Post-vaccination Titers Research Articles

The effectiveness of the organization and specific prevention of Rh-conflict during pregnancy

AIM: The aim of the study was to evaluate the effectiveness of the organization and medical provision of complex specific antenatal and postpartum prevention of primary isoimmunization with domestic anti-Rh0(D) immunoglobulin in Rh-negative women.
 MATERIALS AND METHODS: To achieve the goal, an algorithm for managing pregnancy in Rh-negative women was developed, complex antenatal and postpartum prophylaxis of primary isoimmunization with anti-Rh0(D) immunoglobulin was carried out, and its effectiveness was evaluated in 37 women who gave birth to Rh-positive newborns. If antibodies to the Rh0(D) antigen were not detected, then at 28 weeks pregnant women were administered human immunoglobulin anti-Rh0(D) at a dose of 1500 IU (300 g). Anti-Rh0(D) antibody titer was monitored every 23 weeks before delivery. Mothers were re-introduced with human anti-Rh0(D) immunoglobulin at a dose of 1500 IU (300 g) within 2472 hours after the birth of an Rh-positive child. 6 months after delivery, the antibody titer to the Rh0(D) antigen was re-determined.
 RESULTS: After the introduction of domestic human immunoglobulin anti-Rh0(D), side effects and allergic reactions were not registered. All 37 (100%) women were delivered at term, of which 7 (18.9%) were delivered abdominally. All newborns were born with an Apgar score of 89 without hemolytic disease. The titer of antibodies to the Rh0(D) antigen was negative in 24 (64.9%) women 6 months after delivery. 13 (35.1%) mothers had a post-vaccination antibody titer not higher than 1 : 2, which is allowed by the instructions for the anti-Rh0(D) human immunoglobulin preparation. They tested negative again 12 months after delivery.
 CONCLUSION: The results of the study showed a rather high efficiency of the organization and medical provision of complex specific antenatal and postpartum prevention of primary isoimmunization with domestic anti-Rh0(D) immunoglobulin in Rh-negative women.

Influence of the Single Nucleotide Polymorphisms rs12252 and rs34481144 in IFITM3 on the Antibody Response after Vaccination against COVID-19.

The COVID-19 mRNA vaccine is the first mRNA vaccine approved for human administration by both the U.S. Food and Drug Administration and the European Medicines Agency. Studies have shown that the immune response and the decay of immunity after vaccination with the COVID-19 vaccines are variable within a population. Host genetic factors probably contribute to this variability. In this study, we investigated the effect of the single-nucleotide polymorphisms rs12252 and rs34481144 in the interferon-induced transmembrane protein (IFITM) 3 gene on the humoral immune response after vaccination against COVID-19 with mRNA vaccines. Blood samples were collected from 1893 healthcare workers and medical students at multiple time points post-vaccination and antibody titers against the SARS-CoV-2 S1 protein receptor binding domain were determined at all time points. All participants were genotyped for the rs34481144 and rs12252 polymorphisms in the IFITM3 gene. After the second and third vaccinations, antibody titer levels increased at one month and decreased at six months (p < 0.0001) and were higher after the booster vaccination than after the basic immunization (p < 0.0001). Participants vaccinated with mRNA-1273 had a higher humoral immune response than participants vaccinated with BNT162b2. rs12252 had no effect on the antibody response. In contrast, carriers of the GG genotype in rs34481144 vaccinated with BNT162b2 had a lower humoral immune response compared to A allele carriers, which reached statistical significance on the day of the second vaccination (p = 0.03) and one month after the second vaccination (p = 0.04). Further studies on the influence of rs12252 and rs34481144 on the humoral immune response after vaccination against COVID-19 are needed.

COVID-19 Vaccine Seroresponse Based on The Timing of The Primary Series; Pre- versus Post-Renal Transplantation.

Coronavirus disease 2019 (COVID-19) poses a serious risk to patients with chronic kidney disease (CKD) and renal transplant. While COVID-19 vaccination is recommended before transplant, there are limited data comparing vaccine timing. Our aim is to evaluate serological responses to COVID-19 vaccines pre- and post-renal transplant and the durability of antibody levels. We retrospectively evaluated the antibody response of adult renal transplant recipients who had received at least a primary series of the COVID-19 vaccine. The patients were divided into two groups based on the timing; pre- or post-transplant. Antibody titer levels were evaluated at least 4weeks after vaccination for each group. Titer durability was assessed by calculating the median titer level of individuals. A total of 139 patients were identified between January 2019 and April 2022. Twenty-nine patients were excluded because of previous COVID-19 infection, and 15 patients were excluded each for insufficient vaccine doses and lack of titer data. Forty patients were included for the pre-transplant group and 40 for post-transplant. The number of pre-transplant patients who developed antibodies (39 patients, 97.5%) was significantly greater than the number of post-transplant patients (21 patients, 52.5%) with p<.01. The median post-vaccination titer levels were significantly greater in the pre-transplant group up to 5months after vaccination (p<.05). The pre-transplant group's titers seemed sustained even after renal transplantation. Vaccinating renal transplant patients before transplant results in increased achievement of seroresponse, higher levels of antibody titers, and sustained titers following transplant. Larger and prospective studies are warranted to confirm the findings.

Non-protective immunity after standard pneumococcal vaccination series identified as a potential contributing risk factor for refractory otolaryngologic conditions in children.

To examine the relationship between conferred immunity after standard pneumococcal series and refractory otolaryngologic infections in pediatric patients using post-vaccination antibody titers, and to identify contributory underlying conditions revealed when vaccination/re-vaccination fails to confer protective immunity. IRB-reviewed and "exempt" retrospective case series with chart review using the Epic® Electronic Medical Record system from 2013 to 2021. Dedicated tertiary referral children's hospital. Pneumococcal antibody titer results were assessed for children ages 0 to 21 years and: (1) at least 1 of 7 otolaryngologic disease diagnoses and (2) having received the 4-dose schedule of pneumococcal conjugate vaccine (PCV 7 or 13). A total of 241 subjects met inclusion criteria with 356 laboratory tests. Recurrent acute otitis media, chronic rhinitis, and chronic otitis media with effusion were the 3 most frequent diagnoses. At presentation, only 27.0% of subjects had titers conferring immunity from their prior vaccinations with PCV. About 85 subjects had been subsequently revaccinated with Pneumococcal Polysaccharide Vaccine (PPSV), and antibody responses conferring immunity reached 91.8%. Seven subjects never developed adequate responses; 5 of these had recurrent acute otitis media as the primary otolaryngologic diagnosis. Secondary "revealed" diagnoses included Juvenile Rheumatoid Arthritis (n = 1), unresolved specific antibody deficiency (n = 2), and Hypogammaglobulinemia (n = 1). In pediatric patients with recurrent infectious otolaryngologic disease refractory to traditional medical and surgical therapy, inadequate responses to pneumococcal vaccination may be revealed. This correlation represents a potential pathway for diagnosis and therapy.

The Impact of Body Mass Index on the Antibody Titer after Astra Zeneca Vaccination at UTA’45 Vaccine Center

Background: AstraZeneca is the viral vector vaccine. This vaccine has a more advanced method that uses a modified virus to trigger antibodies to fight the Covid-19 virus. Objective: To evaluate the impact of Body Mass Index on the Antibody Titer after AstraZeneca Vaccination atUTA'45 Vaccine Center. Method: Cross-sectional prospective method was used in this study with a convenience sampling design. Only participants who signed the informed consent were included in this study. Results: The results of the P-value on the comparison of Gender and BMI are 0.36 which indicates a correlation between BMI and Gender, also in BMI and age (the P-Value of the comparison of age and BMI was 0.57) BMI plays an important role in the comparison of these factors. BMI is one of the factors that influence the development of antibodies after vaccination. Antibody titer 2 is significantly affected by BMI, the correlation between BMI and antibody titer 2 is very significant ( P-Value 0,000). Conclusion: Based on this study, it was found that there was a correlation between Age, Gender, and BMI on Antibody Titer after AstraZeneca vaccination. However, the correlation between Age and Gender to BMI is not very significant, the presence of factors can still affect Antibody Titers. In addition, it can also be concluded that there is a very significant correlation between antibody titer 2 (post-vaccination antibody titer) and a person's BMI. This is shown from the results of the P-Value of 0.000.

The impact of full-fat Hermetia illucens larvae meal on the health and immune system function of broiler chickens.

Alternative protein sources have recently been attracting growing interest as potential components of livestock nutrition. This study evaluated the effect on broiler health of replacing the soybean protein component of poultry feed with processed insect protein from farmed Hermetia illucens (HI) larvae. A total of 384 male broiler chicks were divided into four diet groups (eight pens/treatment and 12 birds/pen) and reared to the 42nd day of life (dol). Each treatment group received a starter diet until the 14th dol, then a grower diet until the 35th and finally a finisher diet until the 42nd. The soybean meal in standard diets was replaced with full-fat HI larvae meal in the following amounts: 0% for the control group HI-0, 50% for group HI-50, 75% for group HI-75, and 100% for group HI-100. At 1 dol, chicks were vaccinated against Marek's disease, coccidiosis, Newcastle disease and infectious bronchitis and at 7 dol against avian metapneumovirus infections using live-attenuated vaccines. Blood and spleen samples were collected at three and six weeks of age and analysed using ELISA, flow cytometry, haematology and biochemistry. On the 42nd dol, as the content of larvae meal in the chickens' diets increased, the birds' body weights decreased significantly. The substitution of the protein source had no effect on the haematological markers. In chicks that received larvae meal, there was a decrease in creatine kinase activity and phosphorus levels and an increase in calcium and uric acid levels in serum. Raising the proportion of full-fat HI larvae meal in the diet raised the percentage of T CD3+CD8a+ cells and lowered that of T CD3+CD4+ cells in both sample types. Chickens fed larvae meal had significantly lower post-vaccination anti-infectious bronchitis virus antibody titres. The poorer production results and impaired health in experimental birds may indicate lower than 50% protein substitution with full-fat HI larvae meal to be optimal.

Immunogenicity of quadrivalent meningococcal conjugate vaccine in frequent platelet donors

AbstractFrequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women’s Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/μL and 34% with ≤350/μL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.

Sex and age differences in B cell frequencies and antibody responses following influenza vaccination in highly vaccinated adult populations

Abstract Annual influenza vaccination is required for healthcare workers (HCWs, 18–49 years of age) at Johns Hopkins and is highly recommended to older adults (75+ years of age) to limit severe outcomes from annual influenza. As a result, vaccination rates and pre-vaccination immunity are high in both populations. We previously reported that sex differences in vaccine-induced antibody responses are not observed in these highly vaccinated populations, but that age-associated reductions in antiviral immunity following vaccination are more pronounced in males than females against both H1N1 and H3N2 viruses. Here, we conducted a clinical study of immune responses to the quadrivalent influenza vaccine to evaluate sex and age differences in influenza A vaccine (IAV) B cell including CD19+ B, plasmablasts (PB, CD3 −CD19 +CD38 ++CD71 +CD20 −IgD −H1 +H3 +), memory B cells (MB, CD3 −CD19 +CD71 −IgD −H1 +H3 +), and age-associated B cells (CD3 −CD19 +CD21 −CD11c −T-bet +H1 +H3 +) following receipt of the seasonal influenza vaccine in 2019–2020 and 2021–2022 seasons among male and female young adult HCWs and older adults. Both young and older females consistently have more total and IAV CD19+ B cells than males, with the greatest percentage being H1. Older adults, however, consistently have greater frequencies of IAV MB cells than young adults. Even with these cellular differences, males and females have equivalent post-vaccination neutralizing antibody titers against H1 and H3 influenza viruses. Whether the transcriptional profiles of B cells differ based on sex and age is currently under investigation. Taken together, these studies may provide mechanistic insights into variability in vaccine outcomes and protection based on the sex and age of the individual. U54AG062333

Immunogenicity and safety of fractional doses of 17D-213 yellow fever vaccine in HIV-infected people in Kenya (YEFE): a randomised, double-blind, non-inferiority substudy of a phase 4 trial

Evidence indicates that fractional doses of yellow fever vaccine are safe and sufficiently immunogenic for use during yellow fever outbreaks. However, there are no data on the generalisability of this observation to populations living with HIV. Therefore, we aimed to evaluate the immunogenicity of fractional and standard doses of yellow fever vaccine in HIV-positive adults. We conducted a randomised, double-blind, non-inferiority substudy in Kilifi, coastal Kenya to compare the immunogenicity and safety of a fractional dose (one-fifth of the standard dose) versus the standard dose of 17D-213 yellow fever vaccine among HIV-positive volunteers. HIV-positive participants aged 18-59 years, with baseline CD4+ T-cell count of at least 200 cells per mL, and who were not pregnant, had no previous history of yellow fever vaccination or infection, and had no contraindication for yellow fever vaccination were recruited from the community. Participants were randomly assigned 1:1 in blocks (variable block sizes) to either a fractional dose or a standard dose of the 17D-213 yellow fever vaccine. Vaccines were administered subcutaneously by an unblinded nurse and pharmacist; all other study personnel were blinded to the vaccine allocation. The primary outcome of the study was the proportion of participants who seroconverted by the plaque reduction neutralisation test (PRNT50) 28 days after vaccination for the fractional dose versus the standard dose in the per-protocol population. Secondary outcomes were assessment of adverse events and immunogenicity during the 1-year follow-up period. Participants were considered to have seroconverted if the post-vaccination antibody titre was at least 4 times greater than the pre-vaccination titre. We set a non-inferiority margin of not less than a 17% decrease in seroconversion in the fractional dose compared with the standard dose. This study is registered with ClinicalTrials.gov, NCT02991495. Between Jan 29, 2019, and May 17, 2019, 303 participants were screened, and 250 participants were included and vaccinated; 126 participants were assigned to the fractional dose and 124 to the standard dose. 28 days after vaccination, 112 (96%, 95% CI 90-99) of 117 participants in the fractional dose group and 115 (98%, 94-100) of 117 in the standard dose group seroconverted by PRNT50. The difference in seroconversion between the fractional dose and the standard dose was -3% (95% CI -7 to 2). Fractional dosing therefore met the non-inferiority criterion, and non-inferiority was maintained for 1 year. The most common adverse events were headache (n=31 [12%]), fatigue (n=23 [9%]), myalgia (n=23 [9%]), and cough (n=14 [6%]). Reported adverse events were either mild (182 [97%] of 187 adverse events) or moderate (5 [3%]) and were self-limiting. Fractional doses of the 17D-213 yellow fever vaccine were sufficiently immunogenic and safe demonstrating non-inferiority to the standard vaccine dose in HIV-infected individuals with CD4+ T cell counts of at least 200 cells per mL. These results provide confidence that fractional dose recommendations are applicable to populations with high HIV prevalence. Wellcome Trust, Médecins Sans Frontières Foundation, and the UK Department for International Development.

Humoral Response in Hemodialysis Patients Post-SARS-CoV-2 mRNA Vaccination: A Systematic Review of Literature.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has infected over 600 million individuals and caused nearly 7 million deaths worldwide (10 January 2023). Patients with renal disease undergoing hemodialysis are among those most adversely affected, with an increased predisposition to SARS-CoV-2 infection and death. This systematic review aimed to pool evidence assessing the humoral response of hemodialysis patients (HDP) post-mRNA SARS-CoV-2 vaccination. A systematic search of the literature was performed through MEDLINE, CINAHL, PubMed, EMBASE, and Web of Science databases, as well as medRxiv and bioRxiv preprint servers up to 10 January 2023. Cohort and case-control studies were included if they reported an immune response in one group of patients undergoing hemodialysis who received mRNA SARS-CoV-2 vaccination compared with another group of patients receiving the same vaccine but not on hemodialysis. The methodological quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was not deemed appropriate due to the high heterogeneity between studies. From the 120 studies identified, nine (n = 1969 participants) met the inclusion criteria. Most studies (n = 8/9, 88%) were of high or medium methodological quality (≥6/9 stars). The results revealed that HDP developed lower antibody levels across all timepoints post-vaccination when compared with controls. Patients with chronic kidney disease elicited the highest antibody immune response, followed by HDP and, lastly, kidney transplant recipients. Overall, post-vaccination antibody titers were comparatively lower than in the healthy population. Current results imply that robust vaccination strategies are needed to address waning immune responses in vulnerable populations.

A170 ADVERSE EVENTS &amp; SEROLOGICAL RESPONSES FOLLOWING SARS-COV-2 VACCINATION IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE

Abstract Background The rapid development and distribution of SARS-CoV-2 vaccines has raised concerns surrounding vaccine safety in immunocompromised populations, such as those with inflammatory bowel disease (IBD). Purpose We described adverse events (AEs) following SARS-CoV-2 vaccination in those with IBD and determined relationships between AEs to post-vaccination antibody titres. Method Individuals with IBD from a prospective cohort in Calgary, Canada (n=670) who received a 1st, 2nd, 3rd, and/or 4th dose of a SARS-CoV-2 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were interviewed via telephone for AEs using the Adverse Events Following Immunization form. Subsequently, we assessed injection site reaction as a specific AE outcome. Multivariable logistic regression models were used to assess the association between anti-SARS-CoV-2 spike protein antibody (anti-S) levels within 1–12 weeks of vaccination and injection site reaction following 1st, 2nd, and 3rd dose vaccination. Models were adjusted for age, sex, IBD type, IBD medications, vaccine type, and prior COVID-19 infection. Additionally, we evaluated the risk of flare of IBD within 30 days of vaccination via chart review. Result(s) Table 1 describes AEs in individuals with IBD following 1st dose (n=331), 2nd dose (n=331), 3rd dose (n=195), and 4th dose (n=100) of a SARS-CoV-2 vaccine. AEs were reported in 83.3% of participants after 1st dose, 79.1% after 2nd dose, 77.4% after 3rd dose, and 67.0% after 4th dose. Injection site reaction (pain, redness, etc.) was the most common AE (50.8% of AEs), with fatigue and malaise (18.1%), headache and migraine (8.6%), musculoskeletal discomfort (8.2%), and fever and chills (6.5%) also commonly reported. Multivariable logistic regression determined no associations between anti-S concentration and injection site reaction for all doses. Age above 65 years was associated with decreased injection site reaction following 1st and 3rd doses, while female sex and mRNA vaccine type were associated with increased injection site reaction following 1st and 2nd doses. Prior COVID-19 infection, IBD type, and medication class were not associated with injection site reaction with any dose. Only one participant was diagnosed with a severe AE requiring hospitalization: Immune thrombocytopenic purpura (ITP) following 2nd dose of a Pfizer vaccination. No cases of IBD flare occurred within 30 days of vaccination. Image Conclusion(s) AEs following SARS-CoV-2 vaccination are generally mild and become less common with each consecutive dose. Antibody levels following each dose of the vaccine were not associated with injection site reactions. Females, those under 65 years of age, and those administered mRNA vaccines were more likely to experience an injection site reaction. Prior COVID-19 infection, IBD type, and IBD medication class did not predict injection site reactions. Vaccination was not associated with IBD flare within 30 days of vaccination. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Helmsley Disclosure of Interest A. Markovinovic: None Declared, M. Herauf: None Declared, J. Quan: None Declared, L. Hracs: None Declared, J. Windsor: None Declared, N. Sharifi: None Declared, S. Coward: None Declared, L. Caplan: None Declared, J. Gorospe: None Declared, C. Ma Grant / Research support from: Ferring, Pfizer, , Consultant of: AbbVie, Alimentiv, Amgen, Ferring, Pfizer, Takeda, , Speakers bureau of: AbbVie, Alimentiv, Amgen, Ferring, Pfizer, Takeda, R. Panaccione Grant / Research support from: AbbVie, Ferring, Janssen, Pfizer, Takeda, Consultant of: Abbott, AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pandion Pharma, Pfizer, Progenity, Protagonist, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Takeda, Theravance, UCB, Speakers bureau of: AbbVie, Arena, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, Takeda, R. Ingram: None Declared, J. Kanji: None Declared, G. Tipples: None Declared, J. Holodinsky: None Declared, C. Berstein Grant / Research support from: AbbVie, Amgen, Janssen, Pfizer, Takeda, Speakers bureau of: AbbVie, Janssen, Pfizer, Takeda, D. Mahoney: None Declared, S. Bernatsky: None Declared, E. Benchimol: None Declared, G. Kaplan Grant / Research support from: Ferring, Speakers bureau of: AbbVie, Janssen, Pfizer

Successful restoration of protective immunity against measles, mumps, and rubella following MMR vaccination in adult hematopoietic cell transplant recipients.

The optimal number of doses as well as the role for measurement of postvaccination titers after measles, mumps, rubella (MMR) vaccination in adult hematopoietic cell transplantation (HCT) recipients remains unknown. In the present study, we assessed humoral immunity against measles, mumps and rubella before and after MMR vaccination in 187 adults who received at least one dose of the MMR vaccine after HCT. Among those with baseline titers, posttransplant prevaccination seroprotection rates were 56%, 30%, and 54% for measles, mumps, and rubella, respectively; and significantly lower in allogeneic versus autologous HCT recipients for measles (39%vs. 80%, p = .0001), mumps (22%vs. 41%; p = .02) and rubella (48%vs. 62%, p = .12). Among those who were seronegative at baseline, seroconversion rates after one dose of MMR were 69%, 56%, and 97% for measles, mumps, and rubella, respectively. Seronegative patients after one dose of MMR (i.e., nonresponders) seroconverted for measles and mumps after a second MMR vaccine dose. Our findings demonstrate successful restoration of protective immunity against measles, mumps, and rubella after vaccination in adult HCT recipients; one dose of MMR elicited protective titers in the majority of patients, and a second vaccine dose was immunogenic in nonresponders.

The Effect of Antipyretics on Antibody Production in Pediatric Patients Post-Vaccination

The COVID-19 pandemic and subsequent vaccine administration renewed the question of the potential effect that antipyretics have on antibody levels post-vaccination in pediatric patients. Many patients take antipyretics to reduce side effects and fevers as they have anti-inflammatory properties. We reviewed the literature for studies examining the question of whether the consumption of antipyretics reduced post-vaccination antibody titers. We found that there is a correlation between antipyretics decreasing antibody production in the pediatric population when given prophylactically. However, to confirm these results more in depth studies are required. Our PICO question allowed us to narrow our focus into the pediatric population, antipyretic intervention, and antibody levels. Our results reflect a significant decrease in antibody levels, but antipyretics do not affect clinical efficiency of the vaccines. Our world relies on vaccine technology and it has allowed us to survive pandemics like the COVID 19 outbreak. In order to keep using these innovations safely, more trials must be conducted.

Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination

Prospective population-based studies investigating associations between reactive symptoms following SARS-CoV-2 vaccination and serologic responses to vaccination are lacking. We therefore conducted a study in 9003 adults from the UK general population receiving SARS-CoV-2 vaccines as part of the national vaccination programme. Titres of combined IgG/IgA/IgM responses to SARS-CoV-2 spike (S) glycoprotein were determined in eluates of dried blood spots collected from all participants before and after vaccination. 4262 (47.3%) participants experienced systemic reactive symptoms after a first vaccine dose. Factors associating with lower risk of such symptoms included older age (aOR per additional 10 years of age 0.85, 95% CI: 0.81–0.90), male vs. female sex (0.59, 0.53–0.65) and receipt of an mRNA vaccine vs. ChAdOx1 nCoV-19 (0.29, 0.26–0.32 for BNT162b2; 0.06, 0.01–0.26 for mRNA-1273). Higher risk of such symptoms was associated with SARS-CoV-2 seropositivity and COVID-19 symptoms prior to vaccination (2.23, 1.78–2.81), but not with SARS-CoV-2 seropositivity in the absence of COVID-19 symptoms (0.94, 0.81–1.09). Presence vs. absence of self-reported anxiety or depression at enrolment associated with higher risk of such symptoms (1.24, 1.12–1.39). Post-vaccination anti-S titres were higher among participants who experienced reactive symptoms after vaccination vs. those who did not (P < 0.001). We conclude that factors influencing risk of systemic symptoms after SARS-CoV-2 vaccination include demographic characteristics, pre-vaccination SARS-CoV-2 serostatus and vaccine type. Participants experiencing reactive symptoms following SARS-CoV-2 vaccination had higher post-vaccination titres of IgG/A/M anti-S antibodies. Improved public understanding of the frequency of reactogenic symptoms and their positive association with vaccine immunogenicity could potentially increase vaccine uptake.

Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered as a booster to adults aged ≥59 years: A phase III randomized study

ABSTRACT This 2-stage Phase III study (NCT04142242) of a recently licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) assessed the safety and immunogenicity of a booster dose in older adults (≥59 years) primed with either MenACYW-TT or a quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immune persistence of MenACYW-TT and MPSV4 after primary vaccination was also evaluated. During Stage I, the participants administered MPSV4 (n = 165) or MenACYW-TT (n = 236) 3 years previously were randomized 9:2 to receive either a MenACYW-TT booster or to have blood drawn for persistence only. Participants primed with MPSV4 or MenACYW-TT 6–7 years previously had blood drawn for antibody persistence only. A serum bactericidal assay using human complement was used to measure functional antibodies against each serogroup at baseline and, for those receiving a booster, 30 days post-vaccination (D30). Proportions of participants with seroresponse (post-vaccination titers ≥1:16 when baseline titers <1:8 or ≥ 4-fold increase when baseline titers ≥1:8) were determined. Safety data were collected up to D30. Seroresponse rates for all serogroups at D30 ranged from 49.2% to 60.8% in the MPSV4-primed group, and 79.3–93.1% in the MenACYW-TT-primed group. MenACYW-TT induced sufficient seroresponses in each primed group. Geometric mean titers (GMTs) for serogroups C, W, and Y remained or trended higher than pre-vaccination levels at both 3 and 6–7 years after primary vaccination, indicating immune persistence. Safety outcomes were comparable between groups. A MenACYW-TT booster was immunogenic and well tolerated in participants aged ≥59 years regardless of previous quadrivalent meningococcal vaccine received. The greatest immune responses occurred in those primed with MenACYW-TT.

Safety and immunogenicity of the bi-cistronic GLS-5310 COVID-19 DNA vaccine delivered with the GeneDerm suction device

ObjectivesThe CoV2-001 phase I randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up. DesignA total of 45 vaccine-naïve participants were recruited between December 31, 2020, and March 30, 2021. GLS-5310, encoding for the SARS-CoV-2 spike and open reading frame 3a (ORF3a) proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations. ResultsGLS-5310 was well tolerated with no serious adverse events reported. Antibody and T cell responses were dose-independent. Anti-spike antibodies were induced in 95.5% of participants with an average geometric mean titer of ∼480 four weeks after vaccination and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination geometric mean titer of 28.4. T cell responses were induced in 97.8% of participants, averaging 716 site forming units/106 cells four weeks after vaccination, increasing to 1248 at week 24, and remaining greater than 1000 through 48 weeks. ConclusionGLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

A phase I clinical study to assess safety and immunogenicity of yellow fever vaccine

Yellow fever, a mosquito-borne flavivirus infection, is an important public health problem in Africa and Latin America. A Yellow Fever vaccine (YFV) was developed and tested in a study in India. This was a Phase I, open-label, randomized, controlled study where healthy adults received SII YFV intramuscularly (SII YFV IM), SII YFV subcutaneously (SII YFV SC) or STAMARIL® (Sanofi-Pasteur) in 1:1:1 ratio. They were followed for solicited reactions for 10 days and unsolicited events for 28 days and serious adverse events for 3 months. YF-neutralizing antibodies were measured at baseline and on Days 10, 14, 28. A total of 60 adults were enrolled in the study. The proportion of participants with solicited reactions was 10%, 40%, and 25% in SII YFV SC, SII YFV IM, and STAMARIL® arms, respectively. No causally related unsolicited events or any serious adverse event was reported. After vaccination, the seroconversion was 94.44%, 100%, and 100%, in the three arms respectively. The post-vaccination geometric mean titers were similar in the study arms. The new YFV was found safe and immunogenic by IM as well as SC routes. The vaccine can be tested in further phases of clinical studies.

Safety and immunogenicity of mRNA COVID-19 vaccine in inpatients with muscular dystrophy.

Due to muscular weakness and cardiopulmonary dysfunction, patients with muscular dystrophy (MD) have an increased risk of serious complications from coronavirus disease-2019 (COVID-19). Although vaccination is recommended, COVID-19 vaccination safety and immunogenicity in these patients are unknown. We investigated reaction frequency, post-vaccine antibody titers after two mRNA COVID-19 vaccine doses, and clinical predictors of antibody response among patients with MD. We recruited 171 inpatients with MD receiving two BNT162b2 mRNA COVID-19 vaccine doses from seven hospitals. Blood samples were obtained from 53 inpatients before the first dose and 28 to 30 days after the second dose, and antibody titers were measured. Overall, 104 (60.8%) and 115 (67.6%) patients had side effects after the first and second doses, respectively. These were generally mild and self-limited. Multiple logistic regression analysis showed that a bedridden state was associated with reduced side effects (odds ratio [OR] = 0.29; 95% confidence interval [CI], 0.12 to 0.71). The antibody titers of all participants changed from negative to positive after two vaccine doses. The geometric mean titer (GMT) of the inpatients was 239 (95% CI, 159.3 to 358.7). Older age (relative risk [RR]=0.97; 95% CI, 0.95 to 0.99) and bedridden state (RR=0.27; 95% CI, 0.14 to 0.51) were associated with a lower antibody titer. Patients with myotonic dystrophy type 1 (DM1) had a lower GMT than patients with other MDs (RR=0.42; 95% CI, 0.21 to 0.85). COVID-19 vaccination is safe and immunogenic in inpatients with MD. Patients with DM1 appear to have a poorer COVID-19 antibody response than those with other MDs.

638. Utility of Recombinant Hepatitis B Vaccine in Pre-liver Transplant Candidates

Abstract Background A recombinant, adjuvanted Hepatitis B (HBV) vaccine (HepB-CpG) was approved by the FDA in 2017. Initial FDA data showed greater immunogenicity than comparable recombinant HBV vaccines. Moreover, it requires only two doses over four weeks instead of three doses over six months, so there is a time advantage to HepB-CpG, which is advantageous in pre-liver transplant candidates, given their limited time before transplantation. The efficacy in this population is unknown, so we explored its efficacy This study aims to explore the efficacy of HepB-CpG in pre-liver transplant candidates, as there is currently no data on this subject. Methods This study was a retrospective review of pre-liver transplant candidates greater than 18 years old at Memorial Hermann Hospital in Houston, TX, who received at least two doses of HepB-CpG. Patients were identified from our pre-liver transplant database. Patient characteristics were collected at the time of the first dose. Vaccine efficacy was measured by anti-Hepatitis B surface antibody titers (≥10mIU/mL) at least four weeks after completion of the series. Patients who received only one dose or did not have any post-vaccine titers were excluded from the analysis. Results A total of 78 potential eligible patients were identified. After exclusion due to various reasons, a total of 27 patients were eligible for our study. Data are summarized in Table 1. Briefly, our patients were Hispanic dominant (59.3%). The median MELD score was 18, and a significant number of patients (48.1%) had underlying malignancy. The cause of cirrhosis was mainly due to alcoholic and non-alcoholic steatohepatitis (NASH). Only 13 patients (48.1%) showed seroconversion after their second dose of HepB-CpG. Moreover, of the five patients receiving immunosuppressive drugs, only one patient (20%) responded to the vaccine. Characteristics of Pre-Liver Transplant Candidates Who Had Serological Evaluation after Two Doses of Recombinant Adjuvanted Hepatitis B Vaccine. Conclusion Despite administration of HepB-CpG, less than 50% of pre-liver transplant candidates showed seroconversion. Furthermore, only one cirrhotic patient on immunosuppressive drugs responded to the vaccine. Our results illustrate the need for a better strategy to improve immunogenicity among this patient population. Larger studies are warranted to confirm the findings. Disclosures Victor I. Machicao, M.D., Gilead Inc: Advisor/Consultant.

Neutralizing and Total/IgG Spike Antibody Responses Following Homologous CoronaVac vs. BNT162b2 Vaccination Up to 90 Days Post-Booster.

We documented the total spike antibody (S-Ab), IgG S-Ab and neutralizing antibody (N-Ab) responses of BNT162b2/CoronaVac vaccinees up to 90 days post-booster dose. We included 32 homologous regimen CoronaVac vaccinees and 136 BNT162b2 mRNA vaccinees. We tested their total S-Ab (Roche), IgG (Abbott) and N-Ab (Snibe) levels at set time points from January 2021 to April 2022. All subjects were deemed to be COVID-19-naïve either via clinical history (CoronaVac vaccinees) or nucleocapsid antibody testing (BNT162b2 vaccinees). All antibodies peaked 20-30 days post-inoculation. In BNT162b2 vaccinees, all post-booster antibodies were significantly higher than second-dose peaks. In CoronaVac vaccinees, IgG showed no significant differences between peak third-/second-dose titers (difference of 56.0 BAU/mL, 95% CI of -17.1 to 129, p = 0.0894). The post-vaccination titers of all antibodies in BNT162b2 vaccinees were significantly higher than those in CoronaVac vaccinees at all time points. Post-booster, all antibodies declined in 90 days; the final total/IgG/N-Ab titers were 7536 BAU/mL, 1276 BAU/mL and 12.5 μg/mL in BNT162b2 vaccinees and 646 BAU/mL, 62.4 BAU/mL and 0.44 μg/mL in CoronaVac vaccinees. The mRNA vaccine generated more robust total S-Ab, IgG and N-Ab responses after the second and third vaccinations.