cell immunity seen in PBMCs between MipRel and Rel vaccinations, lung and bronchoalveolar lavage cell samples are more enriched for cytokine-secreting T cells in MipRel groups compared to Rel groups. We conclude that intranasal immunization with a MIP-3α fusion vaccine represents a novel strategy for use of a simple DNA vaccine formulation to elicit T-cell immune responses within the respiratory tract. That this formulation is immunogenic in a non-human primate model historically viewed as poorly responsive to DNA vaccines indicates the potential for clinical application in the treatment of Mtb infection, with possible application to other respiratory pathogens. Future studies will further characterize the protective effect of this vaccination platform.

COVID-19 immunization status in children compared to their parents: a retrospective review at an upstate NY medicine/pediatrics practice

BackgroundThis study aimed to investigate the relationship between parent and child COVID-19 immunization series completion using vaccine records.MethodsA cross-sectional chart review was performed on parent and child patients at the Albany Medical Center Internal Medicine and Pediatrics practice. Patient and parent demographic data, COVID-19 immunization status, and health care worker status was collected. Patient data was further separated into 2 cohorts to account for vaccine eligibility among child age groups, with 5–11 years and 6 months-4 years cohorts. Chi square or Fisher’s exact test was used where appropriate.ResultsAcross both cohorts, 371 child patients were identified and cross-matched with corresponding parents. Neither cohort offered evidence linking child immunization series completion with the child’s race, ethnicity, or county of residence. However, rates of series completion were higher for children with private insurance versus public options in both the 5–11 years and 6 months-4 years cohorts (both p < 0.001). Children were more likely to be immunized against COVID-19 if their parents were fully immunized against COVID-19 (both p < 0.05). Children aged 6 months-4 years were more likely to be immunized against COVID-19 if their parent was a health care worker (p = 0.038).ConclusionsThis study demonstrates a significance between child insurance status, as well as between parental vaccination status and child vaccination status. Only children under 5 years were more likely to be vaccinated against COVID-19 if their parent was a health care worker.

The impact of acellular pertussis vaccination in pregnancy on the immunogenicity of acellular versus whole-cell pertussis vaccines in infancy: A protocol for a phase IV randomised, controlled mother-infant pertussis vaccine trial (The Gambian Pertussis Study, GaPs)

Background Worldwide we have yet to achieve optimal control of pertussis, an important vaccine-preventable respiratory disease that has a particularly high burden of morbidity and mortality in infants under 1 year. Pertussis immunisation in pregnancy is an effective tool to protect infants in early life. However, there are concerns regarding the impact of maternal antibodies on the infant’s subsequent vaccine responses. The exact nature, duration, and clinical significance of this interaction is poorly understood. Methods We will conduct a phase IV randomised-controlled double-blinded (pregnant women) open-label (infants) trial, GaPs, in a cohort of 600 mother-infant pairs in The Gambia. Healthy pregnant women aged between 18 and 40 years will be recruited from two government antenatal healthcare centres in the Gambian peri-urban western region. They will be randomised to receive either a pertussis booster (TdaP-IPV) or Tetanus-Toxoid (TT, control) at 28-34 weeks’ gestation. Their infants will be further randomised to receive either acellular (aP) or whole-cell pertussis (wP) vaccines as part of the primary immunisation series at 8, 12 and 16 weeks of age and then followed up for 9-months postnatally. Clinical and safety data will be collected from each maternal-infant pair alongside blood samples and mucosal lining fluid, at baseline and multiple time points post-vaccination. Outcomes The trial aims to evaluate the quantity, quality, and persistence of immune responses, at both systemic and mucosal levels, to aP versus wP-containing priming schedules in Gambian infants up to 9-months of age, as well as the impact of pertussis immunisation in pregnancy on these responses. The primary endpoint measured will be the difference in the geometric mean concentration of anti-pertussis-toxin (PT) antibody in aP compared to wP-vaccinated infants at 16-weeks and 9-months postnatally. A further in-depth systems vaccinology approach will be embedded within the trial’s secondary and exploratory endpoints.

The prevalence of post-COVID-19 vaccination syndrome and quality of life among COVID-19-vaccinated individuals

BackgroundThere were many studies conducted to determine how immunization affects people with long-term COVID. The results of those studies have caused debate as they gave rise to varying outcomes. Some evidence indicates a change in, an improvement in, a continuation of, or even a worsening of long-term COVID symptoms following vaccination. The ratio of change in antibody titers was noticeably larger in the group of people whose illnesses became worse. Hence, this study aimed to explore potential post-COVID-19 vaccination syndrome (PCVS) in vaccinated individuals and also to assess their quality of life (QoL). MethodologyBetween September 2021 and May 2023, an ambidirectional, descriptive, follow-up cohort study was conducted, enrolling participants who were 18 years of age or older, met the vaccination requirements established by the Ministry of Health and Family Welfare, Government of India, and had completed the primary immunization series with the AZD1222® or BBV152® vaccine. The prevalence of PCVS and the QoL measured using EQ-5D-5L were assessed at 1 month, 6 months, and 12 months post-COVID-19 vaccination. ResultsAZD1222® vaccine was received by 84.28% (343) of the participants, and BBV152® vaccine was received by 15.72% (64) of the study participants. A month after the primary vaccination series, 52.8% (215) of the total participants had at least 1 PCVS, 39.8% (162) at 6 months, and 64.6% (263) at 12 months. Among those who had received vaccinations, the QoL increased at 6 months to 0.975±0.08 and declined at 12 months to 0.94±0.13 from 0.949±0.13 at 1 month after receiving a primary immunization. The overall prevalence of PCVS between AZD1222®-vaccinated individuals and BBV152®-vaccinated individuals at a month post-vaccination was 54.5% vs. 43.8%, at 6 months it was 41.1% vs. 32.8%, and at 12 months it was 65.59% vs. 59.4%. The QoL between AZD1222®-vaccinated individuals and BBV152®-vaccinated individuals at a month post-vaccination was 0.95±0.13 vs. 0.95±0.126, at 6 months it was 0.98±0.08 vs. 0.97±0.07, and at 12 months it was 0.94±0.12 vs. 0.92±0.20. However, there was no statistically significant difference in the prevalence of PCVS and QoL between AZD1222® and BBV152®-vaccinated individuals.The percentage of participants who had at least one PCVS was 83.9% (146) in the group that got booster doses and 50.2% (117) in the group that did not. The QoL was 0.9±0.15 in the group receiving booster dosages and 0.96±0.11 in the group not receiving them. There was a statistically significant difference in the prevalence of PCVS and QoL between booster dose recipients and no booster dose recipients. ConclusionIn the study, we observed the prevalence of PCVS and was similar to long-term COVID; it declined over time and increased following booster immunization. Contrary to PCVS prevalence, QoL rises with time and falls after booster doses. There is no difference in the prevalence of PCVS and the quality of life among AZD1222® and BBV152®.

Childhood immunization uptake determinants in Kinshasa, Democratic Republic of the Congo: ordered regressions to assess timely infant vaccines administered at birth and 6-weeks

BackgroundDespite global efforts to reduce preventable childhood illness by distributing infant vaccines, immunization coverage in sub-Saharan African settings remains low. Further, timely administration of vaccines at birth—tuberculosis (Bacille Calmette–Guérin [BCG]) and polio (OPV0)—remains inconsistent. As countries such as Democratic Republic of the Congo (DRC) prepare to add yet another birth-dose vaccine to their immunization schedule, this study aims to improve current and future birth-dose immunization coverage by understanding the determinants of infants receiving vaccinations within the national timeframe.MethodsThe study used two ordered regression models to assess barriers to timely BCG and first round of the hepatitis B (HepB3) immunization series across multiple time points using the Andersen Behavioral Model to conceptualize determinants at various levels. The assessment leveraged survey data collected during a continuous quality improvement study (NCT03048669) conducted in 105 maternity centers throughout Kinshasa Province, DRC. The final sample included 2398 (BCG analysis) and 2268 (HepB3 analysis) women-infant dyads living with HIV.ResultsBetween 2016 and 2020, 1981 infants (82.6%) received the BCG vaccine, and 1551 (68.4%) received the first dose of HepB3 vaccine. Of those who received the BCG vaccine, 26.3%, 43.5%, and 12.8% received BCG within 24 h, between one and seven days, and between one and 14 weeks, respectively. Of infants who received the HepB3 vaccine, 22.4% received it within six weeks, and 46% between six and 14 weeks of life. Many factors were positively associated with BCG uptake, including higher maternal education, household wealth, higher facility general readiness score, and religious-affiliated facility ownership. The factors influencing HepB3 uptake included older maternal age, higher education level, household wealth, transport by taxi to a facility, higher facility general and immunization readiness scores, and religious-affiliated facility ownership.ConclusionsThis study demonstrated that the study participants’ uptake of vaccines was consistent with the country average, but not in a timely manner. Various factors were associated with timely uptake of BCG and HepB3 vaccines. These findings suggest that investment to strengthen the vaccine delivery system might improve timely vaccine uptake and equity in vaccine coverage.

1150. Invasive meningococcal disease vaccination – a targeted literature review of adolescents and parents/caregivers’ preferences

Abstract Background Invasive meningococcal disease (IMD) serogroups A, B, C, W, Y are commonly prevented by MenACWY and MenB vaccines. MenABCWY candidate vaccines could potentially provide benefits as less injections, simplified schedules, and increased uptake. However, there is limited insight on factors influencing preferences for IMD vaccines/vaccination (Vax). This targeted literature review synthesized evidence of factors influencing IMD Vax preferences in 16–23-year-old adolescents/young adults (Ado/YA) and parents/caregivers (P/CG) of 16-18 year-old adolescents. Methods PubMed and Google Scholar were searched globally to identify publications on IMD Vax attitudes and preferences (Table 1). Studies were restricted to English and published between 2005-2022. Data were extracted and synthesized from full text reviews to list IMD Vax preference attributes. Results From the 77 abstracts screened, 19 publications were extracted (Table 2) and 17 relevant for Ado/YA and P/CG. Knowledge of disease severity (20% of Ado/YA articles) and vaccine (29% of P/CG articles) were the most reported factors influencing Vax preference. Severity of disease increased Vax preference for both groups (14%), while low disease awareness limited P/CGs’ willingness to vaccinate children (14% of P/CG articles). Some Ado/YA preferred fewer injections in the immunization series due to reduced injection site discomforts (13%). P/CG preferred less injections due to less time and less physician visits, as it may reduce vaccine preparation/injection/administration and indirect costs associated with parental work loss (7%). However, their concerns over injection-related pain were a Vax barrier (14%). IMD vaccine effectiveness was recognized by Ado/YA (13%). Longer duration of protection was important for P/CG (14%), whilst herd immunity and direct protection was preferred in Ado/YA (13%). Conclusion Findings highlight IMD Vax characteristics as key considerations among Ado/YA and P/CG when making Vax decisions. To improve vaccination coverage and protection, the evidence supports preferences for vaccinations offering benefits such as fewer injections. Trade-offs between factors relevant for a IMD combination vaccine need further research. Disclosures Shahina Begum, GSK: Employee Eliazar Sabater Cabrera, PhD, GSK: Employee|GSK: Stocks/Bonds Oscar Herrera-Restrepo, PhD, GSK: Stocks/Bonds Twinkle Khera, Mtech, IQVIA: Advisor/Consultant Willings Botha, PhD, IQVIA: Advisor/Consultant Laurie Batchelder, PhD, IQVIA: Advisor/Consultant Zeki Kocaata, PhD, GSK: Stocks/Bonds

Approach to vaccinating the pediatric solid organ transplant candidate and recipient.

Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is to provide readers with a concise, practical, expert-opinion on the approach to vaccinating the SOT candidate and recipient and to supplement existing guidelines. In addition, pediatric-specific knowledge gaps in the field and future research priorities will be highlighted.

Delays in Hepatitis B Immunization Series Completion in People With Human Immunodeficiency Virus.

Studies have demonstrated low hepatitis B virus (HBV) vaccine series completion among persons with human immunodeficiency virus (HIV). We conducted a retrospective record review of persons entering HIV care at 2 clinics in Houston, Texas, between 2010 and 2018. Kaplan-Meier curves summarized time to receipt of HBV vaccines for those eligible for vaccination. We estimated the proportions of patients who had received 1, 2, or 3 HBV vaccine doses at 12 and 24 months after entry to care. A Prentice Williams and Peterson total time model was used to evaluate associations between patient characteristics and time to vaccination. Of the 5357 patients who entered care, 2718 were eligible for HBV vaccination. After 2 years of follow-up, 51.2% of those eligible had received 1 HBV vaccine, 43.2% had received 2, and 28.4% received 3 vaccines. With adjustment for significant cofactors, patients whose CD4 cell count was ≥200/μL (adjusted hazard ratio [aHR], 1.43 [95% confidence interval (CI), 1.29-1.59]) and transgender patients (1.49 [1.08-2.04]) received any given vaccine dose sooner than those with CD4 cell counts <200/μL or cisgender patients, respectively. Compared with non-Hispanic whites, Hispanic patients were vaccinated sooner (aHR, 1.28 [95% CI, 1.07-1.53]). Those with an active substance use history had a significantly longer time to vaccination than those with no substance use history (aHR, 0.73 [95% CI, .62-.85]). Strategies are needed to increase HBV vaccine completion rates in our study population, particularly among those with CD4 cell counts <200/μL or with a substance use disorder.

The prevalence of post-COVID-19 vaccination syndrome and quality of life among COVID-19-vaccinated individuals

BackgroundThere were many studies conducted to determine how immunization affects people with long-term COVID. The results of those studies have caused debate as they gave rise to varying outcomes. Some evidence indicates a change in, an improvement in, a continuation of, or even a worsening of long-term COVID symptoms following vaccination. The ratio of change in antibody titers was noticeably larger in the group of people whose illnesses became worse. Hence, this study aimed to explore potential post-COVID-19 vaccination syndrome (PCVS) in vaccinated individuals and also to assess their quality of life (QoL). MethodologyBetween September 2021 and May 2023, an ambidirectional, descriptive, follow-up cohort study was conducted, enrolling participants who were 18 years of age or older, met the vaccination requirements established by the Ministry of Health and Family Welfare, Government of India, and had completed the primary immunization series with the AZD1222® or BBV152® vaccine. The prevalence of PCVS and the QoL measured using EQ-5D-5L were assessed at 1 month, 6 months, and 12 months post-COVID-19 vaccination. ResultsAZD1222® vaccine was received by 84.28% (343) of the participants, and BBV152® vaccine was received by 15.72% (64) of the study participants. A month after the primary vaccination series, 52.8% (215) of the total participants had at least 1 PCVS, 39.8% (162) at 6 months, and 64.6% (263) at 12 months. Among those who had received vaccinations, the QoL increased at 6 months to 0.975±0.08 and declined at 12 months to 0.94±0.13 from 0.949±0.13 at 1 month after receiving a primary immunization. The overall prevalence of PCVS between AZD1222®-vaccinated individuals and BBV152®-vaccinated individuals at a month post-vaccination was 54.5% vs. 43.8%, at 6 months it was 41.1% vs. 32.8%, and at 12 months it was 65.59% vs. 59.4%. The QoL between AZD1222®-vaccinated individuals and BBV152®-vaccinated individuals at a month post-vaccination was 0.95±0.13 vs. 0.95±0.126, at 6 months it was 0.98±0.08 vs. 0.97±0.07, and at 12 months it was 0.94±0.12 vs. 0.92±0.20. However, there was no statistically significant difference in the prevalence of PCVS and QoL between AZD1222® and BBV152®-vaccinated individuals.The percentage of participants who had at least one PCVS was 83.9% (146) in the group that got booster doses and 50.2% (117) in the group that did not. The QoL was 0.9±0.15 in the group receiving booster dosages and 0.96±0.11 in the group not receiving them. There was a statistically significant difference in the prevalence of PCVS and QoL between booster dose recipients and no booster dose recipients. ConclusionIn the study, we observed the prevalence of PCVS and was similar to long-term COVID; it declined over time and increased following booster immunization. Contrary to PCVS prevalence, QoL rises with time and falls after booster doses. There is no difference in the prevalence of PCVS and the quality of life among AZD1222® and BBV152®.

Vaccine value profile for Shigella

Shigella is the leading bacterial cause of diarrhoea and the second leading cause of diarrhoeal mortality among all ages. It also exhibits increasing levels of antibiotic resistance. The greatest burden is among children under five in low- and middle-income countries (LMICs). As such, a priority strategic goal of the World Health Organization (WHO) is the development of a safe, effective and affordable vaccine to reduce morbidity and mortality from Shigella-attributable dysentery and diarrhea, including long term outcomes associated with chronic inflammation and growth faltering, in children under 5 years of age in LMICs. In addition, a safe and effective Shigella vaccine is of potential interest to travellers and military both to prevent acute disease and rarer, long-term sequelae. An effective Shigella vaccine is also anticipated to reduce antibiotic use and thereby help diminish further emergence of enteric pathogens resistant to antimicrobials.The most advanced vaccine candidates are multivalent, parenteral formulations in Phase 2 and Phase 3 clinical studies. They rely on O-antigen-polysaccharide protein conjugate technologies or, alternatively, outer membrane vesicles expressing penta-acylated lipopolysaccharide that has been detoxified. Other parenteral and oral formulations, many delivering a broader array of Shigella antigens, are at earlier stages of clinical development. These formulations are being assessed in alignment with the WHO Preferred Product Characteristics, which call for a 1 to 2 dose primary immunization series given during the first 12 months of life, ideally starting at 6 months of age.This ‘Vaccine Value Profile’ (VVP) for Shigella is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the Shigella VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers

IntroductionNanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA. MethodsThis study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 µg mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1-specific IgG antibodies 14 days post-vaccination. ResultsIn April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599–1,689), 3,855 (2,800–5,306), and 3,513 (2,554–4,833) at day 1, 15 and 29, respectively). In addition, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA. ConclusionNeedle-free delivery of 20 µg mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Clinical trial registry (on ClinicalTrial.gov)NCT05315362.

Booster Immunization Improves Memory B Cell Responses in Older Adults Unresponsive to Primary SARS-CoV-2 Immunization.

The generation of a specific long-term immune response to SARS-CoV-2 is considered important for protection against COVID-19 infection and disease. Memory B cells, responsible for the generation of antibody-producing plasmablasts upon a new antigen encounter, play an important role in this process. Therefore, the induction of memory B cell responses after primary and booster SARS-CoV-2 immunizations was investigated in the general population with an emphasis on older adults. Participants, 20-99 years of age, due to receive the mRNA-1273 or BNT162b2 SARS-CoV-2 vaccine were included in the current study. Specific memory B cells were determined by ex vivo ELISpot assays. In a subset of participants, antibody levels, avidity, and virus neutralization capacity were compared to memory B cell responses. Memory B cells specific for both Spike S1 and receptor-binding domain (RBD) were detected in the majority of participants following the primary immunization series. However, a proportion of predominantly older adults showed low frequencies of specific memory B cells. Booster vaccination resulted in a large increase in the frequencies of S1- and RBD-specific memory B cells also for those in which low memory B cell frequencies were detected after the primary series. These data show that booster immunization is important for the generation of a memory B cell response, as a subset of older adults shows a suboptimal response to the primary SARS-CoV-2 immunization series. It is anticipated that these memory B cells will play a significant role in the immune response following viral re-exposure.

Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine.

Most vaccines require several immunizations to induce robust immunity, and indeed, most SARS-CoV-2 vaccines require an initial two-shot regimen followed by several boosters to maintain efficacy. Such a complex series of immunizations unfortunately increases the cost and complexity of populations-scale vaccination and reduces overall compliance and vaccination rate. In a rapidly evolving pandemic affected by the spread of immune-escaping variants, there is an urgent need to develop vaccines capable of providing robust and durable immunity. In this work, a single immunization SARS-CoV-2 subunit vaccine is developed that can rapidly generate potent, broad, and durable humoral immunity. Injectable polymer-nanoparticle (PNP) hydrogels are leveraged as a depot technology for the sustained delivery of a nanoparticle antigen (RND-NP) displaying multiple copies of the SARS-CoV-2 receptor-binding domain (RBD) and potent adjuvants including CpG and 3M-052. Compared to a clinically relevant prime-boost regimen with soluble vaccines formulated with CpG/alum or 3M-052/alum adjuvants, PNP hydrogel vaccines more rapidly generated higher, broader, and more durable antibody responses. Additionally, these single-immunization hydrogel-based vaccines elicit potent and consistent neutralizing responses. Overall, it is shown that PNP hydrogels elicit improved anti-COVID immune responses with only a single administration, demonstrating their potential as critical technologies to enhance overall pandemic readiness.

Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.

The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6-8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population. Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080.

Kinetics of the Antibody Response to Symptomatic SARS-CoV-2 Infection in Vaccinated and Unvaccinated Individuals in the Blinded Phase of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.

Hybrid immunity is associated with more durable protection against coronavirus disease 2019 (COVID-19). We describe the antibody responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vaccinated and unvaccinated individuals. The 55 vaccine arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens (ancestral and variants of concern [VOCs]) were assessed on disease day 1 (DD1) and 28 days later (DD29). The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post-first dose. For vaccine group cases, there was a 1.88-fold rise in ancestral antispike bAbs 1 month post-disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 antispike and antinucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group. Following COVID-19, vaccinated participants had higher levels and greater breadth of antispike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.

Effects of the COVID-19 pandemic on self-reported 12-month pneumococcal vaccination series completion rates in Canada

ABSTRACT Routine childhood vaccination improves health and prevents morbidity and mortality from vaccine-preventable diseases. There are indications that the COVID-19 pandemic has negatively impacted immunization rates globally, but systematic studies on this are still lacking in Canada. This study aims to add knowledge on the pandemic’s effect on children’s immunization rates with pneumococcal vaccine using self-reported immunization data from CANImmunize. An interrupted time series analysis was conducted on aggregated monthly enrollment of children on the platform (2016–2021) and their pneumococcal immunization series completion rates (2016–2020). Predicted trends before and after the onset of the COVID19-related restriction (March 1, 2020) were compared by means of an Autoregressive Integrated Moving Average (ARIMA). The highest monthly enrollment was 3,474 new infant records observed in January 2020, and the lowest was 100 records in December 2021. The highest Self-reported pneumococcal immunization series completion rate was 78.89%, observed in February 2017, and the lowest was 6.94% in December 2021. Enrollment decreased by 1177.52 records (95% CI: −1865.47, −489.57), with a continued decrease of 80.84 records each month. Completion rates had an immediate increase of 14.57% (95% CI 4.64, 24.51), followed by a decrease of 3.54% each month. The onset of the COVID-19 related restrictions impacted the enrollment of children in the CANImmunize digital immunization platform and an overall decrease in self-reported pneumococcal immunization series completion rates. Our findings support efforts to increase catch-up immunization campaigns so that children who could not get scheduled immunization during the pandemic are not missed.

Up-to-date Immunization Coverage among Infants Attending a Clinic at a Tertiary Hospital During the Second Wave of COVID-19 Pandemic in Kathmandu, Nepal

This study aimed to evaluate the utilization and quality of routine immunization (RI) services at a tertiary hospital during the second wave of the COVID-19 pandemic period. An observational analytical study was carried out in the Immunization Clinic of a tertiary hospital in Kathmandu, Nepal. The infant cohort was enrolled over a period of 4 months and followed up for a year (April 2021 to August 2022). Up-to-date immunization (UTD) status, overall and vaccine specific drop-out rates were quantified and reasons for missed or delayed doses were elicited from caregivers. An infant who received BCG, 3 doses of Pentavalent (DPT-HEPB-HIB) and OPV containing vaccine, one dose of fractional IPV, 2 doses of Rotavirus vaccine, 3 doses of PCV and first dose of Measles-Rubella (MR1) vaccine prior to their first birthday was categorized as UTD. Dropout rates between early and later vaccine doses were defined as the percentage of children that started their immunization series, but did not complete it for some reason. Among 227 infants (44.1% female) enrolled in the study, about three-fourths (74.5%, 95% CL 68.3% to 80.0%) were identified as UTD. Among UTD infants (n=169), two-thirds of the infants (65.1%, 95% CL 57.4% to 72.3%) had received the vaccines at the recommended age milestones. Overall dropout rate (BCG-MR1) was about 19% with highest dropout between the first and third Pentavalent dose (10%). Maximum delay was seen for MR1 vaccine. Common reasons for missed or delayed visits were that the infant received vaccine at another health facility, or the infant was ill, caregivers had travelled to village/maternal home or were busy. In conclusion, three-fourths of the infant cohort had received all of the recommended vaccines as per the National immunization schedule at our immunization clinic. However, one third had delayed their visits to the clinic. While routine immunization reporting looks at the number of vaccine doses that have been administered at an immunization clinic, this study has documented a sustained utilization of RI services during the second wave of the pandemic period. The lower dropout rate for pentavalent vaccine indicates a qualitative improvement in RI services at the tertiary hospital. However, an ongoing scrutiny of immunization data recording with a progression to digital health records and provision of timely reminders to caregivers may further help to strengthen RI services at the institutional level.

Hepatitis B immunity among undergraduate nursing students: A brief report.

Health sciences students who report low/equivocal hepatitis B titers may be required to repeat the immunization series, even though the result may not indicate non-immunity. To describe hepatitis B immunity patterns, this retrospective, descriptive study utilized de-identified vaccination records and anti-HBs titers of three cohorts of sophomore nursing students entering clinical rotations in 2018-2019. Only 33% of students had initial anti-HBs quantitative serum titer ≥10mIU/ml, demonstrating immunity. After students with low/equivocal titers (n=191, 64%) were re-immunized per institution protocol, only 2% (n=7) were identified as non-responders. Cumulative costs incurred by students for revaccination and repeat titer exceeded $20,000, with a process time of up to 8 months. While rates of exposure to hepatitis B in acute care settings have steadily declined in the United States, students who go on to practice in community and public health settings have increased risk of exposure. Following best practices in demonstrating hepatitis B immunity, which include a single challenge dose followed by titer 4 weeks later, would decrease per student costs, wait time, and administrative burden associated with documentation and student counseling.