Humoral Immune Response Diversity to Different COVID-19 Vaccines: Implications for the “Green Pass” Policy

Abstract

In the COVID-19 pandemic year 2021, several countries have implemented a vaccine certificate policy, the “Green Pass Policy” (GPP), to reduce virus spread and to allow safe relaxation of COVID-19 restrictions and reopening of social and economic activities. The rationale for the GPP is based on the assumption that vaccinated people should maintain a certain degree of immunity to SARS-CoV-2. Here we describe and compare, for the first time, the humoral immune response to mRNA-1273, BNT162b2, Ad26.COV2.S, and ChAdOx1 nCoV-19 vaccines in terms of antibody titer elicited, neutralizing activity, and epitope reactogenicity among 369 individuals aged 19 to 94 years. In parallel, we also considered the use of a rapid test for the determination of neutralizing antibodies as a tool to guide policymakers in defining booster vaccination strategies and eligibility for Green Pass. Our analysis demonstrates that the titer of antibodies directed towards the receptor-binding domain (RBD) of SARS-CoV-2 Spike is significantly associated with age and vaccine type. Moreover, natural COVID-19 infection combined with vaccination results, on average, in higher antibody titer and higher neutralizing activity as compared to fully vaccinated individuals without prior COVID-19. We also found that levels of anti-Spike RBD antibodies are not always strictly associated with the extent of inhibition of RBD-ACE2 binding, as we could observe different neutralizing activities in sera with similar anti-RBD concentrations. Finally, we evaluated the reactivity to four synthetic peptides derived from Spike protein on a randomly selected serum sample and observed that similar to SARS-CoV-2 infection, vaccination elicits a heterogeneous antibody response with qualitative individual features. On the basis of our results, the use of rapid devices to detect the presence of neutralizing antibodies, even on a large scale and repeatedly over time, appears helpful in determining the duration of the humoral protection elicited by vaccination. These aspects and their implications for the GPP are discussed.

An Overview of Current Accomplishments and Gaps of COVID-19 Vaccine Platforms and Considerations for Next Generation Vaccines

“…The diversity of immune responses to SARS-CoV-2 strains during viral infection is associated with multiple factors such as structural and non-structural viral proteins, genetic diversity of MHC Class I and II genes in the population, immune robustness, and co-morbidities of infected individuals 13 , 14 . In healthy individuals, these responses culminate into responses attributed to a mix of CD8 cytotoxic T cells, CD4 effector T cells, and antibody-secreting B cells.…”

Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies

“…The available vaccines induce SARS-CoV-2-specific cellular and antibody responses but a major goal is to induce virus-neutralizing antibodies against the S protein and in particular against the RBD of SARS-CoV-2 [ 28 , 29 ]. Similarly to what is observed after natural infection, it was found that COVID-19 vaccines induce a heterogeneous S-specific antibody response regarding antibody titers and virus neutralizing capacity [ 15 , 30 , 31 ]. Importantly, neutralizing antibodies induced by infection as well as by vaccination were found to decrease after a few months [ 32 , 33 , 34 , 35 ], and accordingly breakthrough infections were noted even after booster vaccinations [ 36 , 37 , 38 ].…”

Humoral immune response after SARS-CoV-2 vaccination in cladribine-treated multiple sclerosis patients

“…No clear cause could be identified, as patients had no relevant comorbidities or comedication, no lymphopenia and both received two vaccination doses. The seronegative patients were somewhat older (53 and 56), which could be a contributing factor since higher age has been associated with a higher probability of low- or non-response to vaccination [21] , [22] . However, the present study finds a similar seropositivity rate as found in studies in large samples from the general population [23] .…”