Pre-vaccination Levels Research Articles

Enhanced Antimicrobial Peptide Response Following Bacillus Calmette-Guerin Vaccination in Elderly Individuals.

Antimicrobial peptides are an important component of host defense against Mycobacterium tuberculosis. However, the ability of BCG to induce AMPs as part of its mechanism of action has not been investigated in detail. We investigated the impact of Bacillus Calmette-Guerin (BCG) vaccination on circulating plasma levels and TB-antigen stimulated plasma levels of AMPs in a healthy elderly population. We assessed the association of AMPs, including Human Beta Defensin 2 (HBD-2), Human Neutrophil Peptide 1-3 (HNP1-3), Granulysin, and Cathelicidin (LL37), in circulating plasma and TB-antigen stimulated plasma (using IGRA supernatants) at baseline (pre-vaccination) and at Month 1 and Month 6 post vaccination. Post BCG vaccination, both circulating plasma levels and TB-antigen stimulated plasma levels of AMPs significantly increased at Month 1 and Month 6 compared to pre-vaccination levels in the elderly population. However, the association of AMP levels with latent TB (LTB) status did not exhibit statistical significance. Our findings indicate that BCG vaccination is linked to heightened circulating levels of AMPs in the elderly population, which are also TB-antigen-specific. This suggests a potential mechanism underlying the immune effects of BCG in enhancing host defense against TB.

Comparison of anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination in hospital staff

Multiple concerning reports have emerged of cardiovascular complications, particularly thrombosis, following mRNA vaccination against the SARS-CoV-2 pathogen. The presence of serologically persistent anti-phospholipid antibodies is a characteristic of antiphospholipid syndrome, which presents with clinical manifestations including thrombosis or pregnancy morbidity. Anti-SARS-CoV-2 mRNA vaccines pose a theoretical risk of cross-reactivity between the SARS-CoV-2 spike protein and phospholipids in host tissues. In this study, serum anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination were compared among 184 hospital staff members. Although no significant differences were found in terms of antibody titers targeting cardiolipin and β2-glycoprotein I, post-vaccination antibody titers targeting phosphatidylethanolamine were found to be significantly increased compared to pre-vaccination levels (p = 0.008). Anti-phosphatidylethanolamine antibodies are the most common anti-phospholipid antibodies detected in patients with recurrent miscarriages at < 10 weeks of gestation. However, the association between vaccination and these types of adverse events remains unknown, thus warranting further investigation.

Trained Immunity Generated by the Recombinant Zoster Vaccine.

Trained immunity may play a role in vaccine-induced protection against infections. We showed that the highly efficacious recombinant VZV-gE zoster vaccine (RZV) generated trained immunity in monocytes, natural killer (NK) cells, and dendritic cells (DCs) and that the less efficacious live zoster vaccine did not. RZV stimulated ex vivo gE-specific monocyte, DC and NK cell responses that did not correlate with CD4 + T-cell responses. These responses were also elicited in purified monocyte and NK cell cocultures stimulated with VZV-gE and persisted above prevaccination levels for ≥ 4 years post-RZV administration. RZV administration also increased ex vivo heterologous monocyte and NK cell responses to herpes simplex and cytomegalovirus antigens. ATAC-seq analysis and ex vivo TGFβ1 supplementation and inhibition experiments demonstrated that decreased tgfβ1 transcription resulting from RZV-induced chromatin modifications may explain the development of monocyte trained immunity. The role of RZV-trained immunity in protection against herpes zoster and other infections should be further studied.

Impact of HIV-Related Immune Impairment of Yellow Fever Vaccine Immunogenicity in People Living with HIV-ANRS 12403.

The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.

A Low Number of Baselines γδ T Cells Increases the Risk of SARS-CoV-2 Post-Vaccination Infection.

Background: The COVID-19 pandemic is the biggest global health problem in the last hundred years. The efficacy of the vaccine to protect against severe disease is estimated to be 70-95% according to the studies carried out, although there are aspects of the immune response to the vaccine that remain unclear. Methods: Humoral and cellular immunity after the administration of three doses of the Pfizer-BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 were studied. SARS-CoV-2 IgG and IgA antibodies, αβ and γδ T-cell subsets, and their differentiation stages and apoptosis were analyzed. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the duration of the study. This increase was the greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+ CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to a γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: The results unveil the important role of γδ T cells in SARS-CoV-2-vaccine-mediated protection from the disease.

Long-Term Dynamic Changes in Hybrid Immunity over Six Months after Inactivated and Adenoviral Vector Vaccination in Individuals with Previous SARS-CoV-2 Infection.

Numerous studies have largely focused on short-term immunogenicity in recovered individuals post mRNA vaccination. However, understanding the long-term durability, particularly in inactivated and adenoviral vectored vaccines, remains limited. We evaluated antibody responses, omicron variant neutralization, and IFN-γ responses in 119 previously infected individuals vaccinated with CoronaVac or ChAdOx1 up to six months post-vaccination. Both vaccines elicited robust immune responses in recovered individuals, surpassing those who were infection-naïve, and these persisted above pre-vaccination levels for six months. However, antibody levels declined over time (geometric mean ratio (GMR) = 0.52 for both vaccines). Notably, neutralizing activities against omicron declined faster in ChAdOx1 (GMR = 0.6) compared to CoronaVac recipients (GMR = 1.03). While the first dose of ChAdOx1 adequately induced immune responses in recovered individuals, a second dose demonstrated advantages in omicron variant neutralization and slower decline. Although both vaccines induced T cell responses, the median IFN-γ level at six months returned to pre-vaccination levels. However, more individuals exhibited reactive T cell responses. Extending the interval (13-15 months) between infection and vaccination could enhance antibody levels and broaden neutralization. Together, these findings demonstrate a robust humoral and cellular response that was sustained for at least six months after vaccination, thus guiding optimal vaccination strategies based on prior infection and vaccine platforms.

Immunological aspects of vaccination in HIV-infected patients

Until recently, HIV infection does not lose its relevance. In 2022, 630 000 people died and 1.3 million people became infected with the human immunodeficiency virus (HIV). HIV-positive persons develop more infectious diseases than healthy people do; the causative agents are mainly opportunistic microorganisms. Streptococcus pneumoniae is the main causative agent of infection in the lungs in HIV-infected persons. In order to prevent the development of severe pneumococcal infections and to overcome antibiotic resistance, vaccines have been developed. There are polysaccharide (PPV) and conjugate (PCV) vaccines. According to clinical recommendations, vaccination of previously unvaccinated HIV-infected patients is carried out regardless of T-helper cell level. However, no data were found on the effect of PCV13 on immunological memory cells. The purpose of this study is to assess an effect of PCV13 vaccination on the immune system in HIV-infected subjects.&#x0D; Materials and methods. The study included 200 patients with HIV infection, which were divided into two groups: I — received a dose of PCV13 (n = 100) and control group (n = 100). During the first visit, immunological and microbiological studies were carried out. On the second visit, a PCV13 was injected into the deltoid muscle. The third visit was made a year later, where immunological and microbiological studies were repeated. Participants were divided into 4 subgroups depending on CD4+ T cell level. The microbial study was done using a swab collected from the back of the throat.&#x0D; Results. During the immunological examination at visit 1, abnormalities were detected in all examined populations and immune cell subsets. At 12 months post-vaccination, the median levels of CD3+CD4+ and CD45RO+ T lymphocytes in the immunized group were higher than pre-vaccination levels compared to control group, in which the values changed insignificantly. Our data confirm the immunological effectiveness of PCV13 administration in HIV-infected patients. In patients with peripheral blood CD19+ lymphocyte deficiency, had increased microbial detection rate (p = 0.003).&#x0D; Conclusion. As a result, due to the high risk of pneumococcal pneumonia, HIV-infected patients should be immunized with a 13-valent pneumococcal conjugate vaccine.

Twenty-Month Monitoring of Humoral Immune Response to BNT162b2 Vaccine: Antibody Kinetics, Breakthrough Infections, and Adverse Effects.

Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were (i) to observe the humoral immune response to the BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), (ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and (iii) to determine the adverse effects after primary vaccine doses. To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

The effect of nurses’ COVID-19 vaccination status on fear of COVID-19: A cross-sectional study

ABSTRACT Aims The aim of this study is to determine the effect of nurses' COVID-19 vaccination status on fear of COVID-19. Methods The research was conducted as a descriptive, correlational and cross-sectional study. A personal information form and the Fear of COVID-19 Scale were used for data collection. Data were collected using an online questionnaire. Descriptive statistics, t-test and ANOVA were used to evaluate the data. Results The pre-vaccine and post-vaccine COVID-19 fear levels of the nurses were moderate. It was found that nurses who were women, were older, had a longer working period, and had COVID-19 experienced significantly higher fear. The vaccination rate was found to be 52.8%. When vaccination status and COVID-19 fear levels were evaluated, it was determined that vaccinated nurses had a significantly higher mean pre-vaccine fear score (p < .05). It was observed that the mean COVID-19 fear score decreased significantly after vaccination. Discussion The findings of this study showed that vaccination has an effect on the fear of COVID-19, that vaccination is important and that studies in this area need to be increased.

Baseline HMGB-1 Concentrations Are Predictive of Neutralization Efficacy after SARS-CoV-2 mRNA Vaccination

Abstract Determining vaccine efficacy in individuals is a concern when managing the spread of a virus. In this study pre-vaccination levels of a panel of inflammation factors were measured in order to predict the efficacy of the SARS-CoV-2 mRNA vaccines by measuring neutralization percentages, SARS-CoV-2 antibody concentrations, and inflammation factors over the course of ten weeks after the initial dose of the mRNA vaccine. Blood and stool samples were collected at a time point before administration of the vaccine (pre-vaccination) and in 2-week intervals after the administration of the first dose (post-vaccination). A cohort of 12 adults (n=12) were separated into two groups, high neutralization ability (n=6) and low neutralization ability (n=6), based on the neutralization percentages measured from samples provided ten weeks post-vaccination. Bivariate correlation analysis was performed to measure correlation between the panel of inflammation factors measured from pre-vaccination samples and neutralization ability at ten weeks post-vaccination. Correlation analysis indicates a significant (P=0.0321) inverse relationship (R =−0.5269) between HMGB-1 concentrations and neutralization ability at time points ten weeks post-vaccination. Unpaired t-test between the high and low neutralization groups and HMGB-1 concentrations taken pre-vaccination are also significantly different (P&amp;lt;0.001). Preliminary results indicate that HMGB-1 is a promising biomarker in predicting SARS-CoV-2 mRNA vaccine efficacy. This study was supported in part by funding provided by Hawaii Community Foundation under award 20HCF-101573. The comments expressed in this report are the sole responsibility of the authors and do not represent the official view of the Hawaii Community Foundation.

Effect of COVID-19 vaccine on blood glucose metrics in Arabic people with type 1 diabetes.

People with diabetes are at a higher risk for coronavirus disease-19 (COVID-19) and hence are prioritized for vaccination. The aim of the current study was to investigate the effects of COVID-19 vaccination on blood glucose control in Arabic people with type 1 diabetes (T1D). Secondary aim was to compare the responses between the two vaccines approved for use in Kuwait. This retrospective study compared ambulatory glucose metrics, using a continuous glucose monitoring device, measured for 14 days before, and 7 days and 14 days after, the first and second dose of the COVID-19 vaccine in Arabic people with Type 1 diabetes (T1D). We also explored possible links with vaccine type and other clinical characteristics. Glucose metrics calculated were time in range (TIR, 3.9-10 mmol/L), time above range (TAR, 10.1- 13.9 mmol/L or >13.9 mmol/L), time below range (TBR, 3- 3.9 mmol/L or <3 mmol/L) and glucose variability (CV). We enrolled 223 participants in the study. Over the 7 days period after the first vaccination dose there was a decrease in TIR (mean difference (SD) -1.9% ± 14.8%; p = 0.05) and increase in TAR >10 mmol/L (2.2% ± 15.9%; p = 0.04), with no effects on TBR. These effects were not seen after the second dose or 14 days after either dose. There was a decrease in CV over the 7 days period after the first (-1.2% ± 7.4%; p = 0.02) and second vaccine doses (-1.1% ± 6.9%; p = 0.03), with no effects noted 14 days after either dose. In subgroup analysis similar effects on TIR and TAR were also seen in those who had received the viral vector-based vaccine, but not the mRNA-based vaccine, although the decrease in CV was seen in those who had received the mRNA based vaccine but not the viral vector-based vaccine. We found a temporary impairment in glucose control in the first 7 days, particularly among individuals receiving viral vector vaccines. The group receiving mRNA vaccine was likely to experience an increase in glucose levels above the target range. However, the temporary change in metrics appears to return to pre-vaccination levels after one-week post-vaccination. The effects on glycemic parameters were more neutral after the second dose.

Post-Vaccination and Post-Infection Immunity to the Hepatitis B Virus and Circulation of Immune-Escape Variants in the Russian Federation 20 Years after the Start of Mass Vaccination.

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018-2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018-2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination.

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.

The Impact of Sputnik SARS-CoV-2 Vaccines on Antibody Response in the Egyptian Population

BACKGROUND: The coronavirus disease 2019 (COVID-2019) causes the severe contagious acute respiratory syndrome. Therefore, massive vaccination campaign is mandatory to control the spread. Sputnik COVID-19 vaccines induce immunity through different mechanisms involving antibody response that bind to the spike protein to neutralize the viral entry into the cells. AIM: This study aims to compare the titers of specific antibodies in the pre- and post-vaccination sera in the vaccinated Egyptian population to evaluate the efficacy of the sputnik vaccine. METHODS: Samples were collected from 205 adult volunteers receiving the Sputnik vaccine in the Reference Laboratory of Egyptian University Hospitals. Samples were collected before vaccination and within 1, 2, or 3 months after receiving two doses of Sputnik SARS-CoV-2 vaccines from August to October 2021, serum samples collected were tested by quantitative chemiluminescent immunoassay using (Mindray CL-960i chemiluminescence analyzer, India) at the Reference laboratory of Egyptian University Hospitals for neutralizing antibodies, anti-spike antibodies, and total antibody levels before and after vaccination. RESULTS: The results of the 205 paired samples illustrated that there was a statistically significant difference between pre- and post-vaccination antibody levels with a p-value of (&lt; 0.001) indicating that the vaccine produced significantly high levels of antibodies. CONCLUSION: COVID-19 Sputnik vaccines induce immunity through an antibody response that binds to the virus to neutralize its entry into cells. Our study showed a significant increase in the measured post-vaccination levels of the three antibodies among the enrolled volunteers compared to the basal pre-vaccination level and thus sputnik vaccine protects against SARS-CoV-2 infections.

96. A Candidate Respiratory Syncytial Virus (RSV) Prefusion F Protein Investigational Vaccine (RSVPreF3 OA) Is Immunogenic when Administered in Adults ≥ 60 Years of Age: Results at 6 Months after Vaccination

Abstract Background RSV infections are frequent and can lead to respiratory complications in older adults (OA). However, there is no licensed RSV vaccine yet. Here we present immunogenicity results up to month (M) 6 after vaccination with the RSVPreF3 OA. Methods In this phase 3 multi-country ongoing study (NCT04732871), adults ≥ 60 years of age were randomized (3:1:1) to receive RSVPreF3 OA and to be followed up for 3 years. All participants received a dose of RSVPreF3 on day (D) 1. Humoral immune (HI) and cell-mediated immune (CMI) responses were measured in subsets of participants at pre-vaccination (D1), D31 and M6. HI outcomes included RSV-A and RSV-B neutralizing antibody (NAb) geometric mean titers (GMTs) and RSVPreF3-specific immunoglobulin G (IgG) antibody geometric mean concentrations (GMCs). The CMI response was assessed in terms of frequency of RSVPreF3-specific CD4+ T-cells and CD8+ T-cells expressing at least 2 activation markers including at least 1 cytokine among CD40L, 4-1BB, IL-2, TNF-α, IFN-γ, IL-13, IL-17 (polypositive T-cells). Results A total of 1653 participants received a dose of RSVPreF3 OA. Of these, 987 participants were included in the HI subset and 566 in the CMI subset at D1. The RSV-A and RSV-B GMTs and RSVPreF3-specific IgG GMCs increased between D1 and D31 followed by a decline until M6. At D31, RSV-A and RSV-B NAb GMTs were 10.5-fold and 7.8-fold higher than pre-vaccination (Figure), and RSVPreF3-specific IgG antibody GMCs was 12.2-fold higher than pre-vaccination levels. At M6, the RSV-A and RSV-B GMTs were 4.4-fold and 3.5-fold, and RSVPreF3-specific IgG antibody GMCs were 4.7-fold above pre-vaccination levels. The RSVPreF3-specific polypositive CD4+ T-cell median frequency (events/106 cells) increased from 191 (below assay quantification limit) to 1339 at D31 and declined to 666 (above assay quantification limit) by M6. No RSVPreF3-specific CD8+ T-cell response was detected after RSVPreF3 OA vaccination. Conclusion In adults ≥ 60 years of age, 1 dose of RSVPreF3 OA was shown to be immunogenic, with both high HI and specific CMI responses at D31 post-vaccination and remained 3.5–4.7 fold above pre-vaccination levels at M6. This study will continue to monitor the immunogenicity of RSVPreF3 OA up to 3 years. Funding GlaxoSmithKline Biologicals SA. Disclosures Tino F. Schwarz, Prof. Dr. MD, Biogen, Merck-Serono, Pfizer, Alexion, Bavarian Nordic, Janssen-Cilag, AstraZeneca, Biontech, MSD: Grants|GlaxoSmithKline Biologicals SA: Honoraria John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Charles Andrews, MD, GlaxoSmithKline Biologicals SA: Institutional grant|Merck and Boehringer Ingelheim: Consulting fees outside of the submitted work Delphine Collete, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Magali de Heusch, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Nathalie De Schrevel, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Ownership Interest Bruno Salaun, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Marc Lievens, MSc, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Céline Maréchal, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Phoebe Nakanwagi, Master’s in Biostatistics, GlaxoSmithKline Biologicals SA: Employee Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.

584. Prospective Observational Cohort Study of Serological Responses to COVID-19 Vaccines in Pediatric Kidney Transplant Recipients at a Single Institution

Abstract Background Pediatric kidney transplant recipients (PKTR) are at risk of poor outcomes from COVID-19. Data on serologic responses to COVID-19 vaccines in PKTR remain sparse. We characterized the magnitude, breadth, and longevity of SARS-CoV-2 spike protein binding antibody responses in PKTR. Methods This single institution, prospective observational study enrolled PKTR presenting to a transplant clinic for routine care who had received or were eligible to receive a COVID-19 vaccine. Demographic data, history of prior COVID-19, and vaccination details were collected. Plasma samples obtained from standard-of-care residual specimens were analyzed for SARS-CoV-2 spike variant IgG using the MesoScale Discovery V-PLEX platform, which quantitatively measures antibodies to SARS-CoV-2 full-length spike wild-type (Wuhan-hu-1), Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529; BA.1) variants. Vaccine time points with &amp;gt; 5 samples available were analyzed. Geometric mean titers (GMTs) were calculated and log-transformed titers were compared using one-way ANOVA with Tukey’s post-hoc comparisons test. Results 61 PKTR enrolled (Table1); 47 (77%) received at least 1 dose of COVID-19 vaccine in transplant clinic. 47 (77%) PKTR had at least one sample available for analysis, but serial specimens were lacking for many. By 6 months post-dose 2 of COVID-19 mRNA vaccination, spike (Wuhan-hu-1) IgG titers had waned to pre-vaccination levels (GMT 24 vs 47 binding antibody units (BAU)/mL, P=0.988). Administration of a 3rd dose of mRNA vaccine significantly boosted IgG antibodies (GMT 492 BAU/mL, P=0.007), and titers were maintained at 3 months (GMT 656 BAU/mL, P=0.001) but gradually waned by 6 months (GMT 223 BAU/mL, P=0.070). Administration of a 4th dose elicited a non-significant increase in titers (GMT 905 BAU/mL, P=0.870). Binding IgG antibodies to SARS-CoV-2 variant spike proteins post-vaccination were not significantly different from Wuhan spike. Conclusion In this cohort of PKTR, a 3rd dose of COVID-19 mRNA vaccine significantly boosted broadly cross-reactive binding IgG antibodies to SARS-CoV-2 spike variants, including Omicron. Decreasing titers at 6 months post-dose 3 raise concern for waning protective immunity and support 4th dose vaccination. Disclosures Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc: Data Safety Monitoring Board|MedImmune: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Grant/Research Support|Micron: Grant/Research Support|NIH: Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines|PaxVax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data Adjudication and Data Safety Monitoring Boards|WCG and ACI Clinical: Data Adjudication Board Andi L. Shane, MD, MPH, MSc, International Scientific Association for Probiotics and Prebiotics (ISAPP): Honoraria Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur.: Grant/Research Support|Meissa Vaccines, Inc.: Co-inventor of RSV vaccine technology licensed to Meissa Vaccines, Inc.|NIH (Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines): Grant/Research Support.

Multi-trial analysis of HIV-1 envelope gp41-reactive antibodies among global recipients of candidate HIV-1 vaccines.

Many participants in HIV-1 vaccine trials, who have not previously been exposed to or vaccinated against HIV-1, display serum immunoglobulin antibodies that bind the gp41 region of HIV-1 envelope prior to vaccination. Previous studies have hypothesized that these pre-existing antibodies may be cross-reactive and may skew future vaccine responses. In 12 large studies conducted by the HIV Vaccine Trial Network (HVTN) (n=1470 individuals), we find wide variation among participants in the pre-vaccine levels of gp41-reactive antibodies as measured by the binding antibody multiplex assay (BAMA). In the absence of exposure to the gp41 immunogen, anti-gp41 IgG levels were temporally stable over 26-52 weeks in repeated measures of placebo recipients. The analysis revealed that the geometric mean of pre-vaccine anti-gp41 IgG response was greater among participants in South Africa compared with participants in the United States. With gene-level metagenomic sequencing of pre-vaccination fecal samples collected from participants in one trial (HVTN 106), we detected positive associations between pre-vaccine anti-gp41 IgG and abundance of genes from multiple taxa in the Eubacteriales order. The genes most strongly associated with higher baseline anti-gp41 IgG mapped to a clade containing Blautia wexlerae and closely related strains. In trials with vaccine products containing the full or partial portion of gp41 immunogen alongside a gp120 immunogen, we did not find evidence that individuals with higher baseline anti-gp41 IgG had different levels of anti-gp120 IgG after vaccination compared to individuals with lower pre-vaccine anti-gp41 levels (pooled estimate of standardized mean difference -0.01 with a 95% CI [-0.37; 0.34]).

Decline of humoral immune responses after natural SARS-CoV-2 infection can be efficiently reversed by vaccination.

Our aim was to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody level kinetics after coronavirus disease 2019 (COVID-19) infection and determine the efficiency of vaccination on SARS-CoV-2-specific antibody levels. The study included 50 SARS-CoV-2 infected and 70 uninfected cases. Levels of SARS-CoV-2-specific IgG nucleocapsid protein (IgG-NP), IgG spike protein (IgG-SP), IgM nucleocapsid protein (IgM-NP), and IgA spike protein (IgA-SP) antibodies were evaluated by an enzyme-linked immunosorbent assay in sera obtained at baseline, 1st, 3rd, and 6th month follow-up visits for infected cases and at postvaccination visits for all cases. In symptomatic cases (n = 50), IgG-SP levels were decreased in 6 months compared with baseline, while IgA-SP levels were significantly increased. IgG-NP levels were significantly decreased in symptomatic cases at the 6-month visit. After vaccination, IgG-SP levels were increased in symptomatic cases compared with prevaccination levels. Among subjects vaccinated with CoronaVac (the Sinovac COVID-19 vaccine), infected cases had approximately double the IgG-SP level of uninfected cases. SARS-CoV-2-specific antibody levels were higher at the baseline in symptomatic cases. Nevertheless, all infected cases showed significantly reduced IgG-SP levels at the 6th month. Vaccination effectively increased IgG-SP levels.

Prevaccination Glycan Markers of Response to an Influenza Vaccine Implicate the Complement Pathway.

A key to improving vaccine design and vaccination strategy is to understand the mechanism behind the variation of vaccine response with host factors. Glycosylation, a critical modulator of immunity, has no clear role in determining vaccine responses. To gain insight into the association between glycosylation and vaccine-induced antibody levels, we profiled the pre- and postvaccination serum protein glycomes of 160 Caucasian adults receiving the FLUZONE influenza vaccine during the 2019–2020 influenza season using lectin microarray technology. We found that prevaccination levels of Lewis A antigen (Lea) are significantly higher in nonresponders than responders. Glycoproteomic analysis showed that Lea-bearing proteins are enriched in complement activation pathways, suggesting a potential role of glycosylation in tuning the activities of complement proteins, which may be implicated in mounting vaccine responses. In addition, we observed a postvaccination increase in sialyl Lewis X antigen (sLex) and a decrease in high mannose glycans among high responders, which were not observed in nonresponders. These data suggest that the immune system may actively modulate glycosylation as part of its effort to establish effective protection postvaccination.

Emotional Reaction to the First Dose of COVID-19 Vaccine: Postvaccination Decline in Anxiety and Stress among Anxious Individuals and Increase among Individuals with Normal Prevaccination Anxiety Levels.

Although vaccination has been adopted by the WHO to limit worldwide transmission of COVID-19, people’s worries about COVID-19 vaccines may suppress their desire for vaccination despite vaccine availability. This study aimed to investigate anxiety and stress symptoms among 250 Jordanians (mean age = 43.18 ± 6.34 years, 72% females) who received their first vaccine dose. The respondents completed the anxiety and stress subscales of the Depression Anxiety and Stress scale 21 (DASS-21) before and after vaccination. The respondents expressed more moderate–severe levels of stress before than after vaccination (20.8% and 13.2%, respectively). Meanwhile, 37.2% and 45.2% of the respondents expressed moderate–severe anxiety before and after vaccination, respectively. Wilcoxon signed-rank test revealed that the drop in the level of stress from before- (median (IQR) = 5 (1–8)) to after vaccination (median (IQR) = 3 (1–7)) was statistically significant (z = −3.81, p = 0.001, r = 0.17) while the increase in anxiety was not. Anxiety significantly dropped postvaccination among individuals experiencing mild to severe anxiety before vaccination. Similarly, stress and anxiety significantly increased among individuals expressing normal anxiety before vaccination (z = −3.57 and −8.24, p values = 0.001, r = 0.16 and 0.37, respectively). Age positively correlated with postvaccination anxiety among respondents with mild prevaccination anxiety, and it negatively correlated with the prevaccination level of stress in the normal-anxiety group. Gender, marital status, respondents’ level of education, and history of COVID-19 infection had no significant correlation with anxiety or stress at either point of measurement. Overcoming their hesitancy to receive COVID-19 vaccines, individuals with normal levels of anxiety experienced a rise in their distress symptoms following immunization. On the contrary, vaccination seemed to desensitize anxious individuals. Policymakers need to formulate a population-specific plan to increase vaccine preparedness and promote psychological well-being over all during the pandemic.