Humoral Responses Against Variants of Concern by COVID-19 mRNA Vaccines in Immunocompromised Patients

Abstract

IMPORTANCEThere are limited comparative data on the durability of neutralizing antibody (nAb) responses elicited by messenger RNA (mRNA) vaccines against the SARS-CoV-2 variants of concern (VOCs) in immunocompromised patients and healthy controls.OBJECTIVE To assess the humoral responses after vaccination with BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines. DESIGN, SETTING, AND PARTICIPANTSIn this prospective, longitudinal monocentric comparative effectiveness study conducted at the Lausanne University Hospital, binding IgG anti-spike antibody and nAb levels were measured at 1 week, 1 month, 3 months, and 6 months after vaccination with mRNA-1273 (24.6% of participants) or BNT162b2 (75.3% of participants).INTERVENTIONS All participants received 2 doses of either mRNA-1273 or BNT162b2 vaccines 4 to 6 weeks apart. MAIN OUTCOMES AND MEASURESThe primary outcome of the study was the persistence of nAb responses against the original, nonvariant SARS-CoV-2 (2019-nCoV) and different VOCs at 6 months after vaccination. Key secondary outcomes were associations of the type of mRNA vaccine, the underlying disease, and the treatment with the response to vaccination. RESULTS Among the 841 participants enrolled between January 14 and August 8, 2021, the patient population comprised 637 participants (mean [SD] age, 61.8 [13.7] years; 386 [60.6%] female), and the healthy control population comprised 204 participants (mean [SD] age, 45.9 [12.0] years; 144 [70.6%] female). There were 399 patients with solid cancers, 101 with hematologic cancers, 38 with solid organ transplants, 99 with autoimmune diseases, and 204 healthy controls. More than 15 000 nAb determinations were performed against the original, nonvariant 2019-nCoV and the Alpha, Beta, Gamma, and Delta variants. The proportions of nAbs and their titers decreased in all study groups at 6 months after vaccination, with the greatest decreases for the Beta and Delta variants. For Beta, the proportion decreased to a median (SE) of 39.2% (5.5%) in those with hematologic cancers, 44.8% (2.7%) in those with solid cancers, 23.1% (8.3%) in those with solid organ transplants, and 22.7% (4.8%) in those with autoimmune diseases compared with 52.1% (4.2%) in healthy controls. For Delta, the proportions decreased to 41.8% (5.6%) in participants with hematologic cancer, 51.9% (2.7%) in those with solid cancers, 26.9% (8.7%) in those with solid organ transplants, and 30.7% (5.3%) in those with autoimmune diseases compared with 56.9% (4.1%) healthy controls. Neutralizing antibody titers decreased 3.5-to 5-fold between month 1 and month 6, and the estimated duration of response was greater and more durable among those participants vaccinated with mRNA-1273. In participants with solid cancers, the estimated duration of nAbs against the Beta variant was 221 days with mRNA-1273 and 146 days with BNT162b2, and against the Delta variant, it was 226 days with mRNA-1273 and 161 with BNT162b2. The estimated duration of nAbs in participants with hematologic cancers was 113 and 127 days ag...

Kinetics of the Neutralizing and Spike SARS-CoV-2 Antibodies following the Sinovac Inactivated Virus Vaccine Compared to the Pfizer mRNA Vaccine in Singapore

“…Thus, the lower antibody titers in immunocompromised/immunosuppressed patients following inactivated virus vaccines would place them at greater risk for COVID-19 breakthrough infection. On the other hand, with two doses of BNT162b2/mRNA-1273 mRNA vaccines, even immunocompromised patients with solid cancers, hematologic cancers, autoimmune diseases, or solid organ transplants could develop high enough rates of seropositivity one month after the second vaccine inoculation (100% of subjects with untreated solid cancers, 98.3% of those with treated solid cancers, and 95% of those with untreated hematologic cancers), conferring some degree of protection against COVID-19 [ 29 ].…”

Interpretation of non-responders to SARS-CoV-2 vaccines using WHO International Standard

“…[49][50] Hence, further clinical trials must be performed to finalize effective booster shots for immunocompromised people after administering the complete dose in the general population. [51][52][53][54][55] According to this study, the anti-spike IgG seropositivities were 99.7% and 98.9% in the 18-59 yr and ≥60 yr groups, respectively. Additionally, certain naïve immune cells, such as CD4 cells, CD8 cells, and B cells exhibited significant waning in the elderly people, suggesting that the non-seroconversion rates were higher in individuals with lower immune cell counts.…”

SARS-CoV-2 Omicron potently neutralized by a novel antibody with unique Spike binding properties

“…Many of the spectacular advances gained in the fight against the pandemics, including COVID-19 vaccines and potent neutralizing mAbs, were largely erased in a matter of months following the emergence of the Delta and Omicron variants. The Omicron variant exhibits markedly reduced sensitivity to vaccine-induced humoral immunity in healthy donors but, more importantly, immunocompromised individual are now almost completely unprotected due to their inability to mount a protective humoral immune response following vaccination 33 . For these vulnerable individuals, we propose that passive immunization through two-to-three injections per year with the extended half-life P2G3 and P5C3 LS mAbs 27 , that can simultaneously bind to highly conserved and distinct epitopes on the viral Spike, represents a very attractive prophylaxis option 34 .…”