Seroprotection Rates Research Articles

재조합 인플루엔자 백신과 불활성화 인플루엔자 백신의 면역원성 비교

To compare surrogate markers of immunogenicity between recombinant and inactivated influenza vaccines, this study conducted a systematic review and meta-analysis for each strain. Three databases of Medline (Pubmed), Embase and Cochrane Central were searched to identify all published literature up to July 2023. Out of a total of 1,658 initially identified articles, 14 randomized controlled trials were selected based on inclusion and exclusion criteria. The program R version 4.3.1 was used to estimate the mean difference of geometric mean titer (GMT) and the pooled risk ratio (RR) of seroconversion and seroprotection with 95% confidence intervals. The meta-analysis results found higher GMT effect sizes for recombinant influenza vaccines compared to inactivated vaccines for A/H3N2 (MD=124.87, 95% CI 52.63-197.11) and B/Yamagata (MD=19.89, 95% CI 7.61-32.17) strains. In terms of seroconversion rates, recombinant influenza vaccines exhibited higher seroconversion for A/H3N2 (RR=1.33, 95% CI 1.26-1.40) and B/Yamagata (RR=1.75, 95% CI 1.06-2.89) strains. Slightly higher seroprotection rates were observed for A/H3N2 (RR=1.04, 95% CI 1.02-1.07) and B/Yamagata (RR=1.07, 95% CI 1.01-1.13) strains with recombinant vaccines. The findings from this study contribute valuable evidence for regulatory decisions when introducing recombinant vaccines in South Korea.

Safety of the novel oral poliovirus vaccine type 2 (nOPV2) in infants and young children aged 1 to

Novel oral poliovirus vaccine type 2 (nOPV2) has been engineered to improve the genetic stability of Sabin oral poliovirus vaccine (OPV) and reduce the emergence of circulating vaccine-derived polioviruses. This trial aimed to provide key safety and immunogenicity data required for nOPV2 licensure and WHO prequalification. This phase 3 trial recruited infants aged 18 to <52 weeks and young children aged 1 to <5 years in The Gambia. Infants randomly assigned to receive one or two doses of one of three lots of nOPV2 or one lot of bivalent OPV (bOPV). Young children were randomised to receive two doses of nOPV2 lot 1 or bOPV. The primary immunogenicity objective was to assess lot-to-lot equivalence of the three nOPV2 lots based on one-dose type 2 poliovirus neutralising antibody seroconversion rates in infants. Equivalence was declared if the 95% CI for the three pairwise rate differences was within the -10% to 10% equivalence margin. Tolerability and safety were assessed based on the rates of solicited adverse events to 7 days, unsolicited adverse events to 28 days, and serious adverse events to 3 months post-dose. Stool poliovirus excretion was examined. The trial was registered as PACTR202010705577776 and is completed. Between February and October, 2021, 2345 infants and 600 young children were vaccinated. 2272 (96·9%) were eligible for inclusion in the post-dose one per-protocol population. Seroconversion rates ranged from 48·9% to 49·2% across the three lots. The minimum lower bound of the 95% CIs for the pairwise differences in seroconversion rates between lots was -5·8%. The maximum upper bound was 5·4%. Equivalence was therefore shown. Of those seronegative at baseline, 143 (85·6%) of 167 (95% CI 79·4-90·6) infants and 54 (83·1%) of 65 (71·7-91·2) young children seroconverted over the two-dose nOPV2 schedule. The post-two-dose seroprotection rates, including participants who were both seronegative and seropositive at baseline, were 604 (92·9%) of 650 (95% CI 90·7-94·8) in infants and 276 (95·5%) of 289 (92·4-97·6) in young children. No safety concerns were identified. 7 days post-dose one, 78 (41·7%) of 187 (95% CI 34·6-49·1) infants were excreting the type 2 poliovirus. nOPV2 was immunogenic and safe in infants and young children in The Gambia. The data support the licensure and WHO prequalification of nOPV2. Bill & Melinda Gates Foundation.

The Effects of Dairy Consumption on Vaccine Immune Response and Immunoglobulins: A Systematic Literature Review

Public health interest in vaccinations and immune protection has increased with the COVID-19 pandemic. Dairy products are an important source of protein and other nutrients, and there are unresolved research questions regarding the potential health impact of dairy products on the enhancement of immune response. A systematic literature review was conducted to synthesize the published literature reporting the effects of dairy interventions on: 1) the vaccine-specific immune response and 2) immunoglobulins in the absence of vaccination. To assess study validity and quality, we used the Academy of Nutrition and Dietetics Quality Criteria Checklist. Sixty-one studies (59 clinical trials, 1 cohort, 1 cross-sectional survey) were included, spanning 1983-2017. Ten trials evaluated the effect of dairy intervention on vaccine-specific IgG, IgA, IgM, vaccine-specific antibody titers, seroprotection rates, or seroconversion rates. Of these, 7 reported significant increases with dairy interventions for post-vaccine tetanus antibodies, mean change in tetanus antibody level, total antibody titers to flagellin from Salmonella Adelaide, mean antibody titers to influenza B, influenza-specific IgA and IgG levels, and seroconversion or seroprotection rates for influenza A and B. Fifty-six studies evaluated dairy’s effects on immunoglobulins without vaccinations. The results were heterogenous, with some studies reporting significant enhancement of immunoglobulins (IgA, IgE, or IgG), while others observed no differences between groups. Clinical relevance of the immunoglobulin changes was not investigated in these studies. Dairy products and their components could enhance the efficacy of vaccines. This review highlights the evidence gaps and provides a potential roadmap for additional research.

Efficacy of an inactivated influenza vaccine adjuvanted with Toll-like receptor ligands against transmission of H9N2 avian influenza virus in chickens

Avian influenza viruses (AIV), including the H9N2 subtype, pose a major threat to the poultry industry as well as to human health. Although vaccination provides a protective control measure, its effect on transmission remains uncertain in chickens. The objective of the present study was to investigate the efficacy of beta-propiolactone (BPL) whole inactivated H9N2 virus (WIV) vaccine either alone or in combination with CpG ODN 2007 (CpG), poly(I:C) or AddaVax™ (ADD) to prevent H9N2 AIV transmission in chickens. The seeder chickens (trial 1) and recipient chickens (trial 2) were vaccinated twice with different vaccine formulations. Ten days after secondary vaccination, seeder chickens were infected with H9N2 AIV (trial 1) and co-housed with healthy recipient chickens. In trial 2, the recipient chickens were vaccinated and then exposed to H9N2 AIV-infected seeder chickens. Our results demonstrated that BPL+ CpG and BPL+ poly(I:C) treated chickens exhibited reduced oral and cloacal shedding in both trials post-exposure (PE). The number of H9N2 AIV+ recipient chickens in the BPL+ CpG group (trial 1) was lower than in other vaccinated groups, and the reduction was higher in BPL+ CpG recipient chickens in trial 2. BPL+ CpG vaccinated chickens demonstrated enhanced systemic antibody responses with high IgM and IgY titers with higher rates of seroprotection by day 21 post-primary vaccination (ppv). Additionally, the induction of IFN-γ expression and production was higher in the BPL+ CpG treated chickens. Interleukin (IL)− 2 expression was upregulated in both BPL+ CpG and BPL+ poly(I:C) groups at 12 and 24 hr post-stimulation.

Seroconversion among children with HBsAg-positive mothers in Indonesia and factors affecting the anti-HBs titers

Background and aimAround 2% of newborns are at risk of hepatitis B virus (HBV) infection from their mothers. To prevent this, infants born to HBsAg-positive mothers are given hepatitis B immune globulin (HBIG) and hepatitis B (HB) vaccine as immunoprophylaxis. This study aims to investigate the efficacy of immunoprophylaxis in infants born to HBsAg-positive mothers and the contributing factors. MethodsThe study was conducted on a group of 87 children, ranging from nine months to under 36 months, born to HBsAg-positive mothers and received immunoprophylaxis within 24 h after birth followed by a national immunization schedule at the Community Health Center (CHC) in three administrative cities of DKI Jakarta. We measured the levels of HBsAg and anti-HBs, and utilized ordinal logistic regression models to identify factors that influence the anti-HBs titers after vaccination. ResultsOut of 87 children, only one child had positive HBsAg results. The data showed that 88.5% of the children had seroprotection with anti-HBs levels ≥10 mIU/mL. Additionally, 48.3% of the children had a high protective response with anti-HBs levels ≥100 mIU/mL, while 11.5% had a non-protective response. Children under one year of age, with a family history of HBV carriers, and who received five doses of the HB vaccine exhibited higher levels of anti-HBs titer category with adjusted OR 3.9 (95%CI: 1.3–11.6), 5.3 (95%CI: 1.1–27.4), and 8.3 (95%CI: 2–34.8), respectively. ConclusionThe administration of HBIG and HB vaccine successfully prevented vertical transmission, resulting in a high seroprotection rate.

Risk of vaccine preventable diseases in UK migrants: A serosurvey and concordance analysis

BackgroundVaccine preventable diseases (VPDs) such as measles and rubella cause significant morbidity and mortality globally every year. The World Health Organization (WHO), reported vaccine coverage for both measles and rubella to be 71 % in 2019, indicating an immunity gap. Migrants in the EU/EEA may be at high risk of VPDs due to under-immunisation and poor living conditions. However, there are limited data on VPD seroprotection rates amongst migrants living in the United Kingdom (UK). MethodsWe conducted an exploratory cross-sectional serosurvey amongst a sample of adult migrants living in Leicester, UK to: (a) determine seroprotection rates for measles, varicella zoster, and rubella in this group; (b) identify risk factors associated with seronegativity and, (c) understand if self-reported vaccine or diseases history is an effective measure of seroprotection. Participants gave a blood sample and completed a questionnaire asking basic demographic details and vaccine and disease history for the three VPDs. We summarised the data using median and interquartile range (IQR) for non-parametric continuous variables and count and percentage for categorical variables. We used logistic regression to establish predictors of seroprotection against these diseases. We examined the reliability of self-reported vaccination/disease history for prediction of seroprotection through a concordance analysis. Results149 migrants were included in the analysis. Seroprotection rates were: varicella zoster 98 %, rubella 92.6 % and measles 89.3 %. Increasing age was associated with seroprotection (OR 1.07 95 % CI 1.01–1.13 for each year increase in age). Migrants from Africa and the Middle East (aOR 15.16 95 % CI 1.31 - 175.06) and South/East Asia and Pacific regions (aOR 15.43 95 %CI 2.38 - 100.00) are significantly more likely to be seroprotected against measles as compared to migrants from Europe and Central Asia. The proportions of migrants unsure about their vaccination and disease history combined were 53.0 % for measles; 57.7 % for rubella; 43.0 % for varicella. There was no agreement between self-reported vaccination/disease history and serostatus. ConclusionOur findings suggest lower levels of seroprotection against measles in migrants living in Leicester, UK, with younger migrants and those from Europe and Central Asia more likely to lack seroprotection. A high proportion of surveyed migrants were unaware of their vaccination/disease history and self-reported vaccine/disease was a poor predictor of seroprotection against VPDs which is important for clinical decision-making regarding catch-up vaccination in this population. Our results, although derived from a small sample, suggest that there may be gaps in seroimmunity for certain VPDs in particular migrant populations. These findings should inform future qualitative studies investigating barriers to vaccine uptake in migrants and population-level seroprevalence studies aimed at determining individualised risk profiles based on demographic and migration factors.

Phase 1, randomized, rater and participant blinded placebo-controlled study of the safety, reactogenicity, tolerability and immunogenicity of H1N1 influenza vaccine delivered by VX-103 (a MIMIX microneedle patch [MAP] system) in healthy adults.

The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza. The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 μg or 7.5 μg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717. Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 μg group and 1 participant withdrew from the 7.5 μg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 μg and 7.5 μg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 μg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180. The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV.

Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.

Concomitant Administration of Ad26.RSV.preF/RSV preF Protein Vaccine and High-Dose Influenza Vaccine in Adults 65 Years and Older: A Noninferiority Trial.

Since influenza and respiratory syncytial virus (RSV) carry significant burden in older adults with overlapping seasonality, vaccines for both pathogens would ideally be coadministered in this population. Here we evaluate the immunogenicity and safety of concomitant administration of Ad26.RSV.preF/RSV preF protein and high-dose seasonal influenza vaccine (Fluzone-HD) in adults ≥65 years old. Participants were randomized 1:1 to the Coadministration or Control group. The Coadministration group received concomitant Ad26.RSV.preF/RSV preF protein and Fluzone-HD on day 1 and placebo on day 29, while the Control group received Fluzone-HD and placebo on day 1 and Ad26.RSV.preF/RSV preF protein on day 29. Influenza hemagglutination-inhibiting and RSV preF-binding antibody titers were measured postvaccination and tested for noninferiority between both groups. Safety data were collected throughout the study and analyzed descriptively. Coadministered Ad26.RSV.preF/RSV preF protein and Fluzone-HD vaccines induced noninferior immune responses compared to each vaccine administered alone. Seroconversion and seroprotection rates against influenza were similar between groups. Both vaccines remained well tolerated upon concomitant administration. Coadministration of Ad26.RSV.preF/RSV preF protein and Fluzone-HD showed an acceptable safety profile and did not hamper the immunogenicity of either vaccine, thus supporting that both vaccines can be concomitantly administered in adults ≥65 years old.

Evaluation of the efficacy, safety and influencing factors of concomitant and sequential administration of viral respiratory infectious disease vaccines: a systematic review and meta-analysis.

There is no clear conclusion on the immunogenicity and adverse events of concomitant administration the viral respiratory infectious disease vaccines. We aimed to evaluate the impact of concomitant administering viral respiratory infectious disease vaccines on efficiencies, safety and influencing factors. This meta-analysis included studies from PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, WHO COVID-19 Research, and ClinicalTrials.gov databases. Randomized controlled trials of the adult participants concomitant administered with viral respiratory infectious disease vaccine and other vaccines were included. The main outcomes were the seroconversion rate and seroprotection rate of each vaccine. Used the Mantel-Haenszel fixed effects method as the main analysis to estimate the pooled RRs and the corresponding 95% confidence intervals. The risk of bias for each trial was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, while evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A total of 21 studies comprising 14060 participants with two types of vaccines were retained for the meta-analysis. Concomitant immunization reduced the geometric mean titer (RR: 0.858, 95% CI: (0.785 to 0.939)) and the geometric mean fold rise (0.754 (0.629 to 0.902)) in the SARS-COV-2 vaccine group but increased the seroconversion rate (1.033 (1.0002 to 1.067)) in the seasonal influenza vaccine group. Concomitant administration were influenced by the type of vaccine, adjuvant content, booster immunization, and age and gender of the recipient. This meta-analysis suggested that the short-term protection and safety of concomitant administered were effective. Appropriate adjuvants, health promotion and counselling and booster vaccines could improve the efficiency and safety of Concomitant vaccination. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022343709.

A systematic review reveals that African children of 15–17 years demonstrate low hepatitis B vaccine seroprotection rates

Childhood HBV immunization remains globally fundamental to the elimination of hepatitis B virus (HBV). However, monitoring proportions of HBV vaccine seroprotection and their determinants among African Pediatric recipients is crucial. This study sought to verify extent of immune protection accorded by the HBV vaccine in African children of up to 17 years of age by pooling the prevalence of seroprotection reported by primary studies conducted in the Northern, Western, and Southern African regions. We included 19 eligible articles out of the 197 initially downloaded, published from 1999 to 2021 from African Journals Online (AJOL), EMBASE, Scopus, and PubMed. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO), University of York Centre for Reviews and Dissemination, under the registration number CRD42022361277. Significantly higher (p < 0.0001) proportion of HBV vaccine seroprotection (69.07%) was found among children under 15 years of age than children 15–17 years (32.368%), 95% CI [34.2454–39.0847%]. Whereas successful integration of the HBV vaccine on the extended programs on immunizations (EPI) has been a major achievement in the reduction of HBV infection in Africa, markedly reduced HBV vaccine seroprotection is persistently demonstrated among adolescent children 15–17 years of age. Future studies are required to clarify the need for booster dose vaccination in most at risk populations and age groups.

Safety and immunogenicity of influenza A(H3N2) component vaccine in juvenile systemic lupus erythematosus

IntroductionSeasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature.ObjectiveTo evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE.Methods24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated.ResultsJSLE patients and controls were comparable in current age [14.5 (10.1–18.3) vs. 14 (9–18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0–139.4) vs. 109.6 (95% CI 68.2–176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9–198.3) vs. 208.1 (150.5–287.8), p = 0.143] and factor increase in GMT [1.6 (1.2–2.1) vs. 1.9 (1.4–2.5), p = 0.574]. SLEDAI-2K scores [2 (0–17) vs. 2 (0–17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05).ConclusionThis is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. (www.clinicaltrials.gov, NCT03540823).

1147. A study of high-dose influenza vaccination responses compared to standard-dose in lupus patients: an open- labeled, randomized controlled study

Abstract Background Annual influenza vaccination at standard dosing in the general population is suggested. However, there may be more suitable for lupus patients. Objectives To assess the immune responses among lupus patients receiving high dose (HD) and standard (SD) quadrivalent inactivated influenza vaccine, evaluate the adverse events of the HD, and monitor the incidence of influenza infection. Methods A randomized parallel design, controlled trial was conducted from March 2021 to May 2022 at Ramathibodi Hospital. All lupus patients were stratified into two groups depending on the depth of immunosuppressive therapy received and randomized to receive either HD or SD in a 1:1 ratio. Patient demographics data and relevant information were retrieved. Blood samples were obtained for hemagglutination inhibition assay (HAI) before vaccination and 4-12 weeks after completion of the vaccination series to determine seroprotection and seroconversion rates. Results One hundred twenty-eight lupus patients were enrolled, and 109 individuals completed the HAI analysis. 54/109 patients were in the high- (HI) with mean age (mean ± SD) of 34.3 (25.2-43.4) years, and 55/109 were in the low-immunosuppressive (LI) groups with mean age (mean ± SD) of 38.2 (30.2-46.2) (p=0.018). The majority of patients had a SLEDAI-2K score of 4. The seroprotection rates against H1N1, H3N2/Hongkong, H3N2/Cambodia, B/Victoria, and B/Yamagata strains in HI and LI groups at baseline after the first and second injections were outlined as follows 1.) HI; 74.1%, 82.1%, 76.9%, 75.9%, 79.6%; 85.2%, 89.3%, 88.5%, 85.2%, 88.9%; 89.5%, 89.3%, 88.5%, 93.9%, 88.9%, and 2.) LI; 76.4%, 84.6%, 93.1%, 74.5%, 89.1%; 92.7%, 100%, 100%, 94.5%, 96.4%; 92.7%, 100%, 100%, 94.5%, 94.5%. There was one documented influenza infection during the 9-month follow-up period. The patient was in the LI group and received the SD vaccine. 19/109 (17.4%) patients had grade 1 adverse events with no difference between SD and HD. Conclusion Lupus patients’ immune response, especially those taking HI, may not be similar to healthy individuals. A higher dosage of influenza vaccination may provide a better seroprotection rate. However, real-world clinical effectiveness is yet to demonstrate, and further studies are required. Disclosures All Authors: No reported disclosures

1157. Immune Persistence and Booster Response of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) 5 Years After Primary Vaccination of Adults ≥59 Years of Age

Abstract Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It is approved for use in persons aged ≥2 years in the US and persons aged ≥1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. The second stage of a 2-stage study of MenACYW-TT, reported herein, evaluated immune persistence among older adults who received primary vaccination with either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT five years earlier at age ≥ 56 years. The immunogenicity and safety of a MenACYW-TT booster dose given to this population were also evaluated. Methods This was a Phase 3, 2-stage, randomized, open-label, multi-center study (NCT04142242) of adults aged ≥59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune persistence and response were assessed with a serum bactericidal assay using human complement (hSBA). Safety data were collected for up to 30 days after booster vaccination. All analyses were descriptive. Results Of the initial study population (N=471), 70 adults participated in Stage II of the study. At 5 years post-primary vaccination, seroprotection (hSBA ≥ 1:8) rates (SPRs) and hSBA geometric mean titers (GMTs) declined in both MenACYW-TT- and MPSV4-primed subjects, with SPRs and hSBA GMTs for serogroups A, C, W, and Y trending higher in MenACYW-TT- vs MPSV4-primed subjects (Table 1). Thirty days after booster vaccination, hSBA GMTs and SPRs increased from pre-booster for all serogroups and were, along with seroresponse rates, higher in MenACYW-TT-primed subjects compared to MPSV4-primed subjects (Table 2). Rates of AEs following booster vaccination were similar regardless of priming vaccine. No safety concerns were identified. Conclusion Five years after primary vaccination, immune persistence tended to be greater for MenACYW-TT vs MPSV4. A MenACYW-TT booster was well tolerated and immunogenic in adults ≥ 61 years, when administered 5 years after primary vaccination with either MPSV4 or MenACYW-TT. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi: Sanofi employee|Sanofi: Sanofi's Employee|Sanofi: Stocks/Bonds Katherine Galarza, MD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Alexandre Selmani, PhD, Sanofi: Sanofi employee|Sanofi: Stocks/Bonds Philipp Oster, MD, Sanofi: Sanofi employee

Strategies for Hepatitis B Virus Prevention in People Living with HIV.

Coinfection with HIV and hepatitis B virus (HBV) is common owing to shared routes of transmission, and persons with HIV-HBV coinfection experience an accelerated progression of liver disease. Despite the widespread availability of HBV vaccination, rates of seroprotection in people living with HIV (PLWH) have historically been low. In this article, we review strategies in HBV prevention among PLWH, focusing specifically on updates in HBV vaccination and chemoprophylaxis. Vaccination remains the hallmark of HBV prevention, and recent studies suggest that a double dose of HBV vaccine and Heplisav-B can improve rates of seroprotection among PLWH. The use of tenofovir-containing antiretroviral therapy (ART) has similarly been shown to provide some HBV protection in PLWH; however, this protection can be lost when switching to newer tenofovir-sparing regimens, including long-acting injectables. All HBV-susceptible persons with HIV should be vaccinated against HBV, regardless of ART regimen and CD4 count.

Immunogenicity and Safety of One versus Two Doses of Quadrivalent Inactivated Influenza Vaccine (IIV4) in Vaccine-Unprimed Children and One Dose of IIV4 in Vaccine-Primed Children Aged 3-8 Years.

Two doses of the inactivated influenza vaccine (IIV) are generally recommended for children under 9 years old. This study assessed the necessity for a second dose of quadrivalent IIV (IIV4) in children aged 3-8 years. In this randomized, open-label, paralleled-controlled study, 400 children aged 3-8 years who were vaccine-unprimed were randomly assigned at a 1:1 ratio to receive a two-dose (Group 1) or one-dose (Group 2) regimen of IIV4, and 200 who were vaccine-primed received one dose of IIV4 (Group 3). A serum sample was collected before and 28 days after the last dose to determine the hemagglutination inhibition (HI) antibody level. Adverse events were collected within 28 days after each dose. One-dose or two-doses of IIV4 were well tolerated and safe in children aged 3-8 years, and no serious adverse events related to the vaccine were reported. The seroconversion rates (SCRs) of HI antibody ranged from 61.86% to 95.86%, and the post-vaccination seroprotection rates (SPRs) were all >70% in three groups against the four virus strains. The two-dose regimen in vaccine-unprimed participants (Group 1) achieved similar SPRs in comparison with the one-dose in the vaccine-primed group (Group 3), and the SPRs in Group 1 and Group 3 were higher in vaccine-unprimed participants of the one-dose regimen (Group 2). The present study supports the recommendations of a two-dose regimen for IIV4 use in children aged 3-8 years.

Safety and immunogenicity of SIIPL Tdap, a new tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine, in healthy subjects 4–65 years of age: A Phase II/III randomized, observer-blinded, active controlled, multicenter clinical study in Germany

BackgroundThis study assessed the safety and immunogenicity of a new booster vaccine against tetanus, diphtheria, and pertussis manufactured by Serum Institute of India Pvt. Ltd (SIIPL Tdap). MethodsThe Phase II/III trial was randomized (2:1), observer blinded and active controlled. Healthy subjects aged 4–65 years received a single dose of either SIIPL Tdap or comparator Tdap vaccine (Boostrix®, GlaxoSmithKline, Belgium), and were followed-up for 30 days. Blood samples for safety and immunogenicity assessments were collected pre-vaccination and on day 30 post-vaccination. The study assessed safety and reactogenicity of SIIPL Tdap compared to the comparator Tdap as well as the co-primary immunogenicity outcomes: (i) seroprotection rates against diphtheria toxoid (DT) and tetanus toxoid (TT) and (ii) the booster response rates against pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) 30 days post-vaccination in all study subjects. A margin of −10 % was used for non-inferiority testing. Secondary outcomes included the booster response rates against DT and TT, seropositivity rates against pertussis antigens, and antibody geometric mean concentrations (GMCs) for all vaccine components. ResultsAt Day 30 post-vaccination, SIIPL Tdap was assessed as non-inferior to the comparator Tdap in terms of: i) seroprotection rates against DT (94.4 % vs. 94.9 %) and TT (99.9 % vs. 100 %) and ii) pertussis booster response rates (93.8 % vs. 88.4 % anti-PT, 89.7 % vs. 90.9 % anti-FHA and 86.3 % vs. 84.4 % anti-PRN), for SIIPL Tdap versus comparator Tdap, respectively. GMCs for anti-PT and anti-PRN were higher in subjects vaccinated with SIIPL Tdap compared to comparator Tdap. All other secondary outcomes were comparable. The overall frequency of local and systemic solicited AEs was comparable; no treatment related SAEs were reported. ConclusionsBooster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to the immunogenicity of the vaccine components and was equally well tolerated.EudraCT number: 2019-002706-46.

Tdap vaccine in pregnancy and immunogenicity of pertussis and pneumococcal vaccines in children: What is the impact of different immunization schedules?

BackgroundIn 2019, the 3 + 1 schedule for children’s vaccination (2–4–6–18 months old) was changed for a reduced 2 + 1 schedule (2–4–12 months old) in Quebec, Canada. We compared the post-booster anti-pertussis and anti-pneumococcus IgG antibody concentrations among children of Tdap-vaccinated and unvaccinated mothers for different vaccine schedules and vaccine formulations. MethodsWe conducted an observational cohort study. An invitation letter to potential participants was provided during a routine vaccination visit. Children’s blood samples were analyzed post-booster at 13 (2 + 1 schedule) or 19 (3 + 1 schedule) months of age for antibodies against pertussis antigens (pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)) and pneumococcal antigens (serotypes 4, 18C, 19A, and 19F). IgG concentrations among children of Tdap-vaccinated and unvaccinated mothers for each vaccination schedule were compared using geometric mean concentrations (GMCs) and GMC ratios (GMRs), adjusting for potentially immune-response-influencing factors (aGMR). Serotype-specific pneumococcal seroprotection rates were also compared. ResultsA total of 360 children were included for pertussis analysis and 248 for pneumococcal analysis. For the 2 + 1 schedule, 13-month-old children of Tdap-vaccinated mothers had lower GMCs against PT, FHA, and PRN, with aGMR (95 %CI) of 0.77 (0.65–0.90), 0.66 (0.55–0.79), 0.72 (0.52–0.99), respectively. For the 3 + 1 schedule, at 19 months old, the interference appeared to be attenuated (higher aGMR values). GMCs against PT were slightly higher in the 3 + 1 than the 2 + 1 schedule: 126.5 IU/ml vs 91.6 IU/ml; aGMR = 1.27. GMCs against PT, FHA and PRN were slightly higher among children who received Infanrix hexa® compared to those who received Pediacel® at 12 months old. For pneumococcal antibodies, at 13 months old, there was no strong evidence of immune interference in children of Tdap-vaccinated mothers. ConclusionInfant vaccination schedule may influence immune interference associated with maternal Tdap vaccination. More studies are needed to assess the clinical impact of this interference on children’s protection.

High Rates of Seroprotection and Seroconversion to Vaccine-Preventable Infections in the Early Post-Autologous Stem Cell Transplant Period.

In patients early post-autologous stem cell transplant, seroprotection rates were high for Hemophilus influenzae type B and tetanus toxoid (70%-90%) but lower for Streptococcus pneumoniae (30%-50%) including after revaccination. There were high rates of seropositivity (67%-86%) to measles, mumps, and rubella and varicella zoster virus. Durability of protection requires assessment.

Association of vaccine-specific regulatory T cells with reduced antibody response to repeated influenza vaccination.

Repeated annual influenza vaccinations have been associated with reduced vaccine-induced antibody responses. This prospective study aimed to explore the role of vaccine antigen-specific regulatory T (Treg) cells in antibody response to repeated annual influenza vaccination. We analyzed pre- and postvaccination hemagglutination inhibition (HI) titers, seroconversion rates, seroprotection rates, vaccine antigen hemagglutinin (HA)-specific Treg cells, and conventional T (Tconv) cells. We compared these parameters between vaccinees with or without vaccine-induced seroconversion. Our multivariate logistic regression revealed that prior vaccination was significantly associated with a decreased likelihood of achieving seroconversion for both H1N1(adjusted OR, 0.03; 95% CI, 0.01-0.13) and H3N2 (adjusted OR, 0.09; 95% CI, 0.03-0.30). Furthermore, individuals who received repeated vaccinations had significantly higher levels of pre-existing HA-specific Treg cells than those who did not. We also found that vaccine-induced fold-increases in HI titers and seroconversion were negatively correlated with pre-existing HA-specific Treg cells and positively correlated with the ratio of Tconv to Treg cells. Overall, our findings suggest that repeated annual influenza vaccination is associated with a lower vaccine-induced antibody response and a higher frequency of vaccine-specific Treg cells. However, a lower frequency of pre-existing Treg cells correlates with a higher postvaccination antibody response.