Booster Dose Research Articles

Uptake and hesitancy of the second booster dose of COVID-19 vaccine among the general population in China after the surge period of the COVID-19 pandemic: a large-scale national study

BackgroundAlthough the second booster dose of COVID-19 vaccines is available, vaccine hesitancy among the public may have peaked due to the surge in infections caused by the Omicron variant. To improve coverage of the second booster dose, it is crucial to investigate the prevalence of vaccine hesitancy among the general population during this period and explore the reasons for this phenomenon.MethodsA cross-sectional survey was conducted between January 5 to February 9, 2023. Variables including sociodemographics, mental health, COVID-19 infection status, COVID-19 vaccination status, and vaccine hesitancy were collected. Univariate and multivariate logistic regression analysis were performed to identify factors associated with the hesitancy of the second booster dose of COVID-19 vaccine among the general population.ResultsAmong the 10,623 participants, the uptake rate of the second booster dose was 4.3%. Among those who did not receive the second booster dose, 43.6% expressed vaccine hesitancy. The highest hesitancy rate was observed among participants who had not completed primary immunization (71.4%), followed by those with chronic diseases (48.6%) and those aged 60 and above (33.2%). The COVID-19 vaccine hesitancy was higher among females, participants with high incomes, those with a history of COVID-19 infection, those with depressive symptoms and post-traumatic stress disorder, and those with adverse events after COVID-19 vaccination. Conversely, lower hesitancy was observed among students, participants aged 60 and above, those from southern China, and those with higher level of perceived social support.ConclusionsCOVID-19 vaccine hesitancy remains prevalent among the general population in China after the surge period of the pandemic. Crucial steps, such as raising public awareness of the benefits and potential side effects of regular COVID-19 vaccination, ensuring timely monitoring and disclosure of pandemic information, and implementing targeted measures to improve social support and mental health, should be taken. These efforts will be instrumental in reducing vaccine hesitancy, advancing vaccination campaigns, and effectively preparing for the potential future outbreaks.

Killed whole-cell Staphylococcus aureus formulation in Montanide ISA266 and Alum adjuvants: different vaccine formulations varied in the vaccine's potency and efficacy.

Immunotherapy can be a sensible alternative because invasive Staphylococcus aureus infection mortality, morbidity, and cost are still alarmingly high despite the development of multiple new medications to treat methicillin-resistant S. aureus infections. Herein, killed whole-cell Staphylococcus aureus was formulated in Montanide ISA266 and Alum adjuvants, and the potency and efficacy of the vaccine were studied. After the preparation of two kinds of whole-cell vaccine (bacterin and lysate), 20 µg of each vaccine candidate was formulated in Montanide ISA266 and Alum adjuvants, then subcutaneously injected in distinct groups. Blood samples were taken two weeks after each booster injection, and two booster shots were given at 2-week intervals. Sera were examined by ELISA for total IgG, isotypes (IgG1 and IgG2a), and cytokine production (IFN-γ and IL-4), respectively, to ascertain the kind of induced immune response. Experimental mice were challenged intraperitoneally with 5 × 108CFU of bacteria 2 weeks after their last immunization, and the mortality rate and bacterial load were measured. Both immunogens elicited strong humoral immune responses, producing antibodies that improved opsonic capability, IFN-γ, and IL-4 production and protectivity in response to the experimental challenge. Compared to other immunized groups, the lysate formulation with Montanide ISA266 produced a greater antibody titer and IgG1 isotype and showed the highest vaccine potency. Additionally, combining the whole-cell vaccine (bacterin and lysate) with the adjuvant Montanide ISA266 increased IFN-γ and IL-4 cytokines response and protection in the experimental challenge. These findings show that avoiding S. aureus infection using active vaccination with inactivated whole-cell vaccines (bacterin and lysate) may be a successful strategy. The type of adjuvant in the vaccine formulation is important and influences vaccine potency and efficacy.

Risk of SARS-CoV-2 infection before and after the Omicron wave in a cohort of healthcare workers in Ontario, Canada

BackgroundLongitudinal healthcare worker (HCW) cohorts throughout the COVID-19 pandemic provide a unique opportunity to study the relative contributions of various exposures to infection risk over time. This study aimed to examine how demographic, health, occupational, household and community factors influenced the SARS-CoV-2 infection risk in a cohort of HCWs in Southeastern Ontario, Canada, during the early pandemic and the Omicron waves. We compared the contribution of these factors to infection risk and explored the implications for future epidemic preparedness and the protection of HCWs.MethodsWe conducted a longitudinal analysis using data from a cohort of HCWs recruited from one acute care hospital and four long-term care homes. The analysis was divided into two periods: the initial phase of the pandemic (period #1) and the first three Omicron waves (period #2). We employed Poisson regression for period #1 and Cox regression for period #2 to examine associations of demographic factors (age, sex, ethnicity, migration status, income insufficiency), health factors (chronic conditions, smoking history, SARS-CoV-2 vaccination status), household factors (exposure to COVID-19), occupational factors (work role, exposure to COVID-19 patients, personal protective equipment access, aerosol-generating procedures) and community exposures (use of masks, distance, hand-washing) with SARS-CoV-2 infection.ResultsAt period #1, 17/208 (8.2%) HCWs reported having had SARS-CoV-2 infection. At period #2, 65/167 (38.3%) reported at least one SARS-CoV-2 infection. In period #1, factors associated with increased risk of infection included working in a long-term care home, exposure to more COVID-19-positive patients, working as a nurse or therapist, and inadequate use of personal protective equipment. In period #2, the hazard of infection was higher among HCWs who had COVID-19-infected children at home, whereas the use of protective measures in the community (maintaining social distance, mask-wearing) and receiving a vaccine booster were associated with reduced risk. Providing care to COVID-19 patients was not associated with the risk of acquiring SARS-CoV-2 infection at period #2.ConclusionsDuring the Omicron wave, community and household exposures, but not occupational exposure to COVID-19 cases, were the primary factors contributing to infection risk in HCWs. This contrasts with the early waves of the pandemic where occupational exposures played a significant role. These findings may be explained by the effectiveness of institutional interventions in reducing the risk of SARS-CoV-2 transmission in healthcare settings, alongside the failure of community-level interventions to mitigate risk during the Omicron period.

Are Updated COVID-19 Vaccines Still Relevant for all Adult Age Groups? An Economic Evaluation of the Monovalent XBB.1.5 Vaccine in Australia.

There is a progressive decline in the relative effectiveness of updated COVID-19 vaccines. Surveillance reports in Australia have also shown a wide variation in the disease severity and mortality across age groups. This study aimed to perform a cost-utility analysis of the monovalent XBB.1.5 vaccine relative to no updated booster vaccine between September 2023 to August 2024. A cost-utility analysis was performed using a Markov model from the healthcare system perspective for three different age groups (18 - 64; 65 - 74; and ≥ 75 years). Costs and outcomes with the monovalent XBB.1.5 vaccine were compared to no updated booster dose for one year. Health outcomes were expressed as Quality-adjusted life-years (QALY), while costs were presented in 2023 Australian dollars. Aggregate distributional cost-effectiveness analysis and sensitivity analyses were performed. The willingness-to-pay threshold was set at AU$50,000/QALY. The updated vaccine was dominant for the 18 - 64 years group, and cost-effective for the 65 - 74 years group (incremental cost-effectiveness ratio [ICER] = AU$10,786/QALY), and ≥ 75 years group (ICER = AU$36,531/QALY) relative to no updated booster vaccine. The major determinants of the ICER was the vaccine uptake rate. There was inequality in health benefits between the older First Nations versus non-indigenous Australians. The results were robust to simultaneous changes in the parameters' values. The monovalent XBB.1.5 vaccine is cost-effective and still relevant for all adult age groups in Australia. Based on current evidence, the study findings support the promotion of booster vaccination for Australian adults.

The anti-circumsporozoite antibody response to repeated, seasonal booster doses of the malaria vaccine RTS,S/AS01E

The recently deployed RTS,S/AS01E malaria vaccine induces a strong antibody response to the circumsporozoite protein (CSP) on the surface of the Plasmodium falciparum sporozoite which is associated with protection. The anti-CSP antibody titre falls rapidly after primary vaccination, associated with a decline in efficacy, but the antibody titre and the protective response can be partially restored by a booster dose of vaccine, but this response is also transitory. In many malaria- endemic areas of Africa, children are at risk of malaria, including severe malaria, until they are five years of age or older and to sustain protection from malaria for this period by vaccination with RTS,S/AS01E, repeated booster doses of vaccine may be required. However, there is little information about the immune response to repeated booster doses of RTS,S/AS01E. In many malaria-endemic areas of Africa, the burden of malaria is largely restricted to the rainy season and, therefore, a recent trial conducted in Burkina Faso and Mali explored the impact of repeated annual booster doses of RTS,S/AS01E given immediately prior to the malaria transmission season until children reached the age of five years. Anti-CSP antibody titres were measured in sera obtained from a randomly selected subset of children enrolled in this trial collected before and one month after three priming and four annual booster doses of vaccine using the GSK ELISA developed at the University of Ghent and, in a subset of these samples, by a multiplex assay developed at the University of Oxford. Three priming doses of RTS,S/AS01E induced a strong anti-CSP antibody response (GMT 368.9 IU/mL). Subsequent annual, seasonal booster doses induced a strong, but lower, antibody response; the GMT after the fourth booster was 128.5 IU/mL. Children whose antibody response was in the upper and middle terciles post vaccination had a lower incidence of malaria during the following year than children in the lowest tercile. Results obtained with GSK ELISA and the Oxford Multiplex assay were strongly correlated (Pearson’s correlation coefficient, r = 0.94; 95% CI, 0.93–0.95). Although anti-CSP antibody titres declined after repeated booster doses of RTS,S/AS01E a high, although declining, level of efficacy was sustained suggesting that there may have been changes in the characteristics of the anti-CSP antibody following repeated booster doses.Clinical Trials Registration. NCT03143218.

Predictors of moderate, severe, and critical COVID-19 infection in a largely vaccinated kidney transplant recipient cohort during the Omicron era: the importance of timely booster vaccinations and early presentation to care.

Kidney transplant recipients (KTRs) are at risk of coronavirus disease 2019 (COVID-19) complications and mortality. This study examined factors associated with moderate, severe, or critical COVID-19 infection among KTRs during the Omicron-predominant period. This single-center retrospective study included KTRs aged ≥18 years diagnosed with COVID-19 between January 1, 2022, and December 31, 2023. Mild infection was defined as symptomatic illness without lower respiratory tract infection (LRTI); moderate infection as LRTI without hypoxia; severe infection as oxygen saturation <94% on room air; and critical infection as respiratory failure, septic shock, or multiple organ dysfunction. We compared the characteristics of KTRs with asymptomatic or mild COVID-19 versus those with moderate to critical disease. Logistic regression analysis was performed to identify factors associated with moderate to critical illness. Most KTRs (94.4%) had received three or more vaccine doses. Of 603 episodes of COVID-19 infection during the study period, 554 (91.9%) were asymptomatic or mild, while 49 (8.1%) were moderate to critical. Multivariate analysis revealed that older age (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.006-1.069) and longer symptom duration before seeking care (aOR, 1.288; 95% CI, 1.155-1.436) were associated with higher odds of moderate to critical disease. Protective factors included receiving a vaccine booster within the past year (aOR, 0.414; 95% CI, 0.212-0.809) and higher glomerular filtration rate (aOR, 0.971; 95% CI, 0.956-0.986). KTRs should seek care early if infected with COVID-19 and keep their COVID-19 vaccine boosters updated within 1 year of the last dose.

Optimizing rWTC-MBTA Vaccine Formulations, Dosing Regimens, and Cryopreservation Techniques to Enhance Anti-Metastatic Immunotherapy

Metastatic cancer poses significant clinical challenges, necessitating effective immunotherapies with minimal systemic toxicity. Building on prior research demonstrating the rWTC-MBTA vaccine’s ability to inhibit tumor metastasis and growth, this study focuses on its clinical translation by optimizing vaccine composition, dosing regimens, and freezing techniques. The vaccine formula components included three TLR ligands (LTA, Poly I:C, and Resiquimod) and an anti-CD40 antibody, which were tested in melanoma and triple-negative breast cancer (TNBC) models. The formulations were categorized as rWTC-MBT (Mannan-BAM with LTA, Poly I:C, Resiquimod), rWTC-MBL (LTA), rWTC-MBP (Mannan-BAM with Poly I:C), and rWTC-MBR (Resiquimod). In the melanoma models, all the formulations exhibited efficacy that was comparable to that of the full vaccine, while in the “colder” TNBC models, the formulations with multiple TLR ligands or Resiquimod alone performed the best. Vaccine-induced activation of dendritic cell (DC) subsets, including conventional DCs (cDCs), myeloid DCs (mDCs), and plasmacytoid DCs (pDCs), was accompanied by significant CD80+CD86+ population induction, suggesting robust innate immune stimulation. An initial three-dose schedule followed by booster doses (3-1-1-1 or 3-3-3-3) reduced the metastatic burden effectively. Gradual freezing (DMSO-based preservation) maintained vaccine efficacy, underscoring the importance of intact cell structure. These findings highlight the potential of simplified formulations, optimized dosing, and freezing techniques in developing practical, scalable immunotherapies for metastatic cancers.

Financial Incentives for COVID-19 Vaccination

Prior studies found that financial incentives have small, positive direct effects in increasing COVID-19 vaccination rates, but unmeasured social spillovers (ie, changes in outcomes among untreated individuals who are socially exposed to policy beneficiaries) may diminish the overall effect of such policies. To assess the spillover effects of a COVID-19 vaccination financial incentive and assess whether incorporating estimates of spillover meaningfully affects broader evaluations of policy effectiveness. This population-level, address-cluster randomized clinical trial was conducted in November 2021. Participants were all adult (aged ≥18 years) residents of Ravensburg, Germany, who were randomly assigned to the treatment or control group. One resident in each address cluster was randomly selected to be an address-cluster representative. Address-cluster representatives in the treatment group received the treatment letter; all other cohabitants at that same address received the control letter. All individuals in addresses randomly assigned to the control group were mailed a control letter. Intention-to-treat data analysis was conducted from January 2022 to May 2024. Control letters informed recipients about 7 upcoming free COVID-19 vaccination events. Treatment letters were identical to control letters, except they also offered €40 (US $41.46) for getting vaccinated at one of the events. Primary and booster COVID-19 vaccination uptake was observed and recorded on site during the public vaccination events. Primary vaccinations were defined as either the first dose of a 1-dose vaccine or the first or second dose of a 2-doses vaccine. Boosters were defined as any dose after primary vaccination. Three types of commonly used treatment effects were analyzed: direct, spillover, and overall. Among 41 548 Ravensburg residents (mean [SD] age, 49.96 [19.04] years; 51.3% female), 796 (1.9%) were vaccinated at 1 of the 7 public vaccination events. The direct, spillover, and overall effects of receiving a financial incentive on primary vaccinations were all nonsignificant. For booster vaccinations, the direct effect was negative but not statistically significant (-0.32 percentage points [95% CI, -0.77 to 0.14 percentage points]; P = .17), whereas the overall effect (-0.30 percentage points [95% CI, -0.51 to -0.09 percentage points]; P = .006) was significantly negative. The spillover effect was significantly negative (-0.29 percentage points [95% CI, -0.53 to -0.06 percentage points]; P = .01), but only for the first vaccination events. This trial found null direct effects on COVID-19 vaccination uptake and negative effects on booster uptake among individuals who did not receive but were indirectly exposed to the financial incentives. The timing of this spillover suggests that cohabitants of financial incentive recipients postponed booster vaccination, thereby undermining the potential effectiveness of this policy. ISRCTN identifier: ISRCTN59503725.

Neutralizing antibody responses to three XBB protein vaccines in older adults

The ongoing COVID-19 pandemic has underscored the importance of strong immune defenses against emerging SARS-CoV-2 variants. While COVID-19 vaccines containing XBB subvariants have proven effective in neutralizing new SARS-CoV-2 variants, a gap remains in knowledge regarding neutralizing antibody responses in older adults aged >65 years against these newly emerged variants. This study was therefore undertaken to investigate and compare neutralizing antibody responses to three XBB-containing protein-based vaccines (trivalent XBB.1.5 vaccine, bivalent Omicron XBB vaccine, and tetravalent XBB.1 vaccine) head-to-head in 90 individuals aged >65 years. The results showed that all three XBB-containing vaccines substantially enhanced the neutralizing antibody response, with 100% of vaccinees having detectable antibody titers against ancestral D614G and variants BA.5, XBB.1.5, JN.1, KP.2, and KP.3 after booster immunization. Subsequent analysis indicated that the trivalent XBB.1.5 and tetravalent XBB.1 vaccines elicited higher levels of neutralizing antibodies compared to the bivalent Omicron XBB vaccine. The KP.2 and KP.3 variants displayed antibody resistance comparable to the JN.1 variant. Older adults produce similar neutralizing antibody responses to the vaccines regardless of their underlying medical conditions. These findings indicate that booster vaccination with XBB-containing vaccines can effectively elicit strong neutralizing responses against a number of SARS-CoV-2 variants in older adults over 65 years, which will help guide vaccine strategies in this elderly population.

Growth hormone replacement therapy enhances humoral response to COVID-19 mRNA vaccination in patients with adult-onset growth hormone deficiency.

Given the established link between GH/insulin-like growth factor 1 (IGF-1) deficiency and severe COVID-19 outcomes, this research seeks to determine whether GH therapy can enhance vaccine efficacy in patients with adult-onset growth hormone deficiency (aGHD). We conducted an observational retrospective study involving two groups: a cohort of 10 patients (8 females, 2 males) with obesity and aGHD who initiated recombinant GH replacement therapy at a standard dose of 0.1mg/day six months to one year before their first vaccine dose, and a matched control group of 7 patients (5 females, 2 males) with aGHD who had not started GH treatment. Both groups were matched for age, gender, and body mass index (BMI) to ensure comparability. Blood samples were collected 3 to 6months after the third booster dose of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech) and analyzed for anti-SARS-CoV-2 antibodies using a commercially available assay. The GH-treated group exhibited a significantly greater humoral response compared to the untreated group, with a mean antibody titer of 19,122.1 ± 7,736.84 U/mL versus 9,539.14 ± 5,408.90 U/mL in the control group (p = 0.01). Multivariate regression analysis revealed that GH replacement therapy was the only statistically significant predictor of vaccine response, while factors such as male sex, age, and visceral adipose tissue showed negative correlations that did not reach significance. Our findings suggest that GH replacement therapy may enhance the immune response to COVID-19 vaccination in patients with aGHD, potentially improving their overall metabolic health and immune function.

Post-COVID symptoms after SARS-CoV-2 omicron infection and the effect of booster vaccination: A population-based cohort study.

The impact of vaccination on the type and risk of specific post-COVID symptoms after Omicron infection is not clear. We aimed to investigate the excess risk and patterns of 22 symptoms 3-5months after Omicron infection, comparing uninfected and infected subjects with and without recent booster vaccination. We conducted a population-based prospective study based on four questionnaire-based cohorts linked to national health registries. Our study includes female and male participants aged 11-80years from The Norwegian Mother, Father, and Child Cohort Study, The Norwegian Influenza Pregnancy Cohort, The Senior Cohort, and The Young Adult Cohort. All participants registered presence of 22 COVID-related symptoms irrespective of infection and vaccination status. The study sample includes more than 31,000 uninfected and 26,000 Omicron infected subjects. Among infected subjects, 12% were vaccinated with two doses >130days before the primary infection (median 154days) but had not received a third dose, while 76% had received a third (booster) dose (median 40days before infection). Among those with two doses only, the excess risk for new symptoms after infection (vs. no infection) were up to 15% for women and 9% for men. Among infected subjects with recent booster dose, the corresponding excess risks were 7% among women and up to 5% among men. The largest risk differences after recent booster vaccination were seen for poor memory, brain fog, and fatigue. Post-COVID symptoms were more often detected among young and middle-aged adults than among adolescents and older age groups. Recent booster vaccination before infection substantially reduced both neurocognitive and cardiorespiratory symptoms occurring at least 3months after Omicron infection.

Evaluation of anti-Pertussis antibody levels in Iranian infants and children: Is it time to include booster acellular Pertussis Vaccines in the immunization schedule?

The prevalence of anti-pertussis antibodies among infants and children in Iran has not been thoroughly investigated. Given that recommendations for booster vaccines are based on national disease epidemiology, we aimed to evaluate the seroprevalence of pertussis antibodies among infants and children in an Iranian referral hospital. A total of 1012 infants and children were included in the study. Serum samples were stored at -20°C until analysis. Demographic characteristics of patients, including age, sex, trivalent diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccination status, and time since DTwP vaccination were collected. Anti-pertussis IgG antibodies were measured using a commercial ELISA kit. In this cross-sectional study, the median age of the participants was 35months (IQR:9-72months). In infants ≤2months, only 15% had positive anti-pertussis antibodies. This increased to 28% in the 3 to 4months group and 55% in the 5 to 6months group. The highest positivity rates (63% and 66%) were seen in the 7 to 18months and 19 to 36months age groups, respectively. Positivity declined to 45% in the 37 to 72months group, and 47% in those over 72months. A significant relationship was found between the time elapsed since vaccination and anti-pertussis IgG levels (p=0.005). Our study highlights a concerning prevalence of low anti-pertussis, especially among infants aged ≤2months, where the majority displayed negative results. This situation underscores the vulnerability of newborns to pertussis due to insufficient immunity and emphasizes the urgent need for effective maternal vaccination strategies. Additionally, we observed a decline in anti-pertussis IgG levels after 36months, raising concerns about waning immunity in older children. Continued research is crucial to evaluate the long-term efficacy of booster vaccines and to develop optimal vaccination strategies to protect infants and children from pertussis.

Immunogenicity of yellow fever vaccine co-administered with 13-valent pneumococcal conjugate vaccine in rural Gambia: A cluster-randomised trial.

Because booster doses of pneumococcal conjugate vaccine (PCV) may be given at a similar time to yellow fever vaccine (YF), it is important to assess the immune response to YF when co-administered with PCV. This has been investigated during a reduced-dose PCV trial in The Gambia. In this phase 4, parallel-group, cluster-randomized trial, healthy infants aged 0-10weeks were randomly allocated to receive either a two-dose schedule of PCV13 with a booster dose co-administered with YF vaccine at age 9months (1+1 co-administration) or YF vaccine administered separately at age 10months (1+1 separate) or the standard three early doses of PCV13 with YF vaccine at age 9months (3+0 separate). Blood samples were collected 28-35days post-vaccination and YF neutralizing antibody (NA) titres were measured. Proportions with seroprotective YF NA titres≥1:8 were calculated with 95% confidence intervals (CI). Non-inferiority was demonstrated if the lower limit of the CI for the difference in proportions between the co-administration and separate groups was greater than-10%. Forty-eight, 66, and 98 participants enrolled in 3+0 separate, 1+1 co-administration, and 1+1 separate groups respectively had NA results. Per protocol analysis of the 3+0 separate, 1+1 co-administration, 1+1 separate, and the combined 1+1 separate and 3+0 separate groups found that 81%, 85%, 92%, and 88% of participants respectively had YF NA titres ≥1:8. Results were similar with analysis by intention-to-treat. The difference in proportions comparing 1+1 co-administration and 1+1 separate groups was -7% (95% CI, -18% to 3%). The difference between 1+1 co-administration and 3+0 separate groups was 4% (95% CI, -10% to 15%). There was no statistical difference in the YF seroresponse when the YF vaccine was co-administered with PCV or administered separately. No evidence was found of the non-inferiority of the seroresponse to YF vaccine when co-administered with PCV13. The levels of YF NA attaining seroprotection (NT ≥1:8) were high in all groups. PCV13 co-administered with YF vaccine at 9months does not affect seroresponse to YF vaccine. http://www.isrctn.org/ - ISRCTN72821613.

Purpura Annularis Telangiectodes of Majocchi Following a Booster Dose of the Pfizer-BioNTech COVID-19 Vaccine: Coincidence or Correlation?

Purpura Annularis Telangiectodes of Majocchi Following a Booster Dose of the Pfizer-BioNTech COVID-19 Vaccine: Coincidence or Correlation?

Impact of vaccination against SARS-CoV-2 on mortality risk, ICU admission rate, and hospitalization length in hospitalized COVID-19 patients: a cross-sectional study

BackgroundVaccination against SARS-CoV-2 has been crucial in impeding virus spread and preventing fatal complications. Despite growing evidence of vaccine efficacy, data on its impact on hospitalized patients remain limited. We aimed to estimate the risk of mortality, ICU admission, and hospitalization length among hospitalized COVID-19 patients based on vaccination status.MethodsIn this single-center cross-sectional study, we included patients above 16 years old hospitalized due to COVID-19. Patients were categorized as unvaccinated, partially vaccinated (single dose), or fully vaccinated (at least one booster dose). We performed logistic and linear regression analyses, including both bivariable and multivariable models, to evaluate the association between vaccination status, demographic characteristics, and study outcomes.ResultsOf 299 participants, 21.7%, 15.7%, and 62.5% were unvaccinated, partially vaccinated, and fully vaccinated, respectively. Full vaccination was associated with significantly reduced mortality risk (OR: 0.235, 95%CI: 0.103–0.538) and lower ICU admission rates (OR: 0.252, 95%CI: 0.131–0.484). Vaccinated patients had shorter hospital stays (fully vaccinated: 6.38 ± 1.65 days; unvaccinated: 9.22 ± 2.84 days, p < 0.001). Older age independently predicted higher mortality (OR: 1.062, 95%CI: 1.030–1.095), ICU admission (OR: 1.047, 95%CI: 1.027–1.068), and longer hospital stays (estimate: 0.027, 95%CI: 0.012–0.043). Multiple comorbidities were associated with higher mortality and longer hospitalization (OR: 1.794, 95%CI: 1.244–2.587; estimate: 0.395, 95%CI: 0.142–0.648).ConclusionFull vaccination against SARS-CoV-2 is associated with significantly improved clinical outcomes in hospitalized COVID-19 patients, including reduced mortality, lower ICU admission rates, and shorter hospital stays.

P-1988. COVID-19 vaccine induced antibodies in human milk: exploring form and function

Abstract Background Following SARS-CoV-2 vaccination/infection of pregnant/lactating women, human milk contains SARS-CoV-2 antibodies (Ab). Limited data exists on whether those Ab induce protection for infants against COVID-19. Among 45 lactating women who received primary and booster SARS-CoV-2 vaccines from 2021 to 2022, we previously showed that anti-receptor binding domain (RBD) IgG and IgA significantly increased in serum and milk following booster SARS-CoV-2 vaccine but did not differ by maternal nucleoprotein (NP) status. In this exploratory analysis, we aimed to further characterize the Ab present in human milk following maternal booster SARS-CoV-2 vaccination. SARS-CoV-2 Neutralization Antibodies in Human Milk by Maternal Nucleoprotein Status before and after SARS-CoV-2 Booster Vaccine. Neutralization titers in human milk significantly increased among women with hybrid immunity (NP+) after booster vaccine (P=0.04) but not for women with vaccine only immunity (NP-). Methods Using a subset of paired longitudinal milk and blood samples from a cohort of 45 lactating women who received primary and booster SARS-CoV-2 vaccines from 2021 to 2022, we characterized neutralizing Ab, RBD IgG subclasses (IgG1-IgG4), and Ab-dependent complement activation (ADCA). Antibody-Dependent Complement Activation (ADCA) using Human Milk from Lactating Women before and after SARS-CoV-2 Booster Vaccine. Two women with hybrid immunity (NP+) had significantly positive ADCA after SARS-CoV-2 booster vaccine, human milk from all others resulted in low or no activation of complement. Results For 7 NP+ (hybrid immune) and 7 NP- (vaccine immune) women, SARS-CoV-2 neutralization titers increased in serum and milk after booster vaccine among NP+ women (p=0.04) but not for NP- women (Fig1). After booster vaccine, ADCA was positive but variable in maternal serum and milk with only 2/12 (16%) women demonstrating high-levels of ADCA in human milk (Fig2). These same two women demonstrated different IgG subclass profiles in milk after booster vaccine with moderate to high levels of IgG1 and IgG3, and low levels of IgG4 (Fig3). This was inverse for all other women who demonstrated moderate to low levels of IgG1 and high titers of IgG4 in human milk. Notably, both women with high ADCA response were NP+ and vaccinated with primary SARS-CoV-2 vaccine more than 4 months post-partum, while all others received primary SARS-CoV-2 vaccine while pregnant or less than a month post-partum. IgG Subclasses in Human Milk before and after SARS-CoV-2 booster vaccine by Complement Activation Status Human milk with high complement activation demonstrated higher levels of IgG1 and IgG3 after booster vaccine compared to women with low complement activation. Conclusion The different Ab profile may indicate a tolerizing response that could be related to pregnancy at time of initial antigen exposure or from repeat SARS-CoV-2 vaccination and warrants future investigation (additional samples are under analysis). Nonetheless, human milk demonstrates robust binding and neutralizing Ab following SARS-CoV-2 vaccination, offering other potential mechanisms for protection of infants against COVID-19 infection. Disclosures Anne-Marie Rick, MD, MPH, PhD, Pfizer: Advisor/Consultant

P-98. The Platform Trial In COVID-19 priming and BOOsting (PICOBOO): the immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in BNT162b2 primed individuals aged 18-&amp;lt; 50 and 50-&amp;lt; 70 years old

Abstract Background PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we report data for second boosters among individuals aged 18-&amp;lt; 50 and 50-&amp;lt; 70 years old primed with BNT162b2 (18-&amp;lt; 50y-BNT162b2 and 50-&amp;lt; 70y-BNT162b2, respectively) until Day (D) 84. CONSORT diagram for participants recruited to the 18-&amp;lt;50y-BNT162b2 (A) and 50-&amp;lt;70y-BNT162b2 (B) strata for second booster vaccines. Participants were excluded from subsequent analyses if they were infected with COVID-19 (C19 Infection) or had withdrawn. Participants that missed visits (Missed) were eligible to be included in subsequent analyses. CONSORT diagram for participants recruited to the 18-&amp;lt;50y-BNT162b2 (A) and 50-&amp;lt;70y-BNT162b2 (B) strata for second booster vaccines. Participants were excluded from subsequent analyses if they were infected with COVID-19 (C19 Infection) or had withdrawn. Participants that missed visits (Missed) were eligible to be included in subsequent analyses. Methods Immunocompetent adults who received any licensed first booster at least three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The log10 concentration of anti-spike IgG was summarised as the geometric mean concentration (GMC). Reactogenicity and safety outcomes were captured. Additional analyses were performed on a subset. ACTRN12622000238774. Baseline characteristics for study participants recruited to the 18-&amp;lt;50y-BNT162b2 and 50-&amp;lt;70y BNT162b2 strata for second booster vaccines summarised according to study arm. Baseline characteristics for study participants recruited to the 18-&amp;lt;50y-BNT162b2 and 50-&amp;lt;70y BNT162b2 strata for second booster vaccines summarised according to study arm. Results Between 29 Mar 2022 and 7 Jul 2023, 743 participants were recruited to the platform with D28 samples; 120 belonged to the 18-&amp;lt; 50y-BNT162b2 and 103 belonged to the 50-&amp;lt; 70y-BNT162b2 strata. At D28, the GMCs (95% credible intervals) were 40 338 (32 978, 47 813), 48 117 (39 603, 57 826) and 24 220 (19 586, 29453) U/L in the 18-&amp;lt; 50y-BNT162b2 stratum following BNT162b2, mRNA-1273 and NVX-CoV2372, respectively. Corresponding values in the 50-&amp;lt; 70y-BNT162b2 stratum were 29 344 (23 763, 35 163), 36 026 (29 042, 43456) and 16 040 (12 923, 19 510) U/L. By D84, GMCs fell to 24 643 (17 779, 31 708), 33 236 (24 078, 42, 798) and 20 898 (14 978, 27 596) in the 18-&amp;lt; 50y-BNT162b2 stratum, respectively. D84 GMCs in the 50-&amp;lt; 70y-BNT162b2 stratum were 19 782 (14 157, 25 771), 24 817 (17 740, 32 024) and 15 310 (11 0349, 19 784) U/mL. At D28, neutralisation against wild-type virus was 172, 211 and 74 IU/mL following BNT162b2, mRNA-1273 and NVX-CoV2372. By D84, this fell to 95, 157 and 72 IU/mL. Limited neutralisation against BA.5 and XBB1.5 was found following all vaccines. Severe reactogenicity events were low (&amp;lt; 5%). Additional data will be available at the time of presentation. Posterior distributions of the anti-spike IgG adjusted GMC against Ancestral SARS-CoV-2 at D7, D28 and D84 for each study arm in participants recruited to the 18-&amp;lt;50y-BNT162b2 and 50-&amp;lt;70y-BNT162b2 strata for second booster vaccines without COVID-19 infection after randomisation and before D28 (D7 for D7 distributions). Posterior distributions of the anti-spike IgG adjusted GMC against Ancestral SARS-CoV-2 at D7, D28 and D84 for each study arm in participants recruited to the 18-&amp;lt;50y-BNT162b2 and 50-&amp;lt;70y-BNT162b2 strata for second booster vaccines without COVID-19 infection after randomisation and before D28 (D7 for D7 distributions). Conclusion Each COVID-19 vaccine elicited boosted antibody responses to wild-type virus among BNT162b2-primed adults. GMCs and neutralisation titres were higher in the younger cohort compared to older adults. Minimal neutralisation was observed against Omicron subvariants, highlighting the need for boosting with vaccines with greater specificity for Omicron subvariants. Posterior distributions of the adjusted geometric mean NF50 of Ancestral SARS-CoV-2 at D28 and D84 for each study arm in participants recruited to the 18-&amp;lt;50y-BNT162b2 and 50-&amp;lt;70y-BNT162b2 strata for second booster vaccines without COVID-19 infection after randomisation and before D28 in the immunological subset. Posterior distributions of the adjusted geometric mean NF50 of Ancestral SARS-CoV-2 at D28 and D84 for each study arm in participants recruited to the 18-&amp;lt;50y-BNT162b2 and 50-&amp;lt;70y-BNT162b2 strata for second booster vaccines without COVID-19 infection after randomisation and before D28 in the immunological subset. Disclosures Magdalena Plebanski, PhD, AstraZeneca: Grant/Research Support Helen Marshall, MD, ILiAD biotechnologies: Grant/Research Support Saul N. Faust, FRCPCH PhD, AstraZeneca: Grant/Research Support|BioNTech: Grant/Research Support|GSK: Grant/Research Support|Iliad Biotechnologies: Grant/Research Support|J&amp;J: Grant/Research Support|J&amp;J: Advisor, no personal payments (all honoraria paid to employing hospital)|Moderna: Grant/Research Support|Novavax: Advisor, no personal payments (all honoraria paid to employing hospital)|Pfizer: Advisor, no personal payments (all honoraria paid to employing hospital)|Sanofi: Grant/Research Support|Sanofi: Advisor, no personal payments (all honoraria paid to employing hospital)|Valneva: Grant/Research Support Peter Richmond, MBBS, ILiAD biotechnologies: Grant/Research Support

86. The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): the immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster (fourth dose) in AZD1222 primed individuals aged 50-&amp;lt; 70 years old

Abstract Background PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. Here, we report data for second boosters among individuals aged 50-&amp;lt; 70 years old primed with AZD1222 (50-&amp;lt; 70y-AZD1222) until Day (D) 84. CONSORT diagram CONSORT diagram for participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines. Participants were excluded from subsequent analyses if they were infected with COVID-19 (C19 Infection) or had withdrawn. Participants that missed visits (Missed) were eligible to be included in subsequent analyses. Methods Immunocompetent adults who received any licensed first booster at least three months prior were eligible. Participants were randomly allocated to BNT162b2, mRNA-1273 or NVX-CoV2373 1:1:1. The log10 concentration of anti-spike IgG was summarised as the geometric mean concentration (GMC). Reactogenicity and safety outcomes were captured. Additional analyses were performed on a subset. ACTRN12622000238774. Baseline characteristics for study participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines summarised according to study arm. Baseline characteristics for study participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines summarised according to study arm. Results Between 29 Mar 2022 and 2 Aug 2023, 743 participants were recruited and had D28 samples; 155 belonged to the 50-&amp;lt; 70y-AZD1222 stratum. At D28, the mean adjusted GMCs (95% credible intervals) were 20 690 (17 555, 23 883), 23 867 (20 144, 27 604) and 8 654 (7 267, 9 962) U/mL following boosting with BNT162b2, mRNA-1273 and NVX-CoV2372, respectively. By D84, adjusted GMCs fell to 10 976 (8 826, 13 196), 15 779 (12 512, 19 070) and 6 559 (5 220, 7 937) U/mL in each group, respectively. At D28, mean adjusted neutralisation against Ancestral virus was 159, 213 and 75 IU/mL and 100, 156 and 72 IU/mL by D84 in each group. Limited neutralisation against Omicron subvariants BA.5 and XBB.1.5 was found following boosting with all vaccines. Severe reactogenicity events were few (&amp;lt; 4%). Further data will be available at the time of presentation. Posterior distributions of the anti-spike IgG adjusted GMC against Ancestral SARS-CoV-2 at D7, D28 and D84 for each study arm in participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines without COVID-19 infection after randomisation and before D28 (D7 for D7 distributions). Posterior distributions of the anti-spike IgG adjusted GMC against Ancestral SARS-CoV-2 at D7, D28 and D84 for each study arm in participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines without COVID-19 infection after randomisation and before D28 (D7 for D7 distributions). Conclusion These are the first randomised clinical trial data globally of the immunogenicity, reactogenicity and safety of second booster (fourth doses) of mRNA and protein subunit COVID-19 vaccines in adults previously primed with two doses of AZD1222. BNT162b2, mRNA-1273 and NVX-CoV2372 were well tolerated and boosted humoral immune responses. Higher binding and neutralising antibodies against Ancestral SARS-CoV-2 were observed following boosting with mRNA vaccines (BNT162b2 and mRNA-1273) compared to NVX-CoV2372 at all time points. Lower neutralising antibody responses were observed against Omicron subvariants BA.5 and XBB.1.5 following all vaccines until Day 84 highlighting the need for boosting with vaccines with greater specificity for Omicron subvariants. Posterior distributions of the adjusted geometric mean NF50 of Ancestral SARS-CoV-2 at D28 and D84 for each study arm in study participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines without COVID-19 infection after randomisation and before D28 in the immunological subset. Posterior distributions of the adjusted geometric mean NF50 of Ancestral SARS-CoV-2 at D28 and D84 for each study arm in study participants recruited to the 50-&amp;lt;70y-AZD1222 stratum for second booster vaccines without COVID-19 infection after randomisation and before D28 in the immunological subset. Disclosures Magdalena Plebanski, PhD, AstraZeneca: Grant/Research Support Helen Marshall, MD, ILiAD biotechnologies: Grant/Research Support Saul N. Faust, FRCPCH PhD, AstraZeneca: Grant/Research Support|BioNTech: Grant/Research Support|GSK: Grant/Research Support|Iliad Biotechnologies: Grant/Research Support|J&amp;J: Grant/Research Support|J&amp;J: Advisor, no personal payments (all honoraria paid to employing hospital)|Moderna: Grant/Research Support|Novavax: Advisor, no personal payments (all honoraria paid to employing hospital)|Pfizer: Advisor, no personal payments (all honoraria paid to employing hospital)|Sanofi: Grant/Research Support|Sanofi: Advisor, no personal payments (all honoraria paid to employing hospital)|Valneva: Grant/Research Support Peter Richmond, MBBS, ILiAD biotechnologies: Grant/Research Support

P-2057. Immunogenicity of COVID-19 Booster Vaccines in Mexico and Mongolia

Abstract Background InVITE (NCT# 05096091) is a 7-country observational study assessing immune responses to COVID-19 vaccines offered from national vaccination programs. This analysis focuses on the response 2 months after receipt of a booster vaccine (third dose) among participants from Mexico and Mongolia. Vaccines assessed were mRNA (Comirnaty, Pfizer (BioNTech), non-replicating viral vector (Vaxzevria, Oxford/AstraZeneca; Sputnik-V, Gam-COVID-Vac), or inactivated virus vaccines (CoronaVac, SinoVac and Covilo, Sinopharm). Methods Blood samples were taken at baseline (Visit 1) and 2 months after receipt of booster (Visit 2). Information on primary vaccine regimens (receipt of first 2 COVID-19 vaccine doses) was collected. Quanterix SARS-CoV-2 Spike IgG assay measured anti-Spike (S) antibody levels. BioRad Platelia SARS-CoV-2 assessed anti-Nucleocapsid pan Ig (anti-N) antibody levels. Multivariate regression models were used to compare booster vaccines and regimens (primary+booster) based on log10 anti-S levels. CoronaVac and Covilo were excluded from some analyses due to small numbers (≤10 participants). Violin plot with estimates and 95% confidence intervals (CI) of anti-S levels at Visit 1 and Visit 2. Groups with &amp;gt;10 participants were included. Results We report on 698 participants with Visit 1 and Visit 2 anti-S levels measured. 59.5% were women, 46.3% were 40-59 and 24.4% were ≥60 years old. 33.7% reported hypertension/diabetes and 22.2% had body mass index &amp;gt;30. 65.6% and 70.8% were positive for anti-N antibodies, at Visit 1 and 2, respectively. Anti-S levels at Visits 1 and 2 are shown in Figure 1. After adjusting for country, the booster with Comirnaty produced higher anti-S levels compared to Vaxzevria and Sputnik V, and Sputnik V produced relatively higher levels than Vaxzevria (Figure 2). When comparing combinations of primary and booster vaccines, Comirnaty + Comirnaty had the highest anti-S levels (Figure 3). Difference between log10 anti-S levels at Visits 1 and 2 with 95% CI for comparison of booster vaccines, adjusted for country. Conclusion Immune response to booster COVID-19 immunization differed by vaccine with the highest response seen when Comirnaty was included in a regimen. These data, including vaccines and geographic locations rarely reported in other studies, enrich understanding of immunogenicity to different combinations of vaccines used as primary and booster doses. Figure 3 Difference between vaccine combinations (primary vaccine + booster vaccine) log 10 anti-S levels with 95% CI to compare combinations. Rows without a line indicate 'no data' for those combinations. Disclosures Juan Pablo Ramírez-Hinojosa, MD, Abott: Honoraria|Jansen: Honoraria|Silanes: Honoraria Irini Sereti, M.D., NeoImmunotech: Collaboration

P-599. 6-Valent, OspA-Based VLA15 Lyme Disease Vaccine Candidate Against Lyme Borreliosis in a Healthy Pediatric and Adult Study Population: A Phase 2 Study Update

Abstract Background Lyme borreliosis (LB) is the most common tick-borne disease in the US, with approximately 476,000 cases diagnosed and treated annually and nearly 90 million individuals living in high incidence jurisdictions. Vector-focused prevention measures have varying levels of effectiveness due to low utilization, poor adherence, or high cost. A safe and efficacious vaccine to prevent LB is warranted. We provide an update on the Pfizer-Valneva VLA15 vaccine clinical development program, specifically the safety and immunogenicity booster data of the phase 2 trial (NCT04801420). Methods A randomized, observer-blinded, multi-centre Phase 2 study investigated the safety and immunogenicity of VLA15 in adult and pediatric study populations. A total of 625 participants aged 5-65 years were enrolled in three age groups (5-11 years, 12-17 years, and 18-65 years) and randomized 1:1:1 to receive VLA15 180 mcg with alum in a three-dose (Month 0-2-6) or a two-dose schedule (Month 0-6), or three injections of placebo (Month 0-2-6) followed by booster doses at Month 18 and Month 30. Safety and immunogenicity data up to one month after completion of the primary vaccination series and yearly booster doses are presented. Results Up to Month 19, VLA15 was safe and well tolerated in all age groups after all doses. Most adverse reactions were mild or moderate in severity. No related SAEs or other safety concerns were reported. The VLA15 booster dose induced a robust, anamnestic immune response against all six OspA vaccine serotypes in all age groups. Immune responses in children were higher than in adults across both schedules. Conclusion The Month 18 VLA15-221 booster dose was safe and immunogenic in both adults and children. The Month 30 booster data is under analysis. The ongoing blinded Phase 3 trials in Europe and North America will provide additional data which may support use of this vaccine as the primary preventative measure to protect against LB. Disclosures Marc D. Messier, PhD, SOBI: Advisor/Consultant|Valneva: employee|Valneva: Ownership Interest Laura Wagner, M.Sc., Valneva: employee Romana Hochreiter, PhD, Valneva Austria GmbH: WO2021/207615 A1|Valneva Austria GmbH: Employee, owner of stock options Erik Lamberth, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Julian Larcher-Senn, PhD, Valneva: Advisor/Consultant Raphael Simon, PhD, Pfizer: Stocks/Bonds (Private Company) James groark, MD, Pfizer: Stocks/Bonds (Public Company) James H. Stark, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)