Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study

Abstract

BackgroundPatients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.ObjectivesTo determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.MethodsParticipants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.ResultsFollowing a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).ConclusionThese data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.

Changing Patterns of SARS-CoV-2 Seroprevalence: A Snapshot among the General Population in Kuwait

“…Overall, we found a 95% prevalence of previously vaccinated participants who developed IgG. These data are consistent with seroconversion rates previously observed in published reports [ 37 , 41 , 42 ]. For both vaccines, we noted that IgG titers decreased over time after vaccination.…”

“…This result is similar to other serological surveys conducted in Gulf Cooperation Council countries [ 19 , 21 , 28 , 36 ] and could be attributed to the confined work camps, housing conditions with shared accommodation, and poor adherence to social distance to avoid SARS-CoV-2 infection [ 19 , 36 ]. No significant differences in humoral responses between individuals who received ChAdOx1-nCoV-19/AstraZeneca and BioNTech162b2/Pfizer after two doses of vaccine were found, which appears to be consistent with previous studies [ 37 , 38 ]. Nevertheless, it appears that the ChA-dOx1-nCoV-19/AstraZeneca vaccine may induce higher levels of specific T cells, whereas mRNA vaccines may induce higher antibody titers [ 39 , 40 ].…”

Long-Term Immunological Memory of SARS-CoV-2 Is Present in Patients with Primary Antibody Deficiencies for up to a Year after Vaccination

“…Overall, the long-term durability of the antibody response is poorly understood, with several studies showing a trend toward decreasing antibody levels over time in immunocompetent individuals [ 19 , 20 , 21 , 22 ] while the receptor-binding domain (RBD) of the spike protein-specific memory B-cell fraction persists [ 23 ]. This trend of decrease in antibody levels has also been observed 6 months after the vaccination in primary antibody deficiency patients [ 24 ]. Furthermore, a limited neutralizing capacity of anti-spike SARS-CoV-2 antibodies has been reported in these patients [ 25 , 26 ].…”

Varying Cellular Immune Response against SARS-CoV-2 after the Booster Vaccination: A Cohort Study from Fukushima Vaccination Community Survey, Japan

“…In detail, the proportion of individuals with activated cellular immunity in this study was approximately 10–20 points higher than that of individuals after two vaccination doses (47.5% (N = 95) [ 35 ], 54% (N = 13) [ 36 ], 46.2% (N = 91) [ 37 ]), as well as five points higher than that of those having received booster vaccination (59.6% (N = 47) [ 38 ]). Furthermore, ELISpot tests showed an increase in cellular responses after booster vaccination [ 35 , 38 , 39 , 40 ]. Hence, these findings suggested that booster vaccination induced cellular immunity.…”