scholarly journals Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study

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.

2022 ◽  
Author(s):  
Kapil K. Saharia ◽  
Jennifer S. Husson ◽  
Silke V. Niederhaus ◽  
Thierry Iraguha ◽  
Stephanie V. Avila ◽  
...  

BACKGROUND: Solid organ transplant recipients (SOTR), who typically receive post-transplant immunosuppression, show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines in SOTR can overcome the reduced immune responsiveness against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants. METHODS: We performed a prospective cohort study of 53 SOTR receiving SARS-CoV-2 vaccination into a prospective cohort study performing detailed immunoprofiling of humoral immune responses against SARS-CoV-2 and its variants. RESULTS: Prior to the additional vaccine dose, 60.3% of SOTR showed no measurable neutralization and only 18.9% demonstrated neutralizing activity of >90% following two vaccine doses. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titers against microbial recall antigens were in fact higher. In contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titers against SARS-CoV-2 and its delta variants. Vaccinated SOTR showed a markedly fewer linear B cell epitopes, indicating reduced B cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titers and neutralizing activity across alpha, beta and delta variants. However, we observed a significant decrease in anti-spike antibody titers with the omicron variant. CONCLUSIONS: Only a small subgroup of SOTR generated functionally relevant antibodies after completing the initial vaccine series based on dysfunctional priming of immune responses against novel antigens. An additional dose of the vaccine results in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron.


2010 ◽  
Vol 17 (12) ◽  
pp. 1868-1874 ◽  
Author(s):  
Clayton Harro ◽  
Robert Betts ◽  
Walter Orenstein ◽  
Eun-Jeong Kwak ◽  
Howard E. Greenberg ◽  
...  

ABSTRACT Merck V710 is a novel vaccine containing the conserved Staphylococcus aureus iron surface determinant B shown to be protective in animal models. A phase I, multicenter, double-blind study of the dose range was conducted to assess the immunogenicity and safety of an adjuvanted liquid formulation of V710. A total of 124 adults (18 to 55 years of age) were randomized 1:1:1:1 to receive one 0.5-ml intramuscular injection of V710 (5 μg, 30 μg, or 90 μg) or saline placebo. A positive immune response was defined as at least a 2-fold increase in IsdB-specific IgG levels from baseline levels. Local and systemic adverse events were assessed for 5 and 14 days, respectively, following vaccination. Positive immune responses were detected in 12 (67%) of the 18 subjects in the groups receiving 30 and 90 μg V710 tested at day 10. At day 14, a significantly greater proportion of subjects manifested a positive immune response with higher geometric mean concentrations in the V710 30-μg (86%; geometric mean concentration of 116 μg/ml) and 90-μg (87%; geometric mean concentration of 131 μg/ml) dose groups than in the V710 5-μg (29%; geometric mean concentration of 51 μg/ml) or placebo (4%; geometric mean concentration of 23 μg/ml) groups. Immune responses were durable through day 84. Subjects <40 and ≥40 years of age had comparable immune responses. The most common adverse events were injection-site pain, nausea, fatigue, and headache, usually of mild intensity. No immediate reactions or serious adverse events were reported. In this first study of V710 in humans, a single 30-μg or 90-μg dose was more immunogenic than the 5-μg dose or placebo. Immune responses were evident by 10 to 14 days after vaccination in most responders.


2021 ◽  
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.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4598-4598
Author(s):  
Piotr Centkowski ◽  
Lidia B. Brydak ◽  
Magdalena Machala ◽  
Ewa Kalinka ◽  
Maria Blasinska-Morawiec ◽  
...  

Abstract Vaccination against influenza is recommended for immunocompromised individuals. However, there is little information concerning the efficacy of vaccination in patients (pts) with non-Hodgkin lymphoma (NHL). The purpose of this study was to assess humoral response to standard intramuscular trivalent subunit influenza vaccine in pts with NHL as compared to healthy subjects. In two consecutive epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 healthy controls were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in the hemagglutination inhibition (HAI) and neuraminidase inhibition (NII) antibody titers were assessed by comparing geometric mean titers and mean fold increases to baseline values and by comparing changes in the HA seroconversion and seroprotection rates. Pts who received influenza vaccine during 2003/2004 season had after one month increases in the geometric mean titers by a factor of 8,64–26,60 for HI and 6,93–12,66 for NI, as compared with respective increases by a factor of 9,12–24,41 and 4,83–10,31 for the healthy controls. At one month after vaccination seroprotection and seroresponse rates were similar in the two groups, ranging from 68,42 to 84,21 % and 71,93 to 94,74 % in NHL and 66,67–82,22 % and 62,22–86,67 % in controls, respectively. After six months, seroprotection and seroresponse rates had decreased in NHL group to 31,91–38,30% and 46,81–72,34%, respectively. Pts who received influenza vaccine during 2004/2005 season had after 1 month increases in the geometric mean titers by a factor of 38,76–41,49 for HI and 26,59–30,31 for NI, as compared with respective increases by a factor of 81,19–104,32 and 52,16–54,52 for the healthy controls. Seroprotection and seroresponse rates were lower in the former group, ranging from 62,11 to 65,26 % and 74,47 to 77,66 %, respectively. After six months, these parameters had decreased to 24,72–31,46% and 57,30–59,55%, respectively. In both studied seasons, pts achieved titres of functional antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. The results of this study indicate that standard influenza vaccination induces sufficient immune responses in pts with NHL. Previous chemotherapy adminstration seems to have no impact on the efficacy of vaccination.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S386-S386
Author(s):  
Ahmad Yanis ◽  
Zaid Haddadin ◽  
Andrew Speaker ◽  
Danya Waqfi ◽  
Rana Talj ◽  
...  

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with increased morbidity and mortality in immunocompromised individuals, including solid organ transplant recipients (SOTR). Despite being excluded from phase 1-3 SARS-CoV-2 vaccine clinical trials, SOTR were identified as high-risk populations and prioritized for vaccination in public health guidelines. We aimed to evaluate the antibody response to two doses of the BNT162b2 (Pfizer-BioNTech) vaccine in SOTR as compared to healthy controls (HC). Methods SOTR and HC scheduled to receive two doses of BNT162b2 vaccine and able to complete required follow-up visits were enrolled. Blood specimens were collected from participants before receiving the first and second doses and 21-42 days after the second dose. Enzyme-linked immunosorbent assay (ELISA) was used to detect immunoglobulin G (IgG) to the SARS-CoV-2 spike receptor-binding domain (RBD). Generalized estimating equations with a working independence correlation structure were used to compare anti-RBD IgG levels between SOTR and HC at each study visit and within each group over time. All models were adjusted for age, sex, and pre-vaccination seroreactivity in the ELISA. Results A total of 54 SOTR and 26 HC were enrolled, with mean (SD) ages of 72 (3.6) and 62 (6.7) years, 61% and 35% were male, and 91% and 88% were white, respectively. The most common organ transplant types were kidney (41%) and liver (37%). All SOTR were receiving calcineurin inhibitors. The median time post-transplantation was 7 years. SOTR had markedly lower mean anti-RBD IgG levels when compared to HC with adjusted mean differences of -0.76 (95%CI: [-1.04, -0.47]; p &lt; 0.001) ELISA units (EU) and -1.35 (95%CI [-1.68, -1.01]; p &lt; 0.001) EU after the first and second doses, respectively (Figure 1). Both groups had a significant increase in anti-SARS-CoV-2 IgG levels after the second dose. However, the magnitude was lower in SOTR, 0.49 (95%CI [0.31, 0.69]; p &lt; 0.001) EU than in HCs, 1.08 (95% CI [0.91, 1.24]; p &lt; 0.001) EU. Figure 1. Anti-SARS-CoV-2 RBD IgG levels in solid organ transplant recipients and healthy controls before receiving the BNT162b2 vaccine (baseline), post-vaccine dose 1, and post-vaccine dose 2. Conclusion Our study showed SOTR mounted weaker humoral immune responses than HC to SARS-CoV-2 vaccines. Given a lower response, SOTR should continue to practice social distancing and masking until data on vaccine efficacy are available in this vulnerable population. Disclosures Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it's a education grant, supported by genetech)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it's a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support


2021 ◽  
Author(s):  
Matthias B. Moor ◽  
Franziska Suter-Riniker ◽  
Michael P. Horn ◽  
Daniel Aeberli ◽  
Jennifer Amsler ◽  
...  

Background B-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation. Methods Patients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by IFN-g release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29). Results Anti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-g; release was detected in 17% of patients and 86% of healthy controls (p<0.001). Only 5% of patients, but 86% of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/ul), and CD4+ lymphocyte count (>653/ul) predicted humoral vaccine response (area under the curve [AUC]: 62% [CI 56-78], 67% [CI 58-80] and 67% [CI 54-79], (positive predictive value [PPV]: 0.76, 0.7 and 0.71). Conclusion This study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)


2014 ◽  
Vol 22 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Juan Carlos Tinoco ◽  
Christine Juergens ◽  
Guillermo M. Ruiz Palacios ◽  
Jorge Vazquez-Narvaez ◽  
Hermann Leo Enkerlin-Pauwells ◽  
...  

ABSTRACTThis open-label multicenter clinical trial conducted in Mexico assessed the immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) in adults ≥50 years of age not previously vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). The PCV13 elicited a robust immune response in this study population, as reflected by the magnitude of fold rises in functional antibody levels measured by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination. Although the prevaccination OPA geometric mean titers (GMTs) for the majority of the serotypes were significantly lower in the 50- to 64-year age group than those in the ≥65-year age group, the postvaccination immune responses were generally similar. The overall immune responses were higher for the majority of the serotypes in the Mexican study population than those in similar adult study populations who received the PCV13 in Europe and the United States. PCV13 was well tolerated, and there were no vaccine-related serious adverse events. In conclusion, PCV13 is safe and immunogenic when administered to adults ≥50 years of age in Mexico and has the potential to protect against vaccine-type pneumococcal disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT01432262.)


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4621
Author(s):  
Helena Linardou ◽  
Nikolaos Spanakis ◽  
Georgia-Angeliki Koliou ◽  
Athina Christopoulou ◽  
Sofia Karageorgopoulou ◽  
...  

Data on the effectiveness and safety of approved SARS-CoV-2 vaccines in cancer patients are limited. This observational, prospective cohort study investigated the humoral immune response to SARS-CoV-2 vaccination in 232 cancer patients from 12 HeCOG-affiliated oncology departments compared to 100 healthcare volunteers without known active cancer. The seropositivity rate was measured 2–4 weeks after two vaccine doses, by evaluating neutralising antibodies against the SARS-CoV-2 spike protein using a commercially available immunoassay. Seropositivity was defined as ≥33.8 Binding-Antibody-Units (BAU)/mL. A total of 189 patients and 99 controls were eligible for this analysis. Among patients, 171 (90.5%) were seropositive after two vaccine doses, compared to 98% of controls (p = 0.015). Most seronegative patients were males (66.7%), >70-years-old (55.5%), with comorbidities (61.1%), and on active treatment (88.9%). The median antibody titers among patients were significantly lower than those of the controls (523 vs. 2050 BAU/mL; p < 0.001). The rate of protective titers was 54.5% in patients vs. 97% in controls (p < 0.001). Seropositivity rates and IgG titers in controls did not differ for any studied factor. In cancer patients, higher antibody titers were observed in never-smokers (p = 0.006), women (p = 0.022), <50-year-olds (p = 0.004), PS 0 (p = 0.029), and in breast or ovarian vs. other cancers. Adverse events were comparable to registration trials. In this cohort study, although the seropositivity rate after two vaccine doses in cancer patients seemed satisfactory, their antibody titers were significantly lower than in controls. Monitoring of responses and further elucidation of the clinical factors that affect immunity could guide adaptations of vaccine strategies for vulnerable subgroups.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15008-15008 ◽  
Author(s):  
J. T. Bryan ◽  
J. F. Smith ◽  
W. Ruiz ◽  
M. K. Brownlow ◽  
M. J. Brown ◽  
...  

15008 Background: Human papillomavirus (HPV) is the causative agent of cervical cancer. The HPV types 6, 11, 16 and 18 quadrivalent L1 virus-like particle (VLP) vaccine has been shown to be highly efficacious in preventing HPV vaccine type-related disease. The HPV A7 species contains types 18, 45 and 59. The A9 species include types 16, 31, 33, 35, 52 and 58. The potential of the vaccine induced antibodies to cross-neutralize infection of pseudovirions (PsV) of HPV types within the A9 and A7 species was evaluated. Methods: Sera from quadrivalent, monovalent HPV 16, or monovalent HPV 18 vaccinees were evaluated. Sera were tested in a multiplexed competitive Luminex Immunoassay (cLIA) against vaccine types to demonstrate HPV type-specific seroconversion. A9 and A7 VLP type cross-reactive binding ability was assessed by a total IgG LIA. HPV L1 and L2 PsV containing secreted alkaline-phosphatase (SEAP) sequences were constructed using native HPV sequences for 16 and 31 and with mammalian codon-optimized sequences for 18 and 45. Demonstrated expression of SEAP was used as an indirect measure of PsV infection of 293TT cells. Results: All subjects seroconverted to high titers against the vaccine HPV types. Cross-reactive antibodies were generated. Quadrivalent vaccinee sera bound to HPV 31, 45, 52 and 58 VLPs. These total IgG titers were 1.5–2 logs lower than the titers to the vaccine types. PsV types 18 and 45 were neutralized using the 18 monovalent and the quadrivalent sera. At month 7, the PsV 18 neutralization titer was ∼1–1.5 logs less than that required for PsV 45 cross-neutralization. Neutralization studies using PsV of the A9 species are in progress. Conclusions: High titers of anti-HPV antibodies are elicited by vaccination with HPV VLP vaccines. These antibodies can prevent in vitro PsV infection of vaccine-HPV types. Cross-reactive, cross-neutralizing antibodies are generated, however at reduced titers compared to the vaccine-specific types. Antibody titers required for cross-protection against non-vaccine types are not known. [Table: see text]


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