Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans

Abstract

The Ad26.COV2.S vaccine [1][2][3] has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies 1 . However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase 1/2 clinical trial 2 against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1., and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titers that were 5.0-and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 following vaccination. Median binding antibody titers were 2.9-and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition, and NK cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1, and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.

Anterior Cingulate Cortex Activity During Rest Is Related to Alterations in Pain Perception in Aging

“…More interestingly, rsFC between ACC and pre-and postcentral gyrus was positively correlated with the unpleasantness ratings in response to the pain stimulation in both high and low distraction conditions in the two groups of participants. Supporting our results, several studies have shown a strong relationship between rsFC of ACC and pain perception in healthy young subjects (Boly et al, 2007;Proverbio et al, 2009;Ploner et al, 2010) and in diseases such as Alzheimer's (Beach et al, 2017). Furthermore, it seems that baseline fluctuations in ACC activity could be related to fluctuations in the subjective perception of identical nociceptive stimuli (Boly et al, 2007) and could predict individual pain thresholds (Spisak et al, 2020).…”

“…Furthermore, resting-state functional networks, such as the default mode network (DMN) and the salience network, are altered in both healthy older individuals (Tomasi and Volkow, 2012;Huang et al, 2015) and chronic pain patients (Napadow et al, 2010;Kucyi and Davis, 2015;Martucci and Mackey, 2016). In this sense, it is well known that there is a strong relationship between resting-state functional connectivity (rsFC) of several brain areas belonging to these networks [i.e., anterior cingulate cortex (ACC), insula and amygdala] and pain perception in healthy young subjects (Proverbio et al, 2009;Ploner et al, 2010), as well as in patients with aging-related diseases such as Alzheimer's disease (Beach et al, 2017). Thus, for instance, it has been shown that ACC baseline fluctuations positively correlate with pain intensity ratings after nociceptive stimulation in a healthy population (Boly et al, 2007).…”

“…We hypothesized that older participants would show an increased beta and reduced alpha activity, as well as, a disturbed connectivity of the DMN and the salience networks. Moreover, we expected that the electrophysiological and hemodynamic alterations in pain-related areas, especially ACC (Proverbio et al, 2009;Ploner et al, 2010), would be related to changes in intensity and unpleasantness ratings of painful stimulation.…”

Comparison of Neutralizing Antibody Titers Elicited by mRNA and Adenoviral Vector Vaccine against SARS-CoV-2 Variants

“…The data reported here differ somewhat from those reported by Jongeneelen et al who found that Ad26.COV2.S-elicited antibody titers were mostly maintained against the variants 20 . In addition, Alter et al reported a 5-fold decrease in neutralizing antibody titer against Beta and 3.3-fold decrease against the Gamma variant by the sera from Ad26.COV2.S vaccination 21 which were less pronounced than those reported here. While the studies used similar assays to measure antibody neutralization and analyzed sera collected at a similar time-point post-immunization, it is possible that differences in the study populations accounted for the experimental differences.…”

Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19

“…Overall, these evidences support the concept that a single-dose of an adenoviral vaccine, which is cheap and easy to deploy in a pandemic setting, represents a good tool to effectively prime the immune system, which can be boosted afterwards by a single dose of a different vaccine platform, reaching high levels of immune responses. As preclinical and clinical evidence suggest 6,9 , keeping adenoviral vectored vaccines as part of heterologous vaccination regimens may be the key for optimal induction and persistence of T cell responses, a feature that may confer cross-protection in the context of already circulating and newly emerging SARS-CoV-2 variants 10 . Further prospective and controlled investigations are mandatory to confirm these data and to evaluate the impact of age and the optimal timing between prime and boost as well as the order of administration of the heterologous vaccines.…”