scholarly journals Immunogenicity and safety of the homogenous booster shot of a recombinant fusion protein vaccine (V-01) against COVID-19 in healthy adult participants primed with a two-dose regimen

2021 ◽  
Author(s):  
Yuan Li ◽  
Xin Fang ◽  
Rongjuan Pei ◽  
Renfeng Fan ◽  
Shaomin Chen ◽  
...  
Keyword(s):  
Phase I ◽  
Booster Dose ◽  
Booster Vaccination ◽  
Protein Vaccine ◽  
Wild Type ◽  
Younger Adults ◽  
Humoral Immune ◽  
Adult Participants ◽  
Waning Immunity ◽  
Favorable Safety

Background: Rising concerns over waning immunity and reduction in neutralizing activity against variants of concern (VOCs) have contributed to deploying booster doses by different strategies to tackle the COVID-19 pandemic. Preliminary findings from Phase I and II have shown that V-01, a recombinant fusion protein vaccine against COVID-19, exhibited favorable safety and immunogenicity profiles in 1060 adult participants of both younger and senior age. Herein, we aimed to assess the immunogenicity and safety for a booster dose in participants previously primed with a two-dose 10mcg V-01 regimen (day 0, 21) from phase I trial, providing reassuring data for necessity and feasibility of a homogenous booster dose. Methods: We conducted a single-arm, open-label trial at the Guangdong Provincial Center for Disease Control and Prevention (Gaozhou, China). Forty-three eligible participants who were previously primed 4-5 months earlier with two-dose 10mcg V-01 regimen from phase I trial received booster vaccination. We primarily assessed the immunogenicity post-booster vaccination, measured by RBD-binding antibodies using ELISA and neutralizing activity against wild-type SARS-CoV-2 and emerging variants of concern (VOCs) using neutralization assays. We secondarily assessed the safety and reactogenicity of the booster vaccination. Results: The third dose of V-01 exhibited significant boosting effects of humoral immune response in participants primed with two-dose 10μg V-01 regimen regarding both wild-type SARS-CoV-2 and VOCs. We observed a 60.4-folds increase in neutralizing titres against SARS-CoV-2 of younger adults, with GMTs of 17 (95%CI: 12-23) prior to booster vaccination in comparison to 1017 (95%CI: 732-1413) at day 14 post booster vaccination; and a 53.6-folds increase in that of older adults, with GMTs of 14 (95%CI: 9-20) before booster vaccination in comparison to 729(95%CI: 397-1339) at day 14 post-booster vaccination. The neutralizing titres against SARS-CoV-2 Delta strain also demonstrated a sharp increase from the day of pre booster vaccination to day 14 post booster vaccination, with GMTs of 11 (95%CI:8-15) versus 383 (95%CI:277-531) in younger adults (35.4-folds increase), and 6.5(95%CI: 5-8) versus 300(95%CI:142-631) in older adults (46.0-folds increase), respectively. We also observed a considerable and consistent increase of pseudovirus neutralizing titres against emerging VOCs from day 28 post second vaccination to day 14 post booster vaccination, with GMTs of 206 (95%CI:163-259) versus 607 (95%CI: 478-771) for Alpha strain, 54 (95%CI:38-77) versus 329 (95%CI: 255-425) for Beta strain, 219 (95%CI:157-306) versus 647 (95%CI: 484-865) for Delta strain. Our preliminary findings indicate a homogenous booster dose of V-01 was safe and well-tolerated, with overall adverse reactions being absent or mild-to-moderate in severity, and no grade 3 or worse AEs were related to booster vaccination. Conclusions: A homogenous booster immunization in participants receiving a primary series of two-dose V-01 elicited a substantial humoral immune response against wild-type SARS-CoV-2 and emerging VOCs, along with a favorable safety and reactogenicity profile. Our study provided promising data for a homogenous prime-boost strategy using recombinant protein vaccine to tackle the ongoing pandemic, potentially providing broad protection against emerging VOCs and overcoming waning immunity.

scholarly journals One year landscape of the inactivated virus vaccine triggered RBD-specific IgG, IgM and IgA responses against the Omicron variant

2022 ◽  
Author(s):  
Jun-biao Xue ◽  
Dan-yun Lai ◽  
He-wei Jiang ◽  
Jie Zhou ◽  
Sheng-ce Tao
Keyword(s):  
Virus Vaccine ◽  
Specific Antibody ◽  
Booster Dose ◽  
Protein Microarray ◽  
Booster Vaccination ◽  
Wild Type ◽  
Specific Antibody Response ◽  
Neutralization Activity ◽  
Specific Igg ◽  
One Year

We reported the first map of vaccine stimulated RBD-specific antibody responses (IgG, IgM and IgA) against the Omicron variant. We generated the map using a protein microarray, by analyzing longitudinal sera collected spanning one year from individuals immunized with 3 doses of an inactivated virus vaccine. The IgG response to RBD-Omicron is: 1/3-1/5 that of RBD-wild type; ~6x higher for the booster dose vs. the 2nd dose; and reaches the plateau in about two weeks after the booster dose, then drops ~5x in another two weeks. Similar results were also obtained for IgM and IgA. Because of the high correlation between RBD-specific antibody response and the neutralization activity to authentic virus, we at least indirectly revealed the landscape of antibody protection against the Omicron variant throughout the vaccination stages. Our results strongly support the necessity of booster vaccination. However, post-booster vaccination may need to be considered.

scholarly journals Sequential immunization with SARS-CoV-2 RBD vaccine induces potent and broad neutralization against variants in mice

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuo Song ◽  
Bing Zhou ◽  
Lin Cheng ◽  
Weilong Liu ◽  
Qing Fan ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Booster Dose ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Inactivated Vaccine ◽  
Wild Type ◽  
Broadly Neutralizing Antibodies ◽  
Vaccination Strategies ◽  
Inactivated Vaccines

AbstractThe current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.

scholarly journals Phase I/II Study of Combination Therapy With Sorafenib, Idarubicin, and Cytarabine in Younger Patients With Acute Myeloid Leukemia

2010 ◽  
Vol 28 (11) ◽  
pp. 1856-1862 ◽  
Author(s):  
Farhad Ravandi ◽  
Jorge E. Cortes ◽  
Daniel Jones ◽  
Stefan Faderl ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Phase I ◽  
Myeloid Leukemia ◽  
Wild Type ◽  
Platelet Recovery ◽  
Probability Of Survival ◽  
Target Effect ◽  
Acute Myeloid

Purpose To determine the efficacy and toxicity of the combination of sorafenib, cytarabine, and idarubicin in patients with acute myeloid leukemia (AML) younger than age 65 years. Patients and Methods In the phase I part of the study, 10 patients with relapsed AML were treated with escalating doses of sorafenib with chemotherapy to establish the feasibility of the combination. We then treated 51 patients (median age, 53 years; range, 18 to 65 years) who had previously untreated AML with cytarabine at 1.5 g/m2 by continuous intravenous (IV) infusion daily for 4 days (3 days if > 60 years of age), idarubicin at 12 mg/m2 IV daily for 3 days, and sorafenib at 400 mg orally twice daily for 7 days. Results Overall, 38 (75%) patients have achieved a complete remission (CR), including 14 (93%) of 15 patients with mutated FMS-like tyrosine kinase-3 (FLT3; the 15th patient had complete remission with incomplete platelet recovery [CRp]) and 24 (66%) of 36 patients with FLT3 wild-type (WT) disease (three additional FLT3-WT patients had CRp). FLT3-mutated patients were more likely to achieve a CR than FLT3-WT patients (P = .033). With a median follow-up of 54 weeks (range, 8 to 87 weeks), the probability of survival at 1 year is 74%. Among the FLT3-mutated patients, 10 have relapsed and five remain in CR with a median follow-up of 62 weeks (range, 10 to 76 weeks). Plasma inhibitory assay demonstrated an on-target effect on FLT3 kinase activity. Conclusion Sorafenib can be safely combined with chemotherapy, produces a high CR rate in FLT3-mutated patients, and inhibits FLT3 signaling.

Belief in a Just World and the Perceived Injustice of Dying Young or Old

2003 ◽  
Vol 47 (4) ◽  
pp. 313-326 ◽  
Author(s):  
Alison L. Chasteen ◽  
Scott F. Madey
Keyword(s):  
Older Adults ◽  
Medical Decision Making ◽  
Medical Decision ◽  
Just World ◽  
Perceived Injustice ◽  
Younger Adults ◽  
Perceived Justice ◽  
Automobile Accident ◽  
Adult Participants ◽  
Relative Value

We investigated how belief in a just world (i.e., that people get what they deserve) affects the perceived injustice of dying young versus dying old. Younger and older adult participants completed a measure of their just world beliefs and then were randomly assigned to read one of four newspaper articles purportedly about a person who died in an automobile accident. In the articles, both the victim's age (19 or 79) and the victim's outlook on life (concerned about the future or living for today) were varied. Results indicated that participants viewed the death of a younger victim as more unjust than the death of an older victim. Older adults, however, experienced less negative affect than did younger adults when reading the article. Older adults also expressed a higher belief in a just world (BJW) than did younger adults. In addition, BJW was related to perceived justice. Participants with a higher BJW perceived the deaths of both victims as more tragic and unjust than did those with a low BJW. The victim's outlook on life did not affect perceived justice. Implications for medical decision-making, the use of aggressive treatment, and the relative value of youth versus age are discussed.

TLR4 regulates rabies virus-induced humoral immunity through recruitment of cDC2 to lymph organs

2021 ◽  
Author(s):  
Chen Chen ◽  
Chengguang Zhang ◽  
Haoqi Li ◽  
Zongmei Wang ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Humoral Immunity ◽  
Humoral Immune Response ◽  
Critical Role ◽  
Wild Type ◽  
Humoral Immune ◽  
Specific Igg ◽  
Molecular Patterns

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expression of pattern recognition receptors (PRRs) also causes diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not been revealed yet. Based on TLR4-deficient ( TLR4 -/- ) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type-2 dendritic cells (CD8α - CD11b + cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of Tfh cells promotes the proliferation of germinal centre (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4 deficiency ( TLR4 -/- ) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG, compared with that occurred in wild-type (WT) mice. As a consequence, TLR4 -/- mice exhibited higher mortality than WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α + CD11b - ), a subset of cDCs known to induce CD4 + T cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

scholarly journals Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Paolo Bosetti ◽  
Cécile Tran Kiem ◽  
Alessio Andronico ◽  
Juliette Paireau ◽  
Daniel Levy-Bruhl ◽  
...  
Keyword(s):  
Mathematical Models ◽  
Booster Vaccination ◽  
Delta Wave ◽  
Transmission Rates ◽  
Waning Immunity ◽  
Protective Behaviours

Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.

scholarly journals Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review

2021 ◽  
Author(s):  
Kin Israel Notarte ◽  
Israel Guerrero-Arguero ◽  
Jacqueline Veronica Velasco ◽  
Abbygail Therese Ver ◽  
Maria Helena Santos de Oliveira ◽  
...  
Keyword(s):  
Humoral Response ◽  
Serum Levels ◽  
Related Factors ◽  
Post Vaccination ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Waning Immunity ◽  
Antibody Class ◽  
Antibody Decline ◽  
Primary Cycle

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) mRNA vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of literature was performed and a total of 18 studies (N=15,980) were identified and reviewed. The percent difference of means of reported antibody titers were then calculated to determine the decline in humoral response after the peak levels post-vaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6 months post-vaccination. Additionally, results showed that regardless of age, sex, serostatus and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain (RBD) IgG and anti-spike IgG, ranging from 94-95% at 90-180 days and 55-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns (VoCs).

scholarly journals Age Is Not a Barrier: Older Adults With Cancer Derive Similar Benefit in a Randomized Controlled Trial of a Remote Symptom Monitoring Intervention Compared With Younger Adults

2020 ◽  
Vol 27 (1) ◽  
pp. 107327482096887
Author(s):  
Lorinda A. Coombs ◽  
Lee Ellington ◽  
Angela Fagerlin ◽  
Kathi Mooney
Keyword(s):  
Older Adults ◽  
Interactive Voice Response ◽  
Controlled Trial ◽  
Ease Of Use ◽  
Younger Adults ◽  
Symptom Monitoring ◽  
Adult Participants ◽  
Perceived Benefit ◽  
Significant Difference ◽  
Technological Tool

This study investigated a remote symptom monitoring intervention to examine if older participants with cancer received a similar magnitude of benefit compared with younger adults with cancer. We analyzed a longitudinal symptom monitoring intervention for 358 participants beginning a new course of chemotherapy treatment in community and academic oncology practices. The study design was a randomized control trial; participants were randomized to the intervention or usual care, the intervention was delivered during daily automated coaching. Older adults with moderate and severe symptoms derived similar benefit as those adults younger than 60 years of age, adherence to the study protocol which involved daily calls was high. There was no significant difference between the 2 age categories; on average, older adult participants made 88% of expected daily calls and younger adult participants made 90% of expected daily calls. Our results challenge the perception that older adults are unwilling or unable to use a technological tool such as interactive voice response and suggest that patient utilization may be guided by other factors, such as ease of use and perceived benefit from the intervention.

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