Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4–45.1] vs 64.9 [57.5–71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18–0.52 vs 0.48–0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.
Several vaccines have been widely used to counteract the global pandemic caused by SARS-CoV-2. However, due to the rapid emergence of SARS-CoV-2 variants of concern (VOCs), further development of vaccines that confer broad and longer-lasting protection against emerging VOCs are needed. Here, we report the immunological characteristics of a self-amplifying RNA (saRNA) vaccine expressing the SARS-CoV-2 Spike (S) receptor binding domain (RBD), which is membrane-anchored by fusing with an N-terminal signal sequence and a C-terminal transmembrane domain (RBD-TM). Immunization with saRNA RBD-TM delivered in lipid nanoparticles (LNP) efficiently induces T-cell and B-cell responses in non-human primates (NHPs). In addition, immunized hamsters and NHPs are protected against SARS-CoV-2 challenge. Importantly, RBD-specific antibodies against VOCs are maintained for at least 12 months in NHPs. These findings suggest that this saRNA platform expressing RBD-TM will be a useful vaccine candidate inducing durable immunity against emerging SARS-CoV-2 strains.
Past SARS-CoV-2 infection is an important determinant of protection from reinfection and of postvaccine immune responses. Our results show that different immunoassays, by design, harbor variable capability of tracking SARS-CoV-2 infection under waning antibody concentrations.
Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable.
16 February 2022 in Journal of Clinical Microbiology
Background: Adults infected withPlasmodiumspp. in endemic areas need to be re-evaluated in light of global malaria elimination goals. They potentially undermine malaria interventions but remain an overlooked aspect of public health strategies.Methods: This study aimed to estimate the prevalence ofPlasmodiumspp. infections, to identify underlying parasite species, and to assess predicting factors among adults residing in an endemic area from the Democratic Republic of Congo (DRC). A community-based cross-sectional survey in subjects aged 18 years and above was therefore carried out. Study participants were interviewed using a standard questionnaire and tested forPlasmodiumspp. using a rapid diagnostic test and a nested polymerase chain reaction assay. Logistic regression models were fitted to assess the effect of potential predictive factors for infections with differentPlasmodiumspp.Results: Overall, 420 adults with an estimated prevalence ofPlasmodiumspp. infections of 60.2% [95% CI 55.5; 64.8] were included. Non-falciparumspecies infected 26.2% [95% CI 22.2; 30.5] of the study population. Among infected participants, three parasite species were identified, includingPlasmodium falciparum(88.5%),Plasmodium malariae(39.9%), andPlasmodium ovale(7.5%) but noPlasmodium vivax. Mixed species accounted for 42.3% of infections while single-species infections predominated withP. falciparum(56.5%) among infected participants. All infected participants were asymptomatic at the time of the survey. Adults belonging to the “most economically disadvantaged” households had increased risks of infections with anyPlasmodiumspp. (adjusted odds ratio, aOR = 2.87 [95% CI 1.66, 20.07]; p < 0.001), compared to those from the "less economically disadvantaged” households. Conversely, each 1 year increase in age reduced the risk of infections with anyPlasmodiumspp. (aOR = 0.99 [95% CI 0.97, 0.99]; p = 0.048). Specifically for non-falciparumspp., males had increased risks of infection than females (aOR = 1.83 [95% CI 1.13, 2.96]; p = 0.014).Conclusion: Adults infected with malaria constitute a potentially important latent reservoir for the transmission of the disease in the study setting. They should specifically be taken into account in public health measures and translational research.