Two-dose Vaccine Regimen Research Articles

Inactivated vaccine dosage and serum IgG levels correlate with persistent COVID-19 infections in hematologic malignancy patients during the Omicron Surge in China

PurposeThe essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant.MethodsAdults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed.ResultsIn the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001).ConclusionsIn conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels.

A cost benefit analysis of varicella vaccination in South Korea

BackgroundThe introduction of varicella vaccination has significantly reduced the burden of chickenpox in many countries, but outbreaks still occur in populations with high vaccination coverage. To address this, some countries, including the United States, Germany, and Japan, have adopted a two-dose varicella vaccination recommendation. Economic evaluations are crucial for assessing vaccine recommendations; however, there are limited studies exist in Asian countries. Thus, our study aimed to evaluate the cost-benefit of one-dose and two-dose varicella vaccination programs compared to no vaccination in South Korea, incorporating updated data on disease burden and costs. MethodsWe utilized data from South Korea’s health databases to estimate varicella burden and vaccination records. Decision tree analysis was employed to compare costs and benefits of vaccination strategies over a ten-year period for the 2012 birth cohort. Sensitivity analyses were conducted to assess the impact of various variables. ResultsBoth one-dose and two-dose vaccination programs showed cost-benefit compared to no vaccination, with substantial societal cost savings. The one-dose program yielded a benefit-cost ratio (BCR) of1.43, while the two-dose program had a direct BCR of1.28. Sensitivity analyses confirmed the robustness of these findings. ConclusionOur study demonstrates the economic benefits of varicella vaccination in South Korea, aligning with findings from other countries. While the second dose did not show additional cost savings compared to the one-dose program, other factors like disease severity and transmission dynamics should be considered. Implementing either a one-dose or two-dose varicella vaccination regimen in South Korea could lead to cost reductions and improved cost-effectiveness compared to no vaccination, emphasizing the importance of vaccination programs in reducing disease burden and enhancing public health outcomes.

Effectiveness of two-dose vs. one-dose varicella vaccine in children in Shanghai, China: a prospective cohort study.

Varicella, a highly contagious viral disease caused by the varicella-zoster virus (VZV), affects millions globally, with a higher prevalence among children. After the initial infection, VZV lies dormant in sensory ganglia and has the potential to reactivate much later, causing herpes zoster (HZ). Vaccination is one of the most effective methods to prevent varicella, and the two-dose varicella vaccine (VarV) regimen is widely used around the world. In China, the VarV has been included in the national immunization programme with a recommended single-dose regimen. This study aimed to compare the effectiveness of the two-dose vs. one-dose VarV regimen in children in Shanghai, China. A prospective cohort study was conducted in Shanghai, China, from September 2018 to December 2022. The study enrolled children aged 3-18 years who had received either the one-dose, two-dose, or 0-dose VarV regimen. Vaccination history, varicella infection status, and relevant variables, including demographic information (name, date of birth and sex) and medical history (clinical features of varicella and illness duration) were collected through medical record review and parental interviews. A total of 3,838 children were included in the study, with 407 in the 0-dose regimen group, 2,107 in the one-dose regimen group and 1,324 in the two-dose regimen group. The corresponding incidence density in these groups was 0.13, 0.05 and 0.03 cases per 1,000 person-days, respectively. The adjusted vaccine effectiveness (VE) was 81.7% (95%CI: 59.3-91.8%) for the two-dose regimen and 60.3% (95%CI: 29.3-77.7%) for the one-dose regimen, compared to the 0-dose regimen. The two-dose VarV regimen showed a protective effectiveness of 47.6% (95%CI: 2.5-71.9%) compared to the one-dose VarV regimen. This study provides evidence supporting the greater effectiveness of the two-dose VarV regimen in preventing varicella infection compared to the one-dose regimen.

Cell immunity to SARS-CoV-2 after natural infection and/or different vaccination regimens.

The aim of the study was to evaluate the humoral and cellular immunity after SARS-CoV-2 infection and/or vaccination according to the type of vaccine, number of doses and combination of vaccines. Volunteer subjects were sampled between September 2021 and July 2022 in Hospital Clínico San Carlos, Madrid (Spain). Participants had different immunological status against SARS-CoV-2: vaccinated and unvaccinated, with or without previous COVID-19 infection, including healthy and immunocompromised individuals. Determination of IgG against the spike protein S1 subunit receptor-binding domain (RBD) was performed by chemiluminescence microparticle immunoassay (CMIA) using the Architect i10000sr platform (Abbott). The SARS-CoV-2-specific T-cell responses were assessed by quantification of interferon gamma release using QuantiFERON SARS-CoV-2 assay (Qiagen). A total of 181 samples were collected, 170 were from vaccinated individuals and 11 from unvaccinated. Among the participants, 41 were aware of having previously been infected by SARS-CoV-2. Vaccinated people received one or two doses of the following vaccines against SARS-CoV-2: ChAdOx1-S (University of Oxford-AstraZeneca) (AZ) and/orBNT162b2 (Pfizer-BioNTech)(PZ). Subjects immunized with a third-booster dose received PZ or mRNA-1273 (Moderna-NIAID)(MD) vaccines. All vaccinees developed a positive humoral response (>7.1 BAU/ml), but the cellular response varied depending on the vaccination regimen. Only AZ/PZ combination and 3 doses of vaccination elicited a positive cellular response (median concentration of IFN- γ > 0.3 IU/ml). Regarding a two-dose vaccination regimen, AZ/PZ combination induced the highest humoral and cellular immunity. A booster with mRNA vaccine resulted in increases in median levels of IgG-Spike antibodies and IFN-γ as compared to those of two-dose of any vaccine. Humoral and cellular immunity levels were significantly higher in participants with previous infection compared to those without infection. Heterologous vaccination (AZ/PZ) elicited the strongest immunity among the two-dose vaccination regimens. The immunity offered by the third-booster dose of SARS-CoV-2 vaccine depends not only on the type of vaccine administered but also on previous doses and prior infection. Previous exposure to SARS-CoV-2 antigens by infection strongly affect immunity of vaccinated individuals.

Effectiveness of the BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years: A systematic review and meta-analysis.

A rapid systematic review, based on Cochrane rapid review methodology was conducted to assess the effectiveness of two 10μg doses of BNT162b2 vaccine in preventing morbidity and mortality associated with COVID-19 in children aged 5 to 11 years. We searched the Cochrane Library COVID-19 study register, the COVID-NMA living review database and the McMaster University Living Evidence Synthesis for pre-appraised trials and observational studies up to 7 December 2022. Records were screened independently in duplicate. Where appraisal was not available, these were done in duplicate. Meta-analysis was conducted using RevMan 5.3 presenting risk ratios/odds ratios/inverse vaccine efficacy with 95% confidence intervals (CI). GRADE for assessing the overall certainty of the evidence was done in Gradepro. We screened 403 records and assessed 52 full-text articles for eligibility. One randomised controlled trial (RCT) and 24 observational studies were included. The RCT reported that BNT162b2 was likely safe and 91% efficacious, RR 0.09 (95% CI 0.03 to 0.32) against incident COVID-19 infection (moderate certainty evidence). In absolute terms, this is 19 fewer cases per 1,000 vaccines delivered (ranging from 15 to 21 fewer cases). Observational studies reported vaccine effectiveness (VE) against incident COVID-19 infection of 65% (OR 0.35, 95% CI 0.26 to 0.47) and 76% against hospitalisation (OR 0.24, 95% CI 0.13 to 0.42) (moderate certainty evidence). The absolute effect is 167 fewer cases per 1,000 vaccines given (ranging from 130 fewer to 196 fewer cases) and 4 fewer hospitalisations per 10,000 children (from 3 fewer to 5 fewer hospitalisations). Adverse events following vaccination with BNT162b2 were mild or moderate and transient. The evidence demonstrated a reduction in incident COVID-19 cases and small absolute reduction in hospitalisation if a two-dose BNT162b2 vaccine regimen is offered to children aged 5 to 11 years, compared to placebo. PROSPERO registration: CRD42021286710.

Prediction of long-term humoral response induced by the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine against Ebola

The persistence of the long-term immune response induced by the heterologous Ad26.ZEBOV, MVA-BN-Filo two-dose vaccination regimen against Ebola has been investigated in several clinical trials. Longitudinal data on IgG-binding antibody concentrations were analyzed from 487 participants enrolled in six Phase I and Phase II clinical trials conducted by the EBOVAC1 and EBOVAC2 consortia. A model based on ordinary differential equations describing the dynamics of antibodies and short- and long-lived antibody-secreting cells (ASCs) was used to model the humoral response from 7 days after the second vaccination to a follow-up period of 2 years. Using a population-based approach, we first assessed the robustness of the model, which was originally estimated based on Phase I data, against all data. Then we assessed the longevity of the humoral response and identified factors that influence these dynamics. We estimated a half-life of the long-lived ASC of at least 15 years and found an influence of geographic region, sex, and age on the humoral response dynamics, with longer antibody persistence in Europeans and women and higher production of antibodies in younger participants.

The Efficacy and Safety of Heterologous Immunization with Pfizer-BioNTech (Pfizer) to Individuals Who Have Completed A Primary Vaccination Schedule with Sinopharm (BBibp-CorV)

The aim of this study was to examine the effectiveness and potential adverse reactions when providing a different Pfizer-BioNTech booster shot to 235 volunteers who had previously received the BBIBP-CorV Sinopharm primary vaccination series. Between February and December 2022, a questionnaire-based cross-sectional study was conducted in Duhok, located within the Kurdistan Region of Iraq. The individuals included in the study were adults aged 18 and above, who had received a Pfizer-BioNTech booster shot following the completion of a two-dose vaccination regimen with Sinopharm (BBIBP-CorV). The findings revealed that among those vaccinated with BBIBP-CorV, there were breakthrough infections at a rate of 4.26%, and no significant correlation was identified between post-vaccination infections and factors such as demographics or medical history. Furthermore, individuals who had a Pfizer booster dose experienced breakthrough infections at a rate of 5.73%, and similarly, no link was discovered between this rate and demographic or medical factors. Additionally, the study uncovered that participants commonly experienced side effects, primarily consisting of mild effects at the injection site. The study implies that both the Sinopharm and Pfizer vaccines demonstrate satisfactory safety profiles. It also suggests that giving a heterologous booster dose to individuals who have finished their primary vaccination with the BBIBP-CorV vaccine offers a significant level of protection against infection.

Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination

Since the emergence of SARS-CoV-2, vaccines targeting COVID-19 have been developed with unprecedented speed and efficiency. CoronaVac, utilising an inactivated form of the COVID-19 virus and the mRNA26 based Pfizer/BNT162b2 vaccines are widely distributed. Beyond the ability of vaccines to induce production of neutralizing antibodies, they might lead to the generation of antibodies attenuating the disease by recruiting cytotoxic and opsonophagocytic functions. However, the Fc-effector functions of vaccine induced antibodies are much less studied than virus neutralization. Here, using systems serology, we follow the longitudinal Fc-effector profiles induced by CoronaVac and BNT162b2 up until five months following the two-dose vaccine regimen. Compared to BNT162b2, CoronaVac responses wane more slowly, albeit the levels remain lower than that of BNT162b2 recipients throughout the entire observation period. However, mRNA vaccine boosting of CoronaVac responses, including response to the Omicron variant, induce significantly higher peak of antibody functional responses with increased humoral breadth. In summary, we show that vaccine platform-induced humoral responses are not limited to virus neutralization but rather utilise antibody dependent effector functions. We demonstrate that this functionality wanes with different kinetics and can be rescued and expanded via boosting with subsequent homologous and heterologous vaccination.

Prevalence, risk factors, and vaccine effectiveness of COVID-19 infection in thai children, adolescents, and young adults in the omicron era.

The study of prevalence, risk factors, and vaccine effectiveness (VE) in children, adolescents, and young adults during the Omicron era has been limited, making this the objectives of the study. A prospective, test-negative case-control study was conducted on patients aged 0-24 years old classified as patients under investigation (PUI) from January to May 2022. PUI with positive RT-PCR within 14 days were classified as cases, whilst PUI with negative RT-PCR in 14 days were controls. Univariate and multivariate analyses determined risk factors; VE was calculated using [1-adjusted odds ratio (OR)] × 100. The final analyses included 3,490 patients with a PUI infection rate of 45.6%. Heterologous vaccination regimens, including inactivated vaccines, viral vectors, and mRNA were utilized during the study period. A total of 2,563 patients (73.5%) had received at least 2 vaccine doses, regardless of regimen. Male gender and household infections were independent risk factors for the development of infection, with an adjusted OR of 1.55 and 1.45, respectively. Underlying comorbidities and obesity were not significantly associated with the development of infection. Patients with underlying comorbidities were more likely to have at least moderate severity of infection with the adjusted OR of 3.07. Age older than 11 years was associated with lower infection risk and development of at least moderate infection with adjusted OR of 0.4 and 0.34, respectively. Vaccinated participants also had a lower risk of developing at least moderate infection: adjusted OR of 0.40. The adjusted VE of any vaccination regimen for infection prevention for one, two, three, or more than four doses was 21.8%, 30.6%, 53.5%, and 81.2%, respectively. The adjusted VE of any vaccination regimen for prevention of at least moderate severity of the disease for one, two, three, or more than four doses was 5.7%, 24.3% 62.9%, and 90.6%, respectively. Disease prevalence among PUI was substantially high during the Omicron wave. A two-dose vaccination regimen does not appear sufficient to ensure protection against infection.

Comparing hybrid and regular COVID-19 vaccine-induced immunity against the Omicron epidemic

Evidence on the effectiveness of COVID-19 vaccines among people who recovered from a previous SARS-CoV-2 infection is warranted to inform vaccination recommendations. Using the territory-wide public healthcare and vaccination records of over 2.5 million individuals in Hong Kong, we examined the potentially differential risk of SARS-CoV-2 infection, hospitalization, and mortality between those receiving two homologous doses of BNT162b2 or CoronaVac versus those with a previous infection receiving only one dose amid the Omicron epidemic. Results show a single dose after a SARS-CoV-2 infection is associated with a lower risk of infection (BNT162b2: adjusted incidence rate ratio [IRR] = 0.475, 95% CI: 0.410–0.550; CoronaVac: adjusted IRR = 0.397, 95% CI: 0.309–0.511) and no significant difference was detected in the risk of COVID-19-related hospitalization or mortality compared with a two-dose vaccination regimen. Findings support clinical recommendations that those with a previous infection could receive a single dose to gain at least similar protection as those who received two doses without a previous infection.

The Waning of BNT162b2 Vaccine Effectiveness for SARS-CoV-2 Infection Prevention over Time: A Test-Negative Study in Health Care Professionals of a Health Department from January 2021 to December 2021.

The duration of protection of vaccines against SARS-CoV-2 infection has been evaluated in previous studies, but uncertainty remains about the persistence of effectiveness over time and the ideal timing for booster doses. Therefore, the aim of this study was to evaluate BNT162b2 vaccine effectiveness against SARS-CoV-2 infection in health care workers (HCWs) at a tertiary hospital depending on time elapsed since the completion of a two-dose vaccination regimen. We conducted a case-control with negative test study between 25 January and 12 December 2021 that included 1404 HCWs who underwent an active infection diagnostic test (AIDT) to rule out SARS-CoV-2 infection due to COVID-19 suspicion or prior close contact with patients diagnosed with COVID-19. The adjusted vaccine effectiveness (aVE) for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccination regimen was 91.9%. Then, aVE decreased to 63.7% between 121 to 240 days after completing the full two-dose regimen and to 37.2% after 241 days since the second dose. Vaccination against SARS-CoV-2 infection in HCWs remains highly effective after 12 to 120 days have elapsed since the administration of two doses of the BNT162b2 vaccine; however, effectiveness decreases as time elapses since its administration.

Accelerated DNA vaccine regimen provides protection against Crimean-Congo hemorrhagic fever virus challenge in a macaque model

Crimean-Congo hemorrhagic fever virus (CCHFV) is widely distributed throughout Africa, the Middle East, Southern Asia, and Southern and Eastern Europe. Spread by Hyalomma ticks or by contact with infected animals, CCHF begins non-specifically but can rapidly progress to severe, sometimes fatal, disease. Due to the non-specific early symptoms and often unrecognized infections, patients often present to healthcare systems exhibiting later stages of disease, when treatment is limited to supportive care. Consequently, simple vaccines are critically needed to protect populations at risk of CCHFV infection. Currently, there are no widely approved vaccines for CCHFV. We have previously reported significant efficacy of a three-dose DNA-based vaccination regimen for CCHFV in cynomolgus macaques (Macaca fasicularis). Here, we show that in cynomolgus macaques, plasmid-expressed CCHFV nucleoprotein (NP) and glycoprotein precursor (GPC) antigens elicit primarily humoral and cellular immunity, respectively. We found that a two-dose vaccination regimen with plasmids expressing the NP and GPC provides significant protection against CCHFV infection. Studies investigating vaccinations with either antigen alone showed that plasmid-expressed NPs could also confer protection. Cumulatively, our data show that this vaccine confers robust protection against CCHFV and suggest that both humoral and cellular immunity contribute to optimal vaccine-mediated protection.

Initial protection against SARS-CoV-2 omicron lineage infection in children and adolescents by BNT162b2 in Israel: an observational study

BackgroundThe BNT162b2 (Pfizer-BioNTech) two-dose vaccine regiment for children and the BNT162b2 third dose for adolescents were approved shortly before the SARS-CoV-2 omicron (B.1.1.529) outbreak in Israel. We aimed to estimate the effects of these vaccines on the rates of confirmed infection against the omicron variant in children and adolescents.MethodsIn this observational cohort study, we extracted data for the omicron-dominated (sublineage BA.1) period. We compared rates of confirmed SARS-CoV-2 infection between children aged 5–10 years 14–35 days after receiving the second vaccine dose with an internal control group of children 3–7 days after receiving the first dose (when the vaccine is not yet effective). Similarly, we compared confirmed infection rates in adolescents aged 12–15 years 14–60 days after receiving a booster dose with an internal control group of adolescents 3–7 days after receiving the booster dose. We used Poisson regression, adjusting for age, sex, socioeconomic status, calendar week, and exposure.FindingsBetween Dec 26, 2021, and Jan 8, 2022, we included 1 158 289 participants. In children aged 5–10 years, the adjusted rate of confirmed infection was 2·3 times (95% CI 2·0–2·5) lower in children who received a second dose than in the internal control group. The adjusted infection rate in children who received a second dose was 102 infections per 100 000 risk-days (94–110) compared with 231 infections per 100 000 risk-days (215–248) in the corresponding internal control cohort. In adolescents aged 12–15 years, the booster dose decreased confirmed infection rates by 3·3 times (2·8–4·0) compared with in the internal control group. The adjusted infection rate of the booster cohort was 70 per 100 000 risk-days (60–81) compared with 232 per 100 000 risk-days (212–254) in the internal control cohort.InterpretationA recent two-dose vaccination regimen with BNT162b2 and a recent booster dose in adolescents substantially reduced the rate of confirmed infection compared with the internal control groups. Future studies are needed to assess the duration of this protection and protection against other outcomes such as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 and long-COVID.FundingNone.

The effectiveness of mRNA vaccines to prevent SARS-CoV-2 infection and hospitalisation for COVID-19 according to the time elapsed since their administration in health professionals in the Valencian Autonomous Community (Spain)

The objective was to understand the effectiveness of the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 in health professionals(HPs) in the Valencian Autonomous Community(Spain) who had completed a full vaccination regimen, both in terms of preventing infections and avoiding hospitalisations, according to the time elapsed since the vaccine administration.Case-controlled study with negative test results. HPs who had undergone at least one PCR or antigen(Ag) active infection diagnostic test(AIDT) to rule out SARS-CoV-2 infection between 25 January and 18 July 2021 were included. HPs with positive AIDT result were considered as cases and those with a negative result controls. Adjusted vaccine effectiveness(VEa) to prevent SARS-CoV-2 infection and its 95% confidence interval(95% CI) were calculated using the formula VEa = (1 − OR) × 100.The VEa for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccine regimen was 91.6%(95%CI[89.6%,93.2%]) for the BNT162b2 vaccine and 95.2%(95%CI[88.3%,98.1%]) for the mRNA-1273 vaccine. After 120 days the VEa was 71.5%(95%CI[67.0%,75.5%]) for the BNT162b2 vaccine and 88.3%(95%CI[75.7,94.4%]) for the mRNA-1273 vaccine. The VEa for prevention of hospitalisation for COVID-19 for the complete two-dose regimen of mRNA vaccines (BNT162b2 and mRNA-1273) was 96.8%(95%CI[76.1%,99.6%]).The administration of the complete regimen of the BNT162b2 and mRNA-1273 vaccine against SARS-CoV-2 was highly effective for the prevention of COVID-19 cases in HPs when 12 to 120 days had elapsed since the second dose. However, said effectiveness decreased as time from the vaccine administration elapsed, although it was maintained for the prevention of hospitalisation of HPs.

Protection against Marburg Virus and Sudan Virus in NHP by an Adenovector-Based Trivalent Vaccine Regimen Is Correlated to Humoral Immune Response Levels.

The Marburg virus (MARV) and Sudan virus (SUDV) belong to the filovirus family. The sporadic human outbreaks occur mostly in Africa and are characterized by an aggressive disease course with high mortality. The first case of Marburg virus disease in Guinea in 2021, together with the increased frequency of outbreaks of Ebola virus (EBOV), which is also a filovirus, accelerated the interest in potential prophylactic vaccine solutions against multiple filoviruses. We previously tested a two-dose heterologous vaccine regimen (Ad26.Filo, MVA-BN-Filo) in non-human primates (NHP) and showed a fully protective immune response against both SUDV and MARV in addition to the already-reported protective effect against EBOV. The vaccine-induced glycoprotein (GP)-binding antibody levels appear to be good predictors of the NHP challenge outcome as indicated by the correlation between antibody levels and survival outcome as well as the high discriminatory capacity of the logistic model. Moreover, the elicited GP-specific binding antibody response against EBOV, SUDV, and MARV remains stable for more than 1 year. Overall, the NHP data indicate that the Ad26.Filo, MVA-BN-Filo regimen may be a good candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks.

Humoral Response to the Third Dose of BNT162b2 COVID-19 Vaccine among Hemodialysis Patients

Background: Hemodialysis patients are at high risk for severe COVID-19 disease. Despite a high early seropositivity rate, dialysis patients mount a dampened immune response following two doses of an mRNA vaccine. This study aimed to evaluate the serologic response to a booster dose of BNT162b2 vaccine, 6 months after the second dose, among hemodialysis patients. Methods: This prospective study included 80 hemodialysis patients and 56 healthcare workers serving as controls. Serologic samples were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were the seropositivity rate and the log-transformed anti-SARS-COV-2 S1 (RBD) IgG as a continuous variable after the third dose. Secondary outcomes were the proportion of participants with “high response,” defined as antibody levels >1,000 AU/mL, and “robust response,” defined as antibody levels >4,160 AU/mL, according to prespecified cutoff values associated with neutralizing antibodies. Univariate and multivariate analyses were conducted to identify predictors of antibody response. Results: Among 80 hemodialysis patients, seropositivity rates improved from 78% (62/80) before the third dose, up to 96% (77/80) after the booster dose. The S1-RBD log-transformed antibody level increased significantly following the third dose from 2.15 ± 0.75 to 3.99 ± 0.83 compared with 2.65 ± 0.4 to 4.31 ± 0.42 in the control group. Among the hemodialysis patients, 88% (70/80) became “high responders” (>1,000 AU/mL), and of these, 79% (63/80) mounted a “robust response” (>4,160 AU/mL). Baseline antibody level, dialysis therapy, and hypoalbuminemia were independent predictors of impaired antibody response. Conclusions: A third dose of BNT162b2 COVID-19 vaccine, 6 months after the standard two-dose vaccination regimen, substantially improved humoral response in hemodialysis patients.

Protectivity of COVID-19 Vaccines and Its Relationship with Humoral Immune Response and Vaccination Strategy: A One-Year Cohort Study.

This prospective cohort study aimed to evaluate the efficacy of COVID-19 vaccine schemes, homologous versus heterologous vaccine strategies, and vaccine-induced anti-S-RBD-IgG antibody response in preventing COVID-19 among 942 healthcare workers 1 year after vaccination with the inactivated and/or mRNA vaccines. All participants received the first two primary doses of vaccines, 13.6% of them lacked dose 3, 50.5% dose 4, and 90.3% dose 5. Antibody levels increased with the increase in number of vaccine doses and also in heterologous vaccine regimens. In both inactive, mRNA vaccines and mixed vaccination, infection rates were significantly higher in two-dose-receivers, but lower in four- or five-dose receivers and increasing the total number of vaccine doses resulted in more protection against infection: the three-dose regimen yielded 3.67 times more protection, the four-dose 8 times, and five-dose 27.77 times more protection from COVID-19 infection, compared to any two-dose vaccination regimens. Antibody levels at the end of the first year of four- or five-dose-receivers were significantly higher than two- or three-dose receivers. To conclude, an increased number of total vaccine doses and anti-S-RBD antibody levels increased the protection from COVID-19 infection. Therefore, four or more doses are recommended in 1 year for effective protection, especially in risk groups.

Immunogenicity induced by two and three doses of the BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic diseases and immunocompetent controls: a longitudinal multicentre study

ObjectivesTo evaluate long-term kinetics of the BNT162b2 mRNA vaccine-induced immune response in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD) and immunocompetent controls.MethodsA prospective multicentre study investigated serum anti-SARS-CoV-2 S1/S2...

SARS-CoV-2 Antibody Response against Mild-to-Moderate Breakthrough COVID-19 in Home Isolation Setting in Thailand.

Background: In December 2021, Omicron replaced Delta as the dominant coronavirus disease 2019 (COVID-19) variant in Thailand. Both variants embody diverse epidemiological trends and immunogenicity. We investigated whether Delta and Omicron patients’ biological and clinical characteristics and immunogenicity differed post-COVID-19 infection. Methods: This retrospective cohort study investigated the clinical outcomes and laboratory data of 5181 patients with mild-to-moderate COVID-19 (Delta, 2704; Omicron, 2477) under home isolation. We evaluated anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in 495 individuals post-COVID-19 infection during the Delta pandemic. Results: Approximately 84% of all patients received favipiravir. The median cycle threshold (Ct) values were lower for Omicron patients than Delta patients (19 vs. 21; p < 0.001), regardless of vaccination status. Upper respiratory tract symptoms were more frequent with Omicron patients than Delta patients. There were no significant associations between Ct and Omicron symptoms (95% confidence interval 0.98–1.02). A two-dose vaccine regimen reduced hospital readmission by 10% to 30% and death by under 1%. Anti-RBD IgG and sVNT against Delta were higher among older individuals post-COVID-19 infection. Older individuals expressed anti-RBD IgG and sVNT for a more extended period after two-dose vaccination than other age groups. Conclusions: After a full vaccination course, breakthrough mild-to-moderate Delta and Omicron infections have limited immunogenicity. Prior infections exert reduced protection against later reinfection or infection from novel variants. However, this protection may be sufficient to prevent hospitalization and death, particularly in countries where vaccine supplies are limited.

Booster COVID-19 vaccination against the SARS-CoV-2 Omicron variant: A systematic review

ABSTRACT There is a wealth of data suggesting that the effectiveness of existing vaccines against the Omicron variant, the most mutated SARS-CoV-2 variant to date, has been substantially reduced if only primary vaccination is administered. Therefore, the effectiveness of booster vaccination against the Omicron variant has become a topic of current interest. We conducted a comprehensive search in PubMed, Embase, and the Cochrane Library to collect various pseudovirus neutralization tests or live virus neutralization tests for the Omicron variant, with serum specimens from booster vaccinees. We extracted neutralization titers for the Omicron variant, the original strain, and the other variants before and after booster vaccination, and then manually calculated the fold increase or decrease in neutralization titers for the Omicron variant relative to the other variants, and the fold increase in neutralization titers for the Omicron variant after booster vaccination compared with that before booster vaccination. In the two-dose vaccination regimen, the neutralization titers against the Omicron variant decreased substantially compared to the original strain and other variants. However, after booster vaccination, both homologous and heterologous booster vaccination, the neutralization of serum antibodies against the Omicron variant was significantly improved, although still lower than that of the original strain and other variants. The booster vaccination program based on existing vaccines can produce broad but incomplete immunity against the Omicron variant.