Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers.

BACKGROUND: Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. METHODS: We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. FINDINGS: Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. INTERPRETATION: Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. FUNDING: This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the "Centro de Excelencia Severo Ochoa 2019-2023" Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance (contract number HHSN272201400008C). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript.

Influence of episodes of intermittent viremia ("blips") on immune responses and viral load rebound in successfully treated HIV-infected patients.

Presenting episodes of intermittent viremia (EIV) under combination antiretroviral therapy (cART) is frequent, but there exists some controversy about their consequences. They have been described as inducing changes in immune responses potentially associated with a better control of HIV infection. Conversely, it has been suggested that EIV increases the risk of virological failure. A retrospective analysis of a prospective, randomized double-blinded placebo-controlled study was performed. Twenty-six successfully treated HIV-infected adults were randomized to receive an immunization schedule or placebo, and after 1 year of follow-up cART was discontinued. The influence of EIV on T cell subsets, HIV-1-specific T cell immune responses, and viral load rebound, and the risk of developing genotypic mutations were evaluated, taking into account the immunization received. Patients with EIV above 200 copies/ml under cART had a lower proportion of CD4(+) and CD4(+)CD45RA(+)RO(-) T cells, a higher proportion of CD8(+) and CD4(+)CD38(+)HLADR(+) T cells, and higher HIV-specific CD8(+) T cell responses compared to persistently undetectable patients. After cART interruption, patients with EIV presented a significantly higher viral rebound (p=0.007), associated with greater increases in HIV-specific lymphoproliferative responses and T cell populations with activation markers. When patients with EIV between 20 and 200 copies/ml were included, most of the differences disappeared. Patients who present EIV above 200 copies/ml showed a lower CD4(+) T cell count and higher activation markers under cART. After treatment interruption, they showed greater specific immune responses against HIV, which did not prevent a higher virological rebound. EIV between 20 and 200 copies/ml did not have this deleterious effect.

Can the response to 23-valent pneumococcal vaccine in splenectomised patients be predicted?

The 23-valent pneumococcal vaccine has unequal effectiveness in splenectomised patients. We performed a longitudinal study (2005-2008) whose main objective was to characterize the profile of non-responders among splenectomised patients treated at our institution and identify potential predictive indicators of the response to the vaccine. The immune response was evaluated in 96 subjects. The proportion of responders was 70% (95% CI: 60-78%). Immunosuppression (OR=3.19, 95% CI 1.04-9.73) and the reason for splenectomy (hematologic neoplasia versus non-malignant hematologic diseases, OR=7.37, 95% CI 1.71-31.7) were independent predictors of non-response to vaccination. However, the positive predictive value of the model and the likelihood ratio for a positive result were low (PPV=76.6%, 95% CI 66.2-84.4%, LR(+)=1.41, 95% CI 1.08-1.86). We recommend determining the response to pneumococcal vaccine in these patients when possible.

Influence of a vaccination schedule on viral load rebound and immune responses in successfully treated HIV-infected patients.

Vaccination is recommended for HIV-infected patients. Transient increases of viral load (VL) and risk of developing resistance to HAART have been described. In addition, VL rebounds could increase HIV-specific immune responses. Twenty-six successfully treated HIV-infected adults were randomized to receive a vaccination schedule or placebo during 12 months. Afterward, HAART was discontinued. Influences of vaccination over VL, genotypic mutations, different T cell subsets, and HIV-1-specific immune responses were evaluated. Patients did not present any secondary effect. No differences in incidence of detectable VL determinations were detected between groups [relative risk 0.54 (95% CI 0.23-1.26)]. No relevant resistance mutations were detected. The vaccinated group showed a significant drop in CD4(+) T cells (p = 0.046) associated with increases in activated T cells. HIV-1-specific lymphoproliferative responses increased more in the vaccinated group during the vaccination period. Viral rebound dynamics after interrupting HAART were similar in both groups. A vaccination schedule in successfully treated HIV patients was safe, was not associated with an increase in detectable VL, and did not increase the risk of developing resistance mutations. However, it induced an increase in T cell activation and a drop in CD4(+) T cells, although these changes did not influence the VL rebound dynamics after HAART interruption.

[Post-transplantation vaccination of bone-marrow transplant recipients]. / Vacunación de pacientes receptores de trasplante de progenitores hematopoyéticos.

BACKGROUND: Patients subject to bone marrow transplantation (BMT) and other blood stem cell transplantations are severely immunocompromised after transplantation. Some studies have suggested that post-transplantation loss of acquired immunity may play a role. The objective of this study was to determine the susceptibility to vaccine-preventable diseases in people subject to BMT and the serologic response after vaccination. PATIENTS AND METHOD: Study population was people subject to transplantation at least 6 months before initiating vaccination and without immunosuppressive treatment at that time. A prevaccination serologic analysis was carried out, and the hepatitis B, the adult tetanus-diphtheria (Td), the IPV, the influenza and the pneumococccal vaccines were administered in accordance with standard guidelines Depending on the immune status of the patient according to the serologic analysis, the MMR vaccine was administered no sooner than 18 months after transplantation. After vaccination, a serologic analysis was carried out to determine the response. RESULTS: The mean time SD between transplant and the initiation of vaccination was 3.2 2.9 years. Of the 122 recipients of BMT (average age 35.8 13 years; 54.2% male), 51.7% received an allogenic and 48.3% an autologous transplant. Before vaccination, the susceptibility was 48.2% for tetanus, 66.7% for diphtheria, 74.1% for pertussis, 85.9% for hepatitis B, 13.4% for measles, 36.7% for rubella and 9.2% for mumps. The rates of seroconversion with protective titers after vaccination for tetanus, diphtheria and hepatitis B were 94%, 67% and 75% respectively. The response to the MMR vaccine was greater than 70%, with a second dose of the vaccine being needed in 26% of patients. CONCLUSIONS: Susceptibility to vaccine-preventable diseases in transplanted patients is high. The acceptable response to vaccination justifies the development of specific programs. Given the special characteristics of this group of patients, vaccination programs must be simple and flexible.