scholarly journals Neutralization breadth of SARS CoV-2 viral variants following primary series and booster SARS CoV-2 vaccines in patients with cancer

Author(s):  
Vivek Naranbhai ◽  
Kerri J St. Denis ◽  
Evan C Lam ◽  
Onosereme Ofoman ◽  
Wilfredo F Garcia-Beltran ◽  
...  

Patients with cancer are more likely to have impaired immune responses to SARS CoV-2 vaccines. We studied the breadth of responses against SARS CoV-2 variants followingly primary vaccination in 178 patients with a variety of tumor types, and after booster doses in a subset. Neutralization of alpha, beta, gamma and delta SARS-CoV-2 variants was impaired relative to wildtype (Wuhan), regardless of vaccine type. Regardless of viral variant, mRNA1273 was the most immunogenic, followed by BNT162b2 and then Ad26.COV2.S. Neutralization of more variants (breadth) was associated with higher magnitude of wildtype neutralization, and increase with time since vaccination; increased age associated with lower breadth. Anti-spike binding antibody concentrations were a good surrogate for breadth (PPV=90% at >1000U/ml). Booster SARS-CoV-2 vaccines conferred enhanced breadth. These data suggest that achieving a high antibody titer is desirable to achieve broad neutralization; a single booster dose with current vaccines increases breadth of responses against variants.

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0247216
Author(s):  
Kyra D. Zens ◽  
Vasiliki Baroutsou ◽  
Philipp Sinniger ◽  
Phung Lang

The goal of this study was to evaluate timeliness of Tick-borne Encephalitis vaccination uptake among adults in Switzerland. In this cross-sectional survey, we collected vaccination records from randomly selected adults 18–79 throughout Switzerland. Of 4,626 participants, data from individuals receiving at least 1 TBE vaccination (n = 1875) were evaluated. We determined year and age of first vaccination and vaccine compliance, evaluating dose timeliness. Participants were considered “on time” if they received doses according to the recommended schedule ± a 15% tolerance period. 45% of participants received their first TBE vaccination between 2006 and 2009, which corresponds to a 2006 change in the official recommendation for TBE vaccination in Switzerland. 25% were first vaccinated aged 50+ (mean age 37). More than 95% of individuals receiving the first dose also received the second; ~85% of those receiving the second dose received the third. For individuals completing the primary series, 30% received 3 doses of Encepur, 58% received 3 doses of FSME-Immun, and 12% received a combination. According to “conventional” schedules, 88% and 79% of individuals received their second and third doses “on time”, respectively. 20% of individuals receiving Encepur received their third dose “too early”. Of individuals completing primary vaccination, 19% were overdue for a booster. Among the 31% of subjects receiving a booster, mean time to first booster was 7.1 years. We estimate that a quarter of adults in Switzerland were first vaccinated for TBE aged 50+. Approximately 80% of participants receiving at least one vaccine dose completed the primary series. We further estimate that 66% of individuals completing the TBE vaccination primary series did so with a single vaccine type and adhered to the recommended schedule.


Author(s):  
Vivek Naranbhai ◽  
Claire A. Pernat ◽  
Alexander Gavralidis ◽  
Kerri J. St Denis ◽  
Evan C. Lam ◽  
...  

PURPOSE The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood. METHODS We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti–SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison. RESULTS Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] 2.9, log10 geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; P < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses ( P < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type ( P < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses ( P = .002 for concentration, P = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose). CONCLUSION Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 652
Author(s):  
Alberto Modenese ◽  
Stefania Paduano ◽  
Annalisa Bargellini ◽  
Rossana Bellucci ◽  
Simona Marchetti ◽  
...  

Background: The immunization of healthcare workers (HCWs) plays a recognized key role in prevention in the COVID-19 pandemic: in Italy, the vaccination campaign began at the end of December 2020. A better knowledge of the on-field immune response in HCWs, of adverse effects and of the main factors involved is fundamental. Methods: We performed a study on workers at a nursing home in Northern Italy, vaccinated in January–February 2021 with two doses of the BNT162b2 vaccine four weeks apart, instead of the three weeks provided for in the original manufacturer protocol. One month after the second dose, the serological titer of IgG-neutralizing anti-RBD antibodies of the subunit S1 of the spike protein of SARS-CoV-2 was determined. The socio-demographic and clinical characteristics of the subjects and adverse effects of vaccination were collected by questionnaire. Results: In all of the workers, high antibody titer, ranging between 20 and 760 times the minimum protective level were observed. Titers were significantly higher in subjects with a previous COVID-19 diagnosis. Adverse effects after the vaccine were more frequent after the second dose, but no severe adverse effects were observed. Conclusions: The two doses of the BNT162b2 vaccine, even if administered four weeks apart, induced high titers of anti-SARS-CoV-2 neutralizing IgG in all the operators included in the study.


2010 ◽  
Vol 17 (12) ◽  
pp. 1970-1976 ◽  
Author(s):  
F. M. Russell ◽  
J. R. Carapetis ◽  
C. Satzke ◽  
L. Tikoduadua ◽  
L. Waqatakirewa ◽  
...  

ABSTRACT This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.


PEDIATRICS ◽  
1986 ◽  
Vol 77 (4) ◽  
pp. 471-476
Author(s):  
Harrison C. Stetler ◽  
Walter A. Orenstein ◽  
Roger H. Bernier ◽  
Kenneth L. Herrmann ◽  
Barry Sirotkin ◽  
...  

Two hundred fifty-four infants who had received measles vaccine at &lt;10 months of age were revaccinated at ≥15 months of age, and their immune responses were compared with 129 control infants who received their first doses of measles vaccine at ≥15 months of age. Sera were collected at the time of revaccination (study infants) or primary vaccination (control infants), 3 weeks, and 8 months later and tested for antibody by hemagglutination inhibition (HI), enzymelinked immunosorbent assay (ELISA), and cytopathic effect neutralization (CPEN). Of the 121 study infants who were initially HI negative, 116 (95.9%) made HI antibody 3 weeks postrevaccination compared with 126 (99.2%) of 127 control infants (P = 0.19). Of the 63 study infants with no initial detectable antibody by any of the three tests, 14 (22.2%) had a measles-specific IgM response 3 weeks postrevaccination compared with 37 of 50 (74.0%) randomly chosen control infants. By 8 months after revaccination, the 121 initially HI-negative study infants were significantly less likely to have detectable HI antibodies than control infants (52.1% v 97.6%) (P &lt; .001). However, 96.7% of these 121 study infants had detectable neutralizing antibody 8 months postrevaccination, an antibody thought to correlate best with protection. This study confirms the altered immune response to revaccination in infants first vaccinated prior to 10 months of age; however, the data suggest that most of these infants were successfully primed and are probably protected after revaccination.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2119-2119
Author(s):  
Cornelia Englisch ◽  
Florian Moik ◽  
Stephan Nopp ◽  
Markus Raderer ◽  
Ingrid Pabinger ◽  
...  

Abstract Introduction: Venous thromboembolism (VTE) is common in patients with cancer. Non-O blood type is associated with higher levels of factor FVIII activity and von Willebrand factor compared to blood type O, and has been identified as a risk factor for VTE in the general population. However, the impact of ABO blood type on risk of cancer-associated VTE has not been clarified. Methods: To determine the influence of non-O blood type on risk of cancer-associated VTE, we utilized the dataset of the Vienna Cancer and Thrombosis Study (CATS), which is a single center, prospective observational cohort study including patients with newly diagnosed or recurrent cancer. Patients were followed for objectively diagnosed, independently adjudicated VTE for a maximum of 2 years. VTE was quantified in competing risk analysis, accounting for all-cause mortality as competing outcome event. A proportional sub-hazard regression model according to Fine & Gray was used for between-group comparisons. Based on the violation of the proportional sub-hazard assumption, we explored potential time-dependent effects of non-O blood type on VTE risk in a restricted cubic spline analysis, modeling differences in risk estimates over follow-up time. Further, time-restricted subdistribution hazard ratios (SHR) were obtained specifically for the &lt;3 months and ≥3 months follow-up intervals. In a subgroup analysis, differences in VTE risk according to ABO-blood type were analyzed for patients with very high thrombotic risk tumor types (pancreatic, gastric, glioblastoma), compared to the remainder of patients. Results: In total, 1,708 patients were included in our analysis (46% female, median age: 61 years [interquartile range, IQR: 52-68]). The most common tumor types were lung (19%), breast (16%), and brain (14%) cancer, with 32% of solid tumor patients having metastatic disease at study inclusion. Over a median follow-up of 24 months (IQR: 10-24), 151 patients were diagnosed with VTE (cumulative 2-year incidence: 9.2%, 95% confidence interval [CI]: 7.9-10.7) and 649 patients died (2-year mortality: 38%). Overall, blood type O was present in 38% of patients, A in 40%, B in 15%, and AB in 7%. The cumulative incidence of VTE at 3-, 6-, 12-, and 24-months for patients with blood type O was 3.8% (95% CI: 2.5-5.5), 5.7% (95% CI: 4.1-7.7), 7.0% (95% CI: 5.1-9.1), and 7.6% (95% CI: 5.7-9.9), compared to 3.4% (95% CI: 2.4-4.7), 6.5% (95% CI: 5.1-8.1), 8.4% (95% CI:6.8-10.2), and 10.2% (95% CI: 8.4-12.2) in patients with non-O blood type (Gray´s test: p=0.103, Figure 1). Upon visual inspection of cumulative incidence functions, a violation of the proportional sub-hazard assumption was suspected. In restricted cubic spline analysis, estimating hazard ratio (HR) for VTE of patients with non-O compared to O blood type, a time-varying effect of non-O blood type towards an increased VTE risk was observed (Figure 2). Based on that, time-restricted competing risk regression models were performed. During the first 3 months of follow-up, no differences in VTE risk were found (SHR for non-O vs. O blood type: 1.00, 95% CI: 0.60-1.67, p=0.992). Beyond the first 3-month follow-up, patients with non-O blood type had an increased VTE risk compared to patients with blood type O (SHR 1.79, 95%CI: 1.12-2.85, p=0.015). In a subgroup analysis, no association with VTE risk was found in patients with very high thrombotic risk tumor types (SHR 0.94, 95% CI: 0.55-1.61, p=0.824). In contrast, in patients with low/intermediate risk cancer, non-O blood type was associated with increased risk of VTE (SHR 1.73, 95% CI: 1.09-2.73, p=0.019). Conclusion: Non-O blood type was identified as a time dependent risk factor for cancer-associated VTE. In the first 3 months after study inclusion, characterized as the highest VTE risk period in our cancer cohort, no differences in VTE risk between blood types were found. Afterwards, beyond the first 3 months of follow-up, an increased VTE-risk in non-O blood types was observed, comparably in magnitude to the risk difference in the general non-cancer population. Further, an association of non-O blood type with VTE risk in patients with low/intermediate thrombotic risk cancers was observed, whereas no effect was present in those with very high-risk tumors. These findings indicate non-O blood type as a putative risk factor for VTE in patients with cancer in comparably low thrombotic risk scenarios. Figure 1 Figure 1. Disclosures Pabinger: Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Alexion: Consultancy, Honoraria; Daiichi Sanchyo: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; NovoNordisk: Consultancy, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding.


Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1409
Author(s):  
Wasim A. Prates-Syed ◽  
Lorena C. S. Chaves ◽  
Karin P. Crema ◽  
Larissa Vuitika ◽  
Aline Lira ◽  
...  

Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrating convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, optimized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology.


Author(s):  
Andrew Hastie ◽  
Grégory Catteau ◽  
Adaora Enemuo ◽  
Tomas Mrkvan ◽  
Bruno Salaun ◽  
...  

Abstract Background The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years of age. We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule, by following up adults vaccinated at ≥60 years of age and by modeling, and (2) immunogenicity of 2 additional doses administered 10 years after initial vaccination. Methods Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10 years after initial vaccination, and modeled through 20 years using a Piecewise, Power law and Fraser model. The immunogenicity and safety of 2 additional RZV doses were also evaluated. Results Seventy adults were enrolled. Ten years after initial vaccination, humoral and CMI responses were approximately 6-fold and 3.5-fold, respectively, above those before the initial vaccination levels. Predicted immune persistence through 20 years after initial vaccination was similar across the 3 models. Sixty-two participants (mean age [standard deviation], 82.6 [4.4] years) received ≥1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose. Conclusions Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10 years after the initial 2-dose course. Clinical Trials Registration NCT02735915.


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