Vaccine Group Research Articles

Safety and Immunogenicity of Concomitant Administration and Combined Administration of Bivalent BNT162b2 COVID-19 Vaccine and Bivalent RSVpreF Respiratory Syncytial Virus Vaccine with or Without Quadrivalent Influenza Vaccine in Adults ≥ 65 Years of Age

Concomitant administration may improve vaccination rates. This analysis of a phase 1/2 randomized study included 1073 healthy ≥65-year-olds who previously received ≥3 mRNA COVID-19 vaccine doses. Participants received concomitantly administered RSVpreF and bivalent BA.4/BA.5-adapted BNT162b2 vaccine (concomitant administration) with or without quadrivalent influenza vaccine (QIV), admixed combined RSVpreF + BNT162b2 vaccine (combined vaccine) with or without QIV, RSVpreF, BNT162b2, or QIV. Immunogenicity objectives included demonstrating the noninferiority of neutralizing antibody titers elicited by concomitant administration and combined vaccine compared with RSVpreF or BNT162b2 administered alone, and by concomitant administration and combined vaccine given with QIV compared with RSVpreF, BNT162b2, and QIV alone. Reactogenicity (≤7 days) and safety ≤1 month (adverse events (AEs)) and ≤6 months (serious AEs (SAEs)) after vaccination were assessed. Noninferiority for all immunogenicity comparisons was demonstrated. All vaccine groups were well tolerated; no new safety concerns were identified. Reactogenicity was mostly mild/moderate with rates generally similar across groups, except injection site pain and fatigue, which were less frequent with RSVpreF + placebo vs. other groups. AEs were infrequent, mostly mild/moderate, occurring at similar frequencies across groups. No AEs leading to study withdrawal or vaccine-related SAEs were reported. Favorable safety and tolerability alongside similar immunogenicity provide support for concomitant or combined use of RSVpreF and BNT162b2, with or without QIV, to help protect older adults from these important respiratory pathogens (NCT05886777).

Immunogenicity and safety of live attenuated influenza vaccine in children aged 3-17years in China.

(1) Background: The administration of a live attenuated influenza vaccine (LAIV) has emerged as a viable option for preventing pediatric infections. The LAIV vaccine is available in China based on efficacy results. However, LAIV immunogenicity in children aged 3-17years old in China has not yet to be studied and reported broadly. (2) Methods: This is a substudy investigating the immunogenicity and safety of the LAIV under a Phase 3, multicentre, randomized, double-blind, placebo-controlled trial. A total of 3000 participants were enrolled in a randomized, double-blind, placebo-controlled trial, split in half between vaccine and placebo, was conducted to evaluate a single LAIV dose in this age group. Hemagglutination inhibition (HI) antibody titers and incidence of adverse events were used to evaluate immunogenicity and safety, respectively. (3) Results: Although there was no significant difference in frequencies of all solicited or unsolicited AEs, nasal congestion, headache, and muscle pain were statistically significantly more frequent in vaccine recipients as compared to placebo Seroconversions and geometric mean fold increases in HI antibody titers against all strains were significantly higher in the vaccine group than in the placebo group. (4) Conclusions: The LAIV is safe and immunogenic in Chinese children and adolescents.

The Relationship Between Long Covid Symptoms and Vaccination Status in COVID-19 Survivors.

The positive effects of vaccination status on the course of Long COVID symptoms have not been fully elucidated. Our aim is to determine the most common Long COVID symptoms in patients monitored in the COVID-19 follow-up clinic and to examine whether there is a difference between the recovery rates of those who are vaccinated and those who are not vaccinated. Between December 1, 2020 and April 30, 2022, prospectively collected data of 916 patients who were admitted to the COVID-19 follow-up outpatient clinic of a tertiary hospital for the first time were evaluated as a retrospective cohort in this study. The frequencies of the ten most common symptoms in the first and last examinations of 478 patients with Long COVID symptoms were determined, and their recovery was compared. Patients were divided into two groups according to their vaccination status. The values showing the recovery rates obtained for these two groups were compared between themselves again. The average age of the patients in the study group was 54.43 ± 11.71 years, and 255 (53.3%) were male. The median follow-up period was 10 months. 84.7% of patients had received at least one dose of vaccine. Statistically significant results were found for improvement in all ten symptoms in vaccinated patients compared to the never-vaccinated group. There was no statistically significant difference between the CoronaVac, BNT162b2, and heterologous (CoronaVac+ BNT162b2) vaccine groups. Factors affecting recovery for the three most common symptoms (dyspnea, fatigue, forgetfulness) were examined with univariate logistic regression analysis, and only vaccination or non-vaccination was found to be a significant risk factor. This study showed that receiving vaccination may be effective in improving Long COVID symptoms. Although there were no statistically significant differences between the inactive vaccine CoronaVac, the mRNA vaccine BNT162b2, and the heterologous (CoronaVac+ BNT162b2) vaccine in terms of reducing Long COVID symptoms, higher recovery rates were detected in those who received the mRNA vaccine BNT162b2.

Durability of immunogenicity at 5 years after a single dose of human papillomavirus vaccine compared with two doses in Tanzanian girls aged 9-14 years: results of the long-term extension of the DoRIS randomised trial.

WHO has recommended that one dose of human papillomavirus (HPV) vaccine can be given to individuals aged 9-20 years to prevent HPV infection. Estimating durability of immune responses after a single dose in the target age for vaccination is important. We report immunogenicity results in Tanzanian girls up to 5 years after receiving a dose. In this open-label, randomised controlled trial (the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls [DoRIS] trial), 930 Tanzanian schoolgirls aged 9-14 years were enrolled and randomly allocated to receive one, two, or three doses of either the two-valent vaccine (Cervarix; GSK, Wavre, Belgium) or nine-valent vaccine (Gardasil-9; Merck Sharp & Dohme, Haarlem, Netherlands). Seropositivity specific to HPV16 or HPV18, antibody geometric mean concentrations (GMCs), and antibody avidity were measured annually up to month 36. Participants in the one-dose and two-dose groups were followed annually in a long-term extension of the DoRIS trial to month 60; the primary outcome was seropositivity specific to HPV16 or HPV18 comparing one dose with two doses. Single-dose seropositivity for HPV16 IgG antibodies at month 60 with either vaccine was more than 99% and non-inferior to two doses. 98% of girls in the one-dose two-valent vaccine group and 93% in the one-dose nine-valent group were seropositive for HPV18 at month 60; however, the non-inferiority criteria for HPV18 seropositivity comparing one dose with two doses were not met. Although HPV16 and HPV18 antibody GMCs after one dose were lower than those observed after two doses, antibody GMCs in the one-dose groups remained stable from month 12 to month 60. There was no evidence of a difference between the one-dose and two-dose groups in HPV16 or HPV18 antibody avidity at month 36 for either vaccine. A single dose of HPV vaccine in girls aged 9-14 years continues to provide stable immune responses 5 years after vaccination, although ongoing surveillance for potential waning immunity after a single dose is needed. Participants are being followed up to 9 years after vaccination. UK Department of Health and Social Care, UK Foreign, Commonwealth & Development Office, Global Challenges Research Fund, UK Medical Research Council, and the Wellcome Trust through the Joint Global Health Trials Scheme; Bill & Melinda Gates Foundation.

164. Effectiveness of Adjuvanted Inactivated Influenza Vaccine versus High-Dose Inactivated Influenza Vaccine Against PCR-Confirmed Influenza among Adults ≥65 years: A Pragmatic Randomized Study

Abstract Background In the US, adults aged ≥65 years are recommended to receive an adjuvanted or higher dose influenza vaccine. Adjuvanted (aIIV) and high-dose (HD-IIV) inactivated influenza vaccines were similarly effective against influenza in several studies based on diagnostic codes. However, less is known about their relative vaccine effectiveness (rVE) against laboratory-confirmed influenza and they have never been compared in a randomized study. We assessed the rVE of adjuvanted vs. high-dose vaccines against PCR-confirmed influenza in adults aged ≥65 years at Kaiser Permanente Northern California (KPNC). Methods During the 2023-2024 influenza season, we randomized all KPNC facilities to administer aIIV vs. HD-IIV in alternating weeks to achieve balance between the two vaccine groups. Individuals received either aIIV or HD-IIV depending on which facility and week they sought vaccination. The primary outcome was PCR-confirmed influenza in any clinical setting. Secondary outcomes were hospitalizations or emergency department (ED) visits for PCR-confirmed influenza and hospitalizations for community-acquired pneumonia (CAP). Using Cox regression on a calendar timeline, we estimated the relative vaccine effectiveness (rVE) of aIIV vs. HD-IIV as 1 minus the adjusted hazard ratio, adjusted for age, sex, race/ethnicity, and other covariates. Results The study population included 429,600 individuals; 212,887 (49.6%) received aIIV and 216,723 (50.4%) received HD-IIV. Baseline characteristics were well balanced between the two groups (Table 1). There were 836 cases of PCR-confirmed influenza (3.9 per 1000 persons) after aIIV and 867 cases (4.0 per 1000 persons) after HD-IIV. Comparing aIIV with HD-IIV, the rVE against PCR-confirmed influenza was 1.5% (95% CI: -8.4%, 10.5%; Table 2). AIIV and HD-IIV also did not differ in effectiveness against PCR-confirmed influenza hospitalizations/ED visits (rVE: 9.1%; CI: -3.9%, 20.4%) and CAP hospitalizations (rVE: 1.0%; CI: -11.4%, 12.0%). Conclusion In this large, pragmatic randomized study in adults aged ≥65 years during the 2023-2024 influenza season, adjuvanted and high-dose influenza vaccines did not differ in effectiveness against laboratory-confirmed influenza. Disclosures Mendel Haag, PhD, PharmD, CSL Seqirus: Employee|CSL Seqirus: Stocks/Bonds (Public Company) Ian McGovern, MPH, CSL Seqirus: employee|CSL Seqirus: Stocks/Bonds (Public Company) Bin Zhang, ScD, MA, CSL Seqirus: Employee|CSL Seqirus: Stocks/Bonds (Public Company) Juliet Dang, PhD, MS, CSL Seqirus: Employee|CSL Seqirus: Stocks/Bonds (Public Company) Nicola P. Klein, MD, PhD, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support

P-25. Evaluating the Immunogenicity and Safety of Either Two High-Dose or Two Standard-Dose Influenza Vaccines Over Two Consecutive Seasons in Adult Hematopoietic Cell Transplant Recipients

Abstract Background Adult hematopoietic cell transplant (HCT) recipients are at high risk of influenza complications but have suboptimal immune responses to influenza vaccines. Our previous phase II trial in adult HCT recipients demonstrated that two doses of high-dose trivalent influenza vaccine (HD-TIV) were associated with higher hemagglutination inhibition (HAI) antibody responses than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV), with similar safety profiles. This sub-study aims to characterize immunogenicity and safety of this vaccination strategy in consecutive influenza seasons. Methods A subset of participants from our initial study were re-enrolled in a consecutive season using the same dosing regimen. HAI titers were measured at baseline and 4–6 weeks post-vaccination for each dose in both years. We calculated the geometric mean fold rise (GMFR) in HAI titers and used linear mixed-effects models to determine adjusted geometric mean ratios (aGMRs). Injection-site and systemic reactions were documented for 7 days post-vaccination. Results A total of 43 participants were re-enrolled (n=20 for SD-QIV and n=23 for HD-TIV). Baseline characteristics were similar between groups (Table 1). In the second year, post-dose 1 GMFRs for both SD-QIV and HD-TIV were higher compared to post-dose 1 titers in the first year across all antigens (Table 2). HAI titers were higher for all post-vaccination visits and dose groups in the second year compared to the first year (Figure 1). aGMR comparisons between HD-TIV and SD-QIV favored HD-TIV for A/H1N1, A/H3N2, and B/Victoria antigens in both years, with statistical significance for A/H1N1 after a single dose in the second year (aGMR, 3.21; 95% CI,1.06–9.70). Injection-site and systemic reactions were generally similar between groups in year 2 (Figure 2).Figure 1.Point estimates and 95% confidence intervals for geometric mean HAI titers at visits 1, 2, and 3 in year 1, as well as visits 1, 2, and 3 in the repeater year (denoted by “R”), stratified by influenza antigens (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata), and by dose group (standard-dose quadrivalent influenza vaccine [SD-QIV] and high-dose trivalent influenza vaccine [HD-TIV]). Note that B/Yamagata is not included in HD-TIV. Conclusion In the second year, a single dose of HD-TIV or SD-QIV was more immunogenic than two doses of the same formulation in the first year, with HD-TIV demonstrating superior immunogenicity against A/H1N1. The safety profile across both vaccine formulations were similar.Figure 2.Relative frequencies of any injection-site and systemic reactions within 7 days of each vaccination for both vaccine groups (standard-dose quadrivalent influenza vaccine [SD-QIV] vs high-dose trivalent influenza vaccine [HD-TIV]) following each vaccine dose. Disclosures Edgar T. Overton, MD, ViiV Healthcare: Employment Michael Ison, MD MS, GlaxoSmithKline: Grant/Research Support|UpToDate: Royalties Steven A. Pergam, MD, MPH, Cidara: Participate in company sponsored clinical trial|F2G: Participate in company sponsored clinical trial|Global Life Technologies: Grant/Research Support|Symbio: Participate in company sponsored clinical trial Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support

220. A Phase 2 Double-Blind, Placebo-Controlled Study Showing Oral Tableted Norovirus Vaccine VXA-G1.1-NN is Immunogenic, Efficacious, and Reduces Viral Shedding Following Norovirus Challenge

Abstract Background Norovirus (NV) is a leading cause of acute gastroenteritis worldwide. Currently no specific therapy exists for norovirus gastroenteritis (NVG). VXA-G1.1-NN is a nonreplicating adenovirus-vectored thermostable oral NV vaccine shown in clinical trials to be safe, well-tolerated and generates robust serum and mucosal immune responses. This study investigated safety, immunogenicity, and protective efficacy of VXA-G1.1-NN following NV GI.1 challenge.Figure 1.Clinical outcomes (norovirus infection and norovirus gastroenteritis) after norovirus challenge 28 days post vaccination with VXA-G1.1-NN or placebo Methods 165 healthy adults ages 18-49 were randomized 1:1 to a single oral vaccination of VXA-GI.1-NN or placebo. At 28 days post-vaccination, 141 eligible subjects were challenged with 1x106 genomic copies NV GI.1 inoculum. Solicited symptoms of reactogenicity were recorded for 1 week after vaccination and unsolicited adverse events (AEs) through 28 days post challenge. NVG was assessed by incidence of acute gastroenteritis (AGE) with evidence of NV+ infection. NV shedding was evaluated by qPCR in stool and emesis. VP1-specific GI.1 IgA antibody secreting cells (ASC), serum IgA and IgG, and Norovirus Blocking Antibody Assay (NBAA) were assessed. Totality of evidence analysis was used to assess overall vaccine protective effect.Figure 2.Viral shedding in stool by qPCR through 7 days post challenge with GI.1 NN virus inoculum following vaccination with VXA-G1.1-NN or placebo Results VXA-G1.1-NN was safe and well tolerated.VXA-G1.1-NN induced strong serum and cellular immunogenicity with substantial increases in VP1 GI.1- specific ASC and serum antibodies. Serum functional antibody responses, determined by NBAA, were significantly higher in subjects in the vaccine group compared to placebo. VP1 specific IgA was significantly increased in nasal secretions and saliva in the vaccine group. Protective efficacy for prevention of NVG was 21% (p= 0.149) and for NV infection was 29% (p= 0.003). An 85% decrease in geometric mean viral shedding in stool in the VXA-G1.1-NN group was also observed. Totality of evidence analysis for all 6 outcomes simultaneously provided a z-score of 5.56 (p< 0.001), indicating protective benefit of VXA-G1.1-NN.Figure 3.Cellular and serum immune responses following vaccination with VXA-G1.1-NN or placebo Conclusion VXA-G1.1-NN was safe, immunogenic, and reduced both viral shedding and NV infection following NV challenge. VXA-G1.1-NN tableted vaccine may help limit outbreaks by reducing viral shedding. Totality of evidence analysis for treatment effect provided a strong statistical signal supporting a protective effect of VXA-G1.1-NN. Disclosures Susan Greco, MD, MPH, Vaxart, Inc: Stocks/Bonds (Public Company) Becca A. Flitter, PhD, MPH, Vaxart Inc: Stocks/Bonds (Public Company) Lam Nguyen, MD, CVS Health: Stocks/Bonds (Public Company)|Vaxart: Author is either employed and/or has received stock options from Vaxart as part of this work.|Vaxart: Stocks/Bonds (Public Company) Darreann Carmela Hailey, MS, Bionano Genomics: Stocks/Bonds (Public Company)|Vaxart, Inc.: Stocks/Bonds (Public Company) Sean N. Tucker, PhD, Vaxart, Inc.: Grant/Research Support|Vaxart, Inc.: patent|Vaxart, Inc.: Ownership Interest|Vaxart, Inc.: Stocks/Bonds (Public Company) James F. Cummings, MD, VAXART: Stocks/Bonds (Public Company)

IPNV Inactive Vaccine Supplemented with GEL 02 PR Adjuvant: Protective Efficacy, Cross-protection, and Stability.

Recently, outbreaks of infectious pancreatic necrosis (IPN) in worldwide rainbow trout farms caused by IPN virus (IPNV) strains belonging to genogroup 1 and genogroup 5 are reported. In this study, formaldehyde-inactivated vaccines supplemented with or without GEL 02 PR adjuvant were developed by using both genogroups IPNV strains and were intraperitoneally injected into rainbow trout. At 30 days post-vaccination, the viral loads of IPNV challenged rainbow trout (Oncorhynchus mykiss) in the vaccine groups were significantly decreased compared with those in the PBS group (P < 0.05), about 2.4 log and 2.5 log in the genogroup 1 and 5 IPNV inactivated vaccine with or without GEL 02 PR adjuvant groups, and the protective effect was not weakened after storage of the adjuvant vaccines at 4 °C for 12 months. Each vaccine could stimulate the expression of CD4, CD8, and IgM, and the adjuvant vaccines induced higher neutralizing antibody titers. In the long-term protection test, both the adjuvant vaccines could still effectively reduce IPNV viral loads in fish at 120 days post-vaccination, and the genogroup 5 IPNV inactivated vaccine showed cross-protection against the genogroup 1 IPNV strain. In the study of cell lines and virus seeds, CHSE-214 was successively passaged to 30 generations, and its growth characteristics and sensitivity to IPNV remained stable. When IPNV was passaged to 10 generations, the viral titers were not affected, but mutations were found in the VP2 protein of both genogroup 1 and 5 IPNV strains. The study is conducive to the improvement of IPNV vaccine development for rainbow trout.

P-721. Risk Factors Associated with COVID-19 Among Fully Vaccinated Healthcare Workers in Lima, Peru

Abstract Background Healthcare workers (HCWs) are an important target group for COVID-19 vaccination. In February 2021, Peru launched a COVID-19 vaccination campaign among HCWs using a BBIBP-CorV inactivated whole-virus vaccine (Sinopharm). We aim to understand risk factors for SARS-CoV-2 infection after vaccination using a cohort of HCWs in two hospitals in Lima, Peru. Methods Between August 2021-June 2022, HCW who received at least two COVID-19 Sinopharm vaccine doses were enrolled in the cohort and followed for 6 months. Participants provided a self-collected nasal swab weekly for SARS-CoV-2 by reverse transcriptase polymerase chain reaction testing. SARS-CoV-2 infection was confirmed by a positive PCR test result at least 14 days after receiving the second vaccine dose. Adjusted hazard ratios (aHR) were used to identify associations with infection accounting for potential confounding. Person-time was calculated based on days between negative PCR results, capped at 10 days; in cases of infection, the time between positive and negative tests was halved, with half the days considered at risk. Results Of 670 vaccinated HCWs, 111 (16.6%) tested positive for SARS-CoV-2 during the follow-up period. In adjusted models, prior report of COVID-19 illness in the previous 12-months was associated with reduced risk of infection (aHR: 0.98 [95% CI:0.97‒0.99], p=0.026). Being beyond 6 months since the last vaccination was significantly associated with an increased risk of infection (aHR: 3.22 [95% CI:1.66‒6.23], p=0.0001) as well as working in an outpatient setting (aHR: 1.94 [95% CI:1.06‒3.53], p=0.031). Conclusion In this cohort of healthcare workers undergoing regular asymptomatic COVID testing, our findings suggest evidence of waning protection at 6 months post-vaccination BBIBP- CorV. Additionally, preliminary indications suggest that healthcare worker behaviors or specific occupational exposures may contribute to increased infection risk even following vaccination. In addition, these results support the inclusion of HCWs as a priority group for additional booster doses of COVID-19 vaccine at 6 months after the most recent dose. Disclosures All Authors: No reported disclosures

593. Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of the Safety of BPL-1357, A BPL-Inactivated, Whole-Virus, Universal Influenza Vaccine

Abstract Background Better influenza vaccines are needed, not just for seasonal strains but for future pandemic viruses. BPL-1357 is a whole-virus, β-propiolactone-inactivated vaccine containing four wild-type, low-pathogenicity avian influenza viruses (H1N9, H3N8, H5N1, and H7N3). In mice and ferrets, BPL-1357 provided robust protection against challenge with a diverse set of influenza A viruses, including completely heterosubtypic strains. Methods A phase 1, randomized, placebo-controlled, double-blinded, study was performed in volunteers 18 to 55 years of age using a single dose-level of vaccine given twice 28-days apart, either intramuscularly (IM) or intranasally (IN). Forty-five participants were block randomized (1:1:1) to receive IM BPL-1357 and IN placebo (IM group), IM placebo and IN BPL-1357 (IN group), or IM placebo and IN placebo (placebo group). Adverse events (AEs) were solicited using a questionnaire for 7 days after each vaccination and volunteers had medical follow-up for 182 days after the second vaccine (V2D182). Solicited AEs were presented visually as proportions. AEs were compared using tests of proportions at day 28 (V2D28) and V2D182. Results Forty-five participants were enrolled between June 27, 2022 and November 9, 2022 and randomized into each group (n=15,15,15). Two participants (placebo group) delayed or missed their second dose because they developed COVID-19. No serious AEs were observed. Most AEs were mild. Injection site pain was the most common AE, which occurred in 87%/67% of the IM group after each vaccine dose respectively, but only in 33%/0% of the IN group, and 13%/21% of the placebo group. Other AEs, such as fatigue and headache, were similarly observed across the three groups. There was a severe AE possibly related to the IN vaccine (fever 39-40°C) which occurred after the first dose, but not the second. When comparing intervention-related AEs, only injection site pain was found to occur more frequently in the combined IM+IN group relative to placebo. Conclusion BPL-1357 was safe and well-tolerated. Pain at the injection site was commonly seen in the IM group, though was mostly mild. Other AEs were similar in frequency between vaccine and placebo groups. Further work to determine the immunogenicity and efficacy of BPL-1357 is underway. Disclosures All Authors: No reported disclosures

P-1395. Safety and Effectiveness of LC16m8 for Pre-Exposure Prophylaxis Against mpox in High-Risk Population: An Open-Label Randomized Trial

Abstract Background Since May 2022, the incidence of mpox cases has surged outside endemic regions. Although vaccination remains pivotal in mpox prevention, data on LC16m8, a third-generation smallpox vaccine, are scant. We provided LC16m8 pre-exposure prophylaxis opportunities to high-risk individuals, including those with HIV, and conducted a randomized controlled trial to assess LC16m8’s effectiveness in mpox prevention and safety. Methods Our multicenter randomized open-label trial enrolled men and women aged ≥18 years at high mpox risk who provided written consent. Participants were randomly assigned 1:1 to early or late vaccination groups, receiving vaccinations approximately 70 days apart. Primary endpoint: vaccine effectiveness (VE) against mpox development between early and late vaccinations. VE against severe mpox, symptoms, “take” incidence, and adverse events were secondary endpoints. Results A total of 1,135 participants were recruited; 570 and 565 were assigned to early and late vaccination groups, respectively; 530 and 476 were vaccinated. Median age: 41 years; 99.7% were male; 89.7% Japanese; and 34.4% HIV-infected. No mpox cases occurred during the observation period, precluding VE calculation. “Take” rates: 90.3% (HIV-infected), 94.6% (uninfected). Adverse events related to the study were observed in 96.6% and 98.0% of the HIV-infected and uninfected participants, respectively. No fatal adverse events were observed; serious adverse events (SAE): 0.6% (HIV-infected), 0.5% (uninfected). One HIV-uninfected participant reported pulmonary embolism and deep vein thrombosis as a causally undeniable SAE. Local skin reactions: 96.6% (HIV-infected), 97.9% (uninfected); systemic reactions: 63.6% (HIV-infected), 64.2% (uninfected). Conclusion LC16m8’s effectiveness in mpox prevention remains inconclusive. Yet, its use in well-controlled HIV-infected and -uninfected individuals showed no significant safety concerns, suggesting potential for targeted vaccination strategies in at-risk groups. Disclosures All Authors: No reported disclosures

Safety evaluation of tetravalent meningococcal conjugate vaccine in combination with the inactivated poliomyelitis vaccine and diphtheria-tetanus-acellular pertussis vaccine for infants

Objective: To investigate the safety of the tetravalent meningococcal conjugate vaccine (MPCV-ACYW) in combination with the inactivated poliomyelitis (IPV) vaccine and diphtheria-tetanus-acellular pertussis (DTaP) vaccine for infants aged 3-5 months and provide real-world evidence for the immunization strategy of vaccine combination. Methods: From June to October 2023, a total of 600 3-month-old infants were selected and divided into three groups: control group, mono-vaccination group and combined vaccination group. They were simultaneously or individually vaccinated with MPCV-ACYW, IPV and DTaP vaccines at 3, 4, and 5 months of age, respectively. The incidence rate of adverse reactions within 30 days after each dose was observed. Results: All 600 infants completed at least one vaccination and entered the safety data analysis. The age of the control group (100 infants), the mono-vaccination group (250 infants), and the combination group (250 infants) was (101.20±7.88), (102.26±7.94), and (102.35±7.76) days, respectively. The body lengths were (63.00±3.02), (62.55±3.06), and (63.14±4.02) cm, respectively. The body weights were (6.90±0.77), (6.86±0.94), and (6.99±0.95) kg, respectively. Boys accounted for 49%, 50.4%, and 52.4%, respectively, with no statistically significant differences (all P>0.05). The overall incidence rates of adverse reactions in the control group, mono-vaccination group, and combined vaccination group were 4.00%, 2.80%, and 3.20%, respectively, with systemic adverse reaction rates of 3.00%, 2.40%, and 2.00%. The incidence rates of local adverse reactions were 1.00%, 0.40%, and 1.20%, with no statistically significant differences (all P>0.05). Adverse reactions were mainly grade 1, with incidence rates of grade 1 adverse reactions of 3.00%, 2.00%, and 1.60% in the three groups, and incidence rates of grade 2 adverse reactions of 1.00%, 0.80%, and 1.60%, respectively. No grade 3 or 4 serious adverse reactions occurred, and the differences were not statistically significant (all P>0.05). The adverse reaction symptoms of the three groups were mainly systemic reactions, among which fever and diarrhea symptoms were reported in individual cases in each group, with no statistically significant differences in the incidence rate (all P>0.05). The symptoms of adverse reactions were mostly transient and self-relieved, all of which were cured. Conclusion: The combination of MPCV-ACYW and IPV or DTaP vaccines is safe for infants aged 3-5 months.

Differential expression of vascular endothelial growth factor A (VEGFA) and M1 macrophage marker nitric oxide synthase 2 (NOS2) in lymph node granulomas of BCG-vaccinated and non-vaccinated cattle infected with Mycobacterium bovis.

Bovine tuberculosis is mainly caused by Mycobacterium bovis. Bacillus Calmette-Guérin (BCG) is an attenuated strain of M. bovis which provides variable disease protection. Lesions have been characterized in infected cattle, but little comparison has been done with lesions which form in BCG-vaccinates. Here, in situ hybridization examined differences in expression of M. bovis RNA, inducible nitric oxide synthase 2, and vascular endothelial growth factor A in relation to vaccination status and granuloma grade, using two different groups of cattle. Data found no differences between vaccination groups or granuloma grade in average copies of M. bovis mRNA per μm2 of total granuloma area or per μm2 of necrotic areas. Within a vaccination group high-grade granulomas had more NOS2 per cell, per μm2 and a higher percentage of cells expressing NOS2 than low-grade granulomas. Non-vaccinates had a higher percentage of cells producing NOS2 than vaccinates. Differences in NOS2 expression varied by group. Vaccination status and granuloma grade did not affect the average copies of VEGFA per cell or the percent of cells expressing RNA, however VEGFA copies per μm2 varied between groups. These findings suggest NOS2 and VEGFA are likely not mechanisms of BCG vaccination protection but may impact disease severity.

Beta-variant recombinant SARS CoV-2 vaccine induces durable cross-reactive antibodies against Omicron BA variants

BackgroundWe previously reported the safety and immunogenicity data from a randomized trial comparing the booster responses of vaccinees who received monovalent (MV) recombinant protein Beta-variant (MVB.1.351) and MV ancestral protein (MVD614) vaccines with AS03 adjuvant (Sanofi/GSK) to booster response of vaccinees who received mRNA MV ancestral strain BNT162b2 vaccine (Pfizer-BioNTech).MethodsFirst booster of the vaccines was administered in adult participants previously primed with 2 doses of MV ancestral strain BNT162b2. A subset of these participants with available blood samples collected at Day 0 (D0), at 28 days (D28), and 3 months (M3) post-booster were contacted for additional testing (195/208 participants). The persistence of cross-neutralizing antibodies, including against Omicron BA.1 and BA.4/5, up to 3 months after boosting was evaluated using a validated pseudovirus neutralization assay.ResultsAcross the whole population, MVB.1.351 vaccine induces highest NAbs titers against Omicron BA.1 and BA.4/5 variants at D28 and M3 post-booster. In participants with SARS-CoV-2 infection between D28 and M3, both MVB.1.351 and BNT162b2 vaccine groups show an increase in GMTs against Omicron BA.1 and Omicron BA.4/5 following infection. Among uninfected participants, the ratio of M3 to D28 GMTs was higher for the MVB.1.351 group than the BNT162b2 group against Omicron BA.1 (0.64 [0.53;0.77] versus 0.43 [0.35;0.53]), Omicron BA.4/5 (0.61 [0.50; 0.75] versus 0.44 [0.34; 0.56]), and D614 (0.68 [0.58,0.81] versus 0.46 [0.39,0.55]).ConclusionsThe MVB.1.351 vaccine induces higher and durable cross-neutralizing antibodies against Omicron subvariants up to 3 months after boosting compared to an MV ancestral and mRNA BNT162b2 booster vaccine.

Cellular and humoral immune responses in cats vaccinated with feline herpesvirus 1 modified live virus vaccine.

Feline herpesvirus 1 (FHV-1) is an important pathogen causing infectious rhinotracheitis in felids, mainly infecting the upper respiratory tract and conjunctiva. Multiple vaccines are available to prevent FHV-1 infection, and the antibody levels are always used to evaluate their effectiveness. However, the cellular immunity response following immunization in cats remains unclear. This study investigated the immune responses (humoral and cellular) in cats immunized with the FHV-1 modified live virus vaccine. The results indicated that vaccination significantly reduced clinical signs, and antibody levels, including virus-neutralizing (VN) antibodies and immunoglobulin G (IgG), in the vaccine group were higher than those in the control groups. Additionally, the vaccine significantly increased cytokine secretion, indicating Th1-type cellular immune responses in cats. Moreover, cellular immune-related indicators, such as CD8+ T cells, CD4+ T cells, and interferon-gamma levels, were inversely correlated with clinical signs post-challenge by FHV-1 in vaccinated cats, highlighting its crucial role in protecting cats against FHV-1 infection. In summary, this study demonstrated the importance of cellular immune responses in protecting cats from FHV-1 infection after vaccination.

Comparison of Long-Term Antibody Titers in Calves Treated with Different Conjunctival and Subcutaneous Brucella abortus S19 Vaccines.

Brucellosis is still the most common zoonosis worldwide despite advanced technology and animal husbandry. Since there is still no effective Brucella vaccine for humans, it is crucial to control the disease in ruminants through eradication and vaccination. Although some countries around the world have achieved this circumstance, every country aims to become free of Brucellosis through vaccination, animal movements, and various eradication measures. For this purpose, the Brucella abortus S19 strain has been used safely for about 100 years. However, due to the O-polysaccharide (OPS) antigen in its structure, the antibody response created by the vaccine causes confusion in serological tests. For this purpose, researchers have provided both mucosal immunity and short-term antibody response by using the B. abortus S19 vaccine in conjunctival form instead of subcutaneous form. This study aimed to determine how long the post-vaccination titer levels persisted in animals vaccinated with vaccines from 3 different companies and different routes. In this study, a total of 115 calves aged 3 to 4.5 months were created in five groups, with 23 animals in each group: group 1 (vaccine brand A), group 2 (vaccine brand B), and group 3 (vaccine brand C) received the two-dose conjunctival vaccine, group 4 received the single-dose subcutaneous vaccine (vaccine brand C), and group 5 received the subcutaneous vaccine (vaccine brand C) plus the booster dose conjunctival vaccine (vaccine brand B). Brucellosis antibody titers were monitored each 21 days until the cattle were 26-28 months old. The collected sera were analyzed using the Rose Bengal Plate Test (RBPT), Serum Agglutination Test (SAT), and Complement Fixation Test (CFT), which are the preferred serological methods for Brucellosis eradication plans worldwide. In the conjunctival vaccination groups, only 3 (13%) of the animals in group 1 developed antibody titers one month after vaccination, and there was no antibody response detected against Brucellosis in group 2 and group 3. In animals that were stimulated conjunctivally, the threshold value of 30 International CFT Units (ICFTUs) (for distinguishing between infective titers and vaccination titers) was observed in one animal each in group 1 and group 2 and 0 animal in group 3. It was found that antibody titers turn to Brucellosis negative in all conjunctival vaccine groups at 7 months after vaccination. In groups 4 and 5, the first-month serological screening detected over 30 ICFTUs in 17 (89.47%) animals and 16 (69.5%) animals, respectively. In group 4, CFT titers were found to fall below 30 on the 17th month and 9.3 on the 22nd month. On the 14th month, the CFT titers of group 5 were found to be below 30, and all animals in this group turned negative after the 19th month. It was found that the single dose B. abortus S19 subcutaneous vaccination in calves caused persistent antibodies in 5% of the population. It is believed that persistent and high antibody titers created by subcutaneous vaccines will cause false positivity and create confusion in Brucellosis eradication programs. Therefore, although there is no clear distinction between vaccinated and infected animals, it has been observed that conjunctival Brucellosis vaccines create more stable antibody titers and decrease rapidly compared to subcutaneous vaccines. Based on the results of this study and the advantages of conjunctival vaccines, more effective eradication programs and antibody monitoring can be carried out in vaccinated herds where Brucellosis outbreaks are observed.

The Association Between COVID-19 Vaccination Uptake and Information-Seeking Behaviors Using the Internet: Nationwide Cross-Sectional Study.

The COVID-19 pandemic, declared in March 2020, profoundly affected global health, societal, and economic frameworks. Vaccination became a crucial tactic in combating the virus. Simultaneously, the pandemic likely underscored the internet's role as a vital resource for seeking health information. The proliferation of misinformation on social media was observed, potentially influencing vaccination decisions and timing. This study aimed to explore the relationship between COVID-19 vaccination rates, including the timing of vaccination, and reliance on internet-based information sources in Japan. Using a cross-sectional study design using a subset of panel data, this nationwide survey was conducted in 7 waves. A total of 10,000 participants were randomly selected through an internet survey firm, narrowing down to 8724 after applying inclusion and exclusion criteria. The primary outcome was the COVID-19 vaccination date, divided into vaccinated versus unvaccinated and early versus late vaccination groups. The main exposure variable was the use of internet-based information sources. Control variables included gender, family structure, education level, employment status, household income, eligibility for priority COVID-19 vaccination due to pre-existing medical conditions, and a health literacy scale score. Two regression analyses using generalized estimating equations accounted for prefecture-specific correlations, focusing on vaccination status and timing. In addition, chi-square tests assessed the relationship between each information source and vaccination rates. Representing a cross-section of the Japanese population, the regression analysis found a significant association between internet information seeking and higher vaccination rates (adjusted odds ratio [aOR] 1.42 for those younger than 65 years; aOR 1.66 for those aged 65 years and older). However, no significant link was found regarding vaccination timing. Chi-square tests showed positive associations with vaccination for television, government web pages, and web news, whereas blogs and some social networking sites were negatively correlated. Internet-based information seeking is positively linked to COVID-19 vaccination rates in Japan, underscoring the significant influence of online information on public health decisions. Nonetheless, certain online information sources, including blogs and some social networks, negatively affected vaccination rates, warranting caution in their use and recognition. The study highlights the critical role of credible online sources in public health communication and the challenge of combating misinformation on less regulated platforms. This research sheds light on how the digital information landscape influences health behaviors, stressing the importance of accurate and trustworthy health information amidst global health emergencies.

Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness.

We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.

CD40 Ligand Potentiates Immunogenecity of Mycoplasma pneumoniae Subunit Vaccine Candidate in a Murine Model.

Mycoplasma hyopneumoniae (Mhp) infection severely affects the daily weight gain and feed-to-meat ratio of pigs, while secondary infections with other pathogens can further lead to increased mortality, causing significant economic losses to the pig industry. CD40L is a molecular adjuvant that enhances the cellular and humoral immune responses to vaccines. In this study, the CD40L peptide was fused to the C-terminus of the chimeric P97R1P46P42 protein by genetic engineering using the pFastBac Dual vector. The recombinant chimeric protein P97R1P46P42 and its fusion P97R1P46P42-CD40L were expressed in Sf9 cells and purified. Mice were immunized with P97R1P46P42 or its fusion protein. Seppic ISA 201 emulsified protein, conventional Mhp vaccine and PBS control groups were included. Immunogenecity was assessed by specific IgG antibody response, splenic lymphocyte proliferation, and cytokine IL-4 and IFN-γ levels. We found that CD40L fusion significantly enhanced specific antibody response, lymphocyte proliferation and IL-4 level in the immunized mouse sera as compared to the P97R1P46P42 or conventional vaccine group. This study provides clear evidence that CD40L potentiates the humoral and cellular immune responses to the Mhp chimeric protein P97R1P46P42 in the mouse model. This CD40L-fused chimeric protein could be a MPS subunit vaccine candidate to be tested for its efficacy in pigs in response to challenges with pathogenic Mycoplasma hyopneumoniae strain(s).

Evaluating the effect of the antiPCSK9 vaccine on systemic inflammation and oxidative stress in CFA-challenged albino mice.

To investigate whether the antiPCSK9 vaccine can affect the CRP and oxidative stress (OS) during acute systemic inflammation. Male albino mice were randomly divided into three groups: non-treated mice (the sham group), treated with a nonspecific stimulator of the immune response - Freund's complete adjuvant (CFA; the CFA group), and vaccinated mice treated with CFA (the vaccine group). The vaccine group was subcutaneously immunized with the antiPCSK9 formulation, 4 × in bi-weekly intervals. To induce inflammation, all mice were subjected to the CFA challenge after the vaccination plan. The hsCRP level and OS status were evaluated by a mouse CRP ELISA kit and the pro-oxidant antioxidant balance (PAB) assay, respectively. The vaccine induced a high-titter IgG antiPCSK9 antibody, which was accompanied with a significant PCSK9 reduction (-24.7% and -28.5% compared with the sham and CFA group, respectively), and the inhibition of PCSK9/LDLR interaction (-27.8% and -29.4%, respectively). hsCRP was significantly increased in the vaccine and CFA groups by 225% and 274% respectively, when compared with the sham group; however, it was non-significantly decreased (-18%; p = 0.520) in the vaccine group in comparison with the CFA group. The PAB values indicated that OS was significantly increased in the CFA group (by 72.7%) and the vaccine group (by 76%) when compared to the sham group; however, there was no significant difference in the PAB values between the vaccine and CFA groups. The antiPCSK9 vaccine failed to significantly reduce the serum hs-CRP and OS induced in the CFA-challenged albino mice.