Synthetic oligodeoxynucleotides (ODNs) containing cytosine-guanosine (CpG) motifs stimulate B and plasmacytoid dendritic cells of the vertebrate immune system. We found that in primates strong stimulation of these cells could also be achieved using certain non-CpG ODNs. The immunostimulatory motif in this case is a sequence with the general formula PyNTTTTGT in which Py is C or T, and N is A, T, C, or G. Assays performed on purified cells indicated that the immunostimulatory activity is direct. The use of a nuclease-resistant phosphorothioate backbone is not a necessary condition, since phosphodiester PyNTTTTGT ODNs are active. It was also demonstrated that ODN 2006, a widely used immunostimulant of human B cells, possess two kinds of immunostimulatory motifs: one of them mainly composed of two successive TCG trinucleotides located at the 5′ end and another one (duplicated) of the PyNTTTTGT kind here described. Even though PyNTTTTGT ODNs are mainly active on primate cells, some of them, bearing the CATTTTGT motif, have a small effect on cells from other mammals. This suggests that the immunostimulatory mechanism activated by these ODNs was present before, but optimized during, evolution of primates. Significant differences in the frequency of PyNTTTTGT sequences between bacterial and human DNA were not found. Thus, the possibility that PyNTTTTGT ODNs represent a class of pathogen-associated molecular pattern is unlikely. They could, more reasonably, be included within the category of danger signals of cell injury.
Background
Comparing humoral responses in SARS-CoV-2 vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/infection (‘hybrid immunity’), may clarify predictors of vaccine immunogenicity.
Methods
We studied 2660 U.S. Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-IgG responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or sub-clinical SARS-CoV-2 reinfection from all groups.
Results
Multivariable regression results indicated vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (p < 0.01), regardless of prior infection severity. An increased time between infection and vaccination was associated with a greater post-vaccination IgG response (p < 0.01). Vaccination-alone elicited a greater IgG response, but more rapid waning of IgG (p < 0.01), compared to infection-alone (p < 0.01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared to JNJ-78436735 (p < 0.01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (p < 0.01).
Conclusions
Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared to vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.
The diversity of pendulous Usnea species in tropical South America (Bolivia, Brazil, Colombia, Ecuador, Paraguay, Peru and Venezuela) and the Galapagos Islands is discussed with reference to 23 species. Usnea crenulata Truong & Clerc is newly described. Usnea articulata, U. deformis, U. dimorpha, U. geissleriana, U. merrillii, U. perhispidella, U. sanctaeritae, U. subflammea and U. transitoria are newly reported for South America. Modern descriptions are provided for Usnea amabilis, U. arthroclada, U. dodgei, U. humboldtii and U. regia. We propose to reject the synonymy of U. hesperina with U. schadenbergiana, and the valid name for U. hesperina is therefore U. subgracilis. Distinct patterns of unidentified triterpenoids have been detected by thin-layer chromatography and are used to characterize several species within this group. The morphology, branch anatomy, chemistry, ecology and distribution of each species are given, together with an identification key.
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