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Background There are limited data on whether hybrid immunity differs by count and order of immunity-conferring events (infection with severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] or vaccination against coronavirus disease 2019 [COVID-19]). From a multi-site cohort of frontline workers, we examined the heterogeneity of the effect of hybrid immunity on SARS-CoV-2 antibody levels. Methods Exposures included event count and event order, categorized into 7 permutations. Outcome was level of serum antibodies against receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein (total RBD-binding immunoglobulin). Means were examined up to 365 days after each of the first to seventh events. Results Analysis included 5793 participants measured from 7 August 2020 to 15 April 2023. Hybrid immunity from infection before 1 or 2 vaccine doses elicited modestly superior antibody responses after the second and third events (compared with infections or vaccine doses alone). This superiority was not repeated after additional events. Among adults infected before vaccination, adjusted geometric mean ratios (95% confidence interval [CI]) of anti-RBD early response (versus vaccinated only) were 1.23 (1.14–1.33), 1.09 (1.03–1.14), 0.87 (.81–.94), and 0.99 (.85–1.15) after the second to fifth events, respectively. Post-vaccination infections elicited superior responses; adjusted geometric mean ratios (95% CI) of anti-RBD early response (versus vaccinated only) were 0.93 (.75–1.17), 1.11 (1.06–1.16), 1.17 (1.11–1.24), and 1.20 (1.07–1.34) after the second to fifth events, respectively. Conclusions Evidence of heterogeneity in antibody levels by permutations of infection and vaccination history could inform COVID-19 vaccination policy. [ABSTRACT FROM AUTHOR]

Background Data on antibody kinetics are limited among individuals previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). From a cohort of healthcare personnel and other frontline workers in 6 US states, we assessed antibody waning after messenger RNA (mRNA) dose 2 and response to dose 3 according to SARS-CoV-2 infection history. Methods Participants submitted sera every 3 months, after SARS-CoV-2 infection, and after each mRNA vaccine dose. Sera were tested for antibodies and reported as area under the serial dilution curve (AUC). Changes in AUC values over time were compared using a linear mixed model. Results Analysis included 388 participants who received dose 3 by November 2021. There were 3 comparison groups: vaccine only with no known prior SARS-CoV-2 infection (n = 224); infection prior to dose 1 (n = 123); and infection after dose 2 and before dose 3 (n = 41). The interval from dose 2 and dose 3 was approximately 8 months. After dose 3, antibody levels rose 2.5-fold (95% confidence interval [CI] = 2.2–3.0) in group 2 and 2.9-fold (95% CI = 2.6–3.3) in group 1. Those infected within 90 days before dose 3 (and median 233 days [interquartile range, 213–246] after dose 2) did not increase significantly after dose 3. Conclusions A third dose of mRNA vaccine typically elicited a robust humoral immune response among those with primary vaccination regardless of SARS-CoV-2 infection >3 months prior to boosting. Those with infection <3 months prior to boosting did not have a significant increase in antibody concentrations in response to a booster. [ABSTRACT FROM AUTHOR]

In this review B cell responses in HIV-infected individuals are summarized together with the techniques used to date to produce human monoclonals to HIV and the properties of these antibodies. Profound disturbances in B cell responses are apparent both in vivo and in vitro. While there is evidence in vivo of marked polyclonal B cell activation, primary and secondary antibody responses are impaired. Similarly these cells exhibit spontaneous immunoglobulin secretion upon in vitro culture but do not readily respond to B cell mitogens and recall antigens including HIV. Furthermore, certain of these defects can be reproduced in normal B cells in vitro by incubation with HIV or HIV coded peptides. Individuals infected with HIV develop antibodies to HIV structural proteins (e.g. p17, p24, gp41 and gp120) and regulatory proteins (e.g. vif, nef, RT). Autoantibodies against a number of immunologically important molecules are also frequently observed. The anti- HIV antibodies are predominantly of the IgO1 isotype and exhibit a variety of effects on the virus in vitro. To date, using conventional immortalization strategies, an appreciable number of human monoclonals to HIV have been developed. These have been specific for gp41, gp120 and gag with antibodies of the former specificity predominating. The majority of these antibodies have been of the IgG I isotype. Only a small number of the antibodies neutralize virus in vitro and most of these react with gp 120. The neutralizing antibodies recognize conformational and carbohydrate epitopes or epitopes in amino acid positions 306-322. The predominant epitopes recognized by the anti-gp41 antibodies were in amino acid positions 579-620 and 644-662. A high percentage (≏ 25%) of these antibodies enhance viral growth in vitro. The problems relating to the production of human monoclonals to HIV are discussed together with strategies that could be used in the future. [ABSTRACT FROM AUTHOR]

The monoclonal antibody HNK- l identifies a subpopulation of lymphocytes containing almost all of the natural killer (NK) and antibody-dependent killer (K) cell activity. Using an immunoperoxidase technique on frozen tissue sections of human spleen. tonsil and lymph node we have demonstrated that cells identified by this antibody arc almost exclusively confined to germinal centres. Comparison with the distribution of B cells. T cells and T cell subsets underlines the distinctive distribution of these cells for which a physiological rule in the maturation of antibody affinity during immune responses is suggested. [ABSTRACT FROM AUTHOR]

The effect of human α2-macroglobulin on the recovery of the humoral immune response in X-irradiated mice has been assessed by measurement of antibody- forming cells in the spleen 5 days after challenge with sheep erythrocytes. The capacity of this protein to promote the recovery of immune responsiveness was variable, and appeared to be influenced by the strain and sex of the mice, and the dose of α2M given. [ABSTRACT FROM AUTHOR]

The association of alpha2-macroglobulin (α2M) with the surface membranes of human peripheral blood lymphocyte preparations has been investigated by the direct immunofluorescent technique. The percentage (and total number) of lymphocytes with detectable α2M on their surface is significantly increased in chronic lymphocytic leukaemia. The incidence of α2 M-positive cells in normal and pathological conditions closely parallels that observed with conjugated antiserum to the K and 2 light chains of human immunoglobulin. It bears no relationship however to the plasma α2M levels or to the age of the donor. Additional blocking studies with aggregated human igG, soluble antigen-antibody complexes and the F(ab')2 moiety of the anti-α2M, and indirect immunofluorescent studies with the latter, indicate that the fluorescence observed is not due to interaction of the con- jugated reagent with Fc or C3 receptors. [ABSTRACT FROM AUTHOR]

Antilymphocytic globulin (ALG) depressed the antibody responses of mice to SRBC as measured in terms of splenic PFCs of IgM, IgG1, IgG2a and IgG2b specificity. This effect was apparent over a range of antigen does. ALG also reduced the antibody responses of congenitally athymic mice to SRBC and SHI. The possible mode of action of ALG is discussed in the light of these, and other, observations. [ABSTRACT FROM AUTHOR]

Methods are described for the intravenous administration of equine antilymphocytic globulin (ALG) lo renal transplant recipients, the development of circulating antibodies to the equine IgG has been investigated using primary and secondary immunological procedures. The need for primary immunoassay procedures to assess both the immune response and induction of tolerance to equine IgG in ALG treated patients is extensively discussed. [ABSTRACT FROM AUTHOR]

This article focuses on some factors influencing the ability of anti-lymphocytic antibody to suppress humoral antibody formation. As studies on factors influencing the immunosuppressive activity of anti-lymphocytic antibody are essential in order that people might understand its mode of action. Researchers have previously shown that anti-lymphocytic antibody suppresses cell mediated immune processes prolonging homograft survival, even when administered several after grafting. Experiments have, therefore been performed to determine if anti-lymphocytic antibody was capable of suppressing humoral antibody formation in animals which had received antigenic stimulation shortly before the commencement of anti-lymphocytic antibody treatment.