RESUMO
Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31-60 (n = 110) and 61-90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.
Assuntos
Vacinas contra COVID-19 , COVID-19/imunologia , COVID-19/prevenção & controle , Imunidade Humoral , SARS-CoV-2 , Vacina de mRNA-1273 contra 2019-nCoV , Centros Médicos Acadêmicos , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Vacina BNT162 , California/epidemiologia , Serviços Médicos de Emergência , Socorristas , Pessoal de Saúde , Humanos , Imunoensaio , RNA Mensageiro/metabolismo , UniversidadesRESUMO
Current HIV vaccines in development appear unlikely to prevent infection, but could provide benefits by increasing survival; such vaccines are described as disease-modifying vaccines. We review the current status of vaccines and modeling vaccines. We also predict the impact that disease-modifying vaccines could have in South Africa, where multiple subtypes are co-circulating. We model transmissibility/fitness differences among subtypes. We used uncertainty analyses to model vaccines with four characteristics: (i) take, (ii) duration of immunity, (iii) reduction in transmissibility/fitness, and (iv) increase in survival. We reconstructed, and forecasted, the South African epidemic from 1940 to 2140 (assuming no vaccination). We predict that: (i) incidence will peak in 2014, decline, and stabilize, (ii) prevalence will continue to rise, and (iii) the AIDS death rate curve will peak in 2022. Our predictions show that (over the next 135 years) the epidemic in South Africa will switch from a predominantly Subtype C epidemic to an epidemic driven by other subtypes. We predict that the epidemic could remain unchanged, even with mass vaccination with a vaccine that is equally effective against all co-circulating subtypes. However, if the non-C subtypes are less (or equally) transmissible as Subtype C then disease-modifying vaccines could result in eradication. Thus, in countries where multiple-subtypes are co-circulating it is critical to realize that small biological differences among subtypes will have dramatic consequences for the effectiveness of HIV vaccination campaigns. A slight difference in fitness will determine whether a disease-modifying vaccine has almost no impact on the epidemic or can achieve eradication.
Assuntos
Vacinas contra a AIDS/imunologia , Infecções por HIV/prevenção & controle , Saúde Pública , Infecções por HIV/epidemiologia , Política de Saúde , Humanos , África do Sul/epidemiologiaRESUMO
Macrophages and CD4(+) lymphocytes are the principal target cells for human immunodeficiency virus type 1 (HIV-1) infection, but the molecular details of infection may differ between these cell types. During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63. Pretreatment of primary macrophages with anti-CD63 MAb, but not MAbs to other macrophage cell surface tetraspanins (CD9, CD81, and CD82), was shown to inhibit infection by several R5 and dualtropic strains, but not by X4 isolates. The block to productive infection was postfusion, as assessed by macrophage cell-cell fusion assays, but was prior to reverse transcription, as determined by quantitative PCR assay for new viral DNA formation. The inhibitory effects of anti-CD63 in primary macrophages could not be explained by changes in the levels of CD4, CCR5, or beta-chemokines. Infections of peripheral blood lymphocytes and certain cell lines were unaffected by treatment with anti-CD63, suggesting that the role of CD63 in HIV-1 infection may be specific for macrophages.