B-cell and antibody responses to SARS-CoV-2: infection, vaccination, and hybrid immunity

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 prompted scientific, medical, and biotech communities to investigate infection- and vaccine-induced immune responses in the context of this pathogen. B-cell and antibody responses are at the center of these investigations, as neutralizing antibodies (nAbs) are an important correlate of protection (COP) from infection and the primary target of SARS-CoV-2 vaccine modalities. In addition to absolute levels, nAb longevity, neutralization breadth, immunoglobulin isotype and subtype composition, and presence at mucosal sites have become important topics for scientists and health policy makers. The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell (MBC) and antibody responses in the dynamic interplay of infection- and vaccine-induced immunity. It also provided an opportunity to explore new vaccine platforms, such as mRNA or adenoviral vector vaccines, in unprecedented cohort sizes. Combined with the technological advances of recent years, this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings. In this review, we summarize the key findings of the last 2.5 years regarding infection- and vaccine-induced B-cell immunity, which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

Dynamics of T cell responses to COVID-19 vaccines and breakthrough infection in people living with HIV receiving antiretroviral therapy

“…Of note, receiving a fourth vaccine dose after having experienced a breakthrough SARS-CoV-2 infection enhanced immune responses even further, with neutralizing antibody responses and CD8+ T cell responses reaching levels significantly higher than those observed in SARS-CoV-2 naïve individuals after four doses. This finding is consistent with previous reports describing the superiority of "hybrid" immunity generated through a combination of vaccination and infection [31,32].…”

“…Moreover, the median percentage of spike-specific CD4+ T cells at 6 months post-third vaccine dose in breakthrough cases was a 1.01% (IQR 0.78-1.51), compared to 0.70% (IQR 0.60-1.02) in SARS-CoV-2-naïve participants at this same time point (p=0.03; Figure 3B), while the median percentage of spike-specific CD8+ T cells in breakthrough cases was 1.20% (IQR 0.96-1.55), compared to 0.80% (IQR 0.60-1.02) in SARS-CoV-2 naïve participants at this time point (p=0.002; Figure 3C). 3A and 3C), consistent with prior reports of superior "hybrid" immunity generated by a combination of vaccination and infection [31,32].…”

T-Cell Responses to COVID-19 Vaccines and Breakthrough Infection in People Living with HIV Receiving Antiretroviral Therapy

“…Of note, post-fourth-dose neutralizing antibody titers and CD8+ T-cell responses in PLWH who experienced a breakthrough infection were significantly higher than among SARS-CoV-2-naive PLWH at this same time (p = 0.001 and p = 0.03, respectively; Figures 3A and 3C). This is consistent with prior reports of superior "hybrid" immunity generated by a combination of vaccinations and infections [33,34].…”

Dynamics of Anti-SARS-CoV-2 IgA and IgG Responses and Their Protective Effect against Fatal Disease after Booster COVID-19 Vaccination

“…The phenomenon of a positive impact of booster doses on induced antibody responses was reinforced in cases of a positive history of SARS-CoV-2 infection and/or initial vaccination with an mRNA vaccine. In the literature, it can be seen that, via hybrid immunity, a higher magnitude of antibodies is recorded after booster vaccination doses [ 19 ]. Additionally, homologous vaccination with three doses of mRNA induces higher antibody titers than heterologous vaccination (initially two doses of adenovirus-vector-based vaccine followed by mRNA) [ 20 ].…”