Booster Vaccination Against SARS-CoV-2 Induces Potent Immune Responses in People With Human Immunodeficiency Virus.

BACKGROUND: People with human immunodeficiency virus (HIV) on antiretroviral therapy (ART) with good CD4 T-cell counts make effective immune responses following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed 12 months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µL. Immune responses to the ancestral strain and variants of concern were measured by anti-spike immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, activation induced marker (AIM) assay, and T-cell proliferation. FINDINGS: In total, 54 participants received 2 doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) 1 year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titers (MSD), ACE-2 inhibition, and IgG ELISA results were significantly higher compared to Day 182 titers (P < .0001 for all 3). SARS-CoV-2 specific CD4+ T-cell responses measured by AIM against SARS-CoV-2 S1 and S2 peptide pools were significantly increased after a third vaccine compared to 6 months after a first dose, with significant increases in proliferative CD4+ and CD8+ T-cell responses to SARS-CoV-2 S1 and S2 after boosting. Responses to Alpha, Beta, Gamma, and Delta variants were boosted, although to a lesser extent for Omicron. CONCLUSIONS: In PWH receiving a third vaccine dose, there were significant increases in B- and T-cell immunity, including to known variants of concern (VOCs).

Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial.

BACKGROUND: Rabies kills around 60 000 people each year. ChAdOx2 RabG, a simian adenovirus-vectored rabies vaccine candidate, might have potential to provide low-cost single-dose pre-exposure rabies prophylaxis. This first-in-human study aimed to evaluate its safety and immunogenicity in healthy adults. METHODS: We did a single-centre phase 1 study of ChAdOx2 RabG, administered as a single intramuscular dose, with non-randomised open-label dose escalation at the Centre for Clinical Vaccinology and Tropical Medicine, Oxford, UK. Healthy adults were sequentially allocated to groups receiving low (5 × 109 viral particles), middle (2·5 × 1010 viral particles), and high doses (5 x 1010 viral particles) of ChAdOx2 RabG and were followed up to day 56 after vaccination. The primary objective was to assess safety. The secondary objective was to assess immunogenicity with the internationally standardised rabies virus neutralising antibody assay. In an optional follow-up phase 1 year after enrolment, we measured antibody maintenance then administered a licensed rabies vaccine (to simulate post-exposure prophylaxis) and measured recall responses. The trial is registered with ClinicalTrials.gov, NCT04162600, and is now closed to new participants. FINDINGS: Between Jan 2 and Oct 28, 2020, 12 adults received low (n=3), middle (n=3), and high doses (n=6) of ChAdOx2 RabG. Participants reported predominantly mild-to-moderate reactogenicity. There were no serious adverse events. Virus neutralising antibody concentrations exceeded the recognised correlate of protection (0·5 IU/mL) in three middle-dose recipients and six high-dose recipients within 56 days of vaccination (median 18·0 IU/mL). The median peak virus neutralising antibody concentrations within 56 days were 0·7 IU/mL (range 0·0-54·0 IU/mL) for the low-dose group, 18·0 IU/mL (0·7-18·0 IU/mL) for the middle-dose group, and 18·0 IU/mL (6·0-486·0 IU/mL) for the high-dose group. Nine participants returned for the additional follow-up after 1 year. Of these nine participants, virus neutralising antibody titres of more than 0·5 IU/mL were maintained in six of seven who had received middle-dose or high-dose ChAdOx2 RabG. Within 7 days of administration of the first dose of a licensed rabies vaccine, nine participants had virus neutralising antibody titres of more than 0·5 IU/mL. INTERPRETATION: In this study, ChAdOx2 RabG showed an acceptable safety and tolerability profile and encouraging immunogenicity, supporting further clinical evaluation. FUNDING: UK Medical Research Council and Engineering and Physical Sciences Research Council.

Influence of polyploidy on insect herbivores of native and invasive genotypes of Solidago gigantea (Asteraceae).

Herbivores are sensitive to the genetic structure of plant populations, as genetics underlies plant phenotype and host quality. Polyploidy is a widespread feature of angiosperm genomes, yet few studies have examined how polyploidy influences herbivores. Introduction to new ranges, with consequent changes in selective regimes, can lead to evolution of changes in plant defensive characteristics and also affect herbivores. Here, we examine how insect herbivores respond to polyploidy in Solidago gigantea, using plants derived from both the native range (USA) and introduced range (Europe). S. gigantea has 3 cytotypes in the US, with 2 of these present in Europe. We performed bioassays with generalist (Spodoptera exigua) and specialist (Trirhabda virgata) leaf-feeding insects. Insects were reared on detached leaves (Spodoptera) or potted host plants (Trirhabda) and mortality and mass were measured. Trirhabda larvae showed little variation in survival or pupal mass attributable to either cytotype or plant origin. Spodoptera larvae were more sensitive to both cytotype and plant origin: they grew best on European tetraploids and poorly on US diploids (high mortality) and US tetraploids (low larval mass). These results show that both cytotype and plant origin influence insect herbivores, but that generalist and specialist insects may respond differently.

Effects of polyploidy on secondary chemistry, physiology, and performance of native and invasive genotypes of Solidago gigantea (Asteraceae).

The role of polyploidy in facilitating invasiveness of introduced plants has not been well explored. Examination of traits of diploid and polyploid plants in both their native and introduced ranges can shed light on evolutionary processes occurring postintroduction in invasive plants. We determined the distribution and prevalence of cytotypes of Solidago gigantea in both its native range (USA) and introduced range (Europe), and measured a suite of biochemical, physiological, and reproductive characters for plants from both continents. Tetraploids were the most frequent cytotype encountered on both continents, while hexaploids were found only in the USA. Hexaploids were the most distinctive cytotype, with fewer differences observed between diploids and tetraploids. Comparison of diploids and tetraploids in the USA and Europe showed that traits changed in concert for both cytotypes. Both diploids and tetraploids in Europe had reduced concentrations of three classes of secondary chemical and invested relatively more into rhizomes than into flowers. The same changes occurring in both cytotypes in the introduced range show that altered phenotypes of European plants are not due to shifts in the proportions of cytotypes but instead occur within them. There was no evidence that polyploids evolve more quickly in the introduced range.