HIV vaccines in 2022: where to from here?

The way forward requires all stakeholders—funders, researchers, product developers, trial networks and advocates—to analyse closely what the field has learned to date, develop clarity on the critical scientific challenges and agree on a coordinated strategy to pursue answers. Since early 2020, two trials of different HIV vaccine candidates and two trials testing antibody-mediated prevention (with implications for vaccines) showed no overall efficacy in preventing HIV acquisition. The AMP trials confirmed that a broadly neutralizing antibody (bnAb) can offer efficacy, when the circulating variants of HIV are highly sensitive to the bnAb neutralization. Because only a minority of circulating strains associated with incident HIV infection were neutralized by the single VRC01 bnAb, these studies suggest that a combination of bnAbs is needed to achieve broad protection. While almost four decades of research have yet to deliver a licensed HIV vaccine, they have been an engine of discovery, providing vaccine know-how, technology, clinical trial network and site infrastructure, researchers and advocates that galvanized the development of multiple COVID-19 vaccines in record time.

SARS-COV-2 Vaccine Responses in Renal Patient Populations (preprint)

BackgroundDialysis patients and immunosuppressed renal patients are at increased risk of COVID-19 and were excluded from vaccine trials. We conducted a prospective multicentre study to assess SARS-CoV-2 vaccine antibody responses in dialysis patients and renal transplant recipients, and patients receiving immunosuppression for autoimmune disease. Methods Patients were recruited from three UK centres (ethics:20/EM/0180) and compared to healthy controls (ethics:17/EE/0025). SARS-CoV-2 IgG antibodies to spike protein were measured using a multiplex Luminex assay, after first and second doses of Pfizer BioNTech BNT162b2(Pfizer) or Oxford-AstraZeneca ChAdOx1nCoV-19(AZ) vaccine.Results692 patients were included (260 dialysis, 209 transplant, 223 autoimmune disease (prior rituximab 128(57%)) and 144 healthy controls. 299(43%) patients received Pfizer vaccine and 379(55%) received AZ.  Following two vaccine doses, positive responses occurred in 96% dialysis, 52% transplant, 70% autoimmune patients and 100% of healthy controls. In dialysis patients, higher antibody responses were observed with the Pfizer vaccination. Predictors of poor antibody response were triple immunosuppression (adjusted odds ratio [aOR]0.016;95%CI0.002-0.13;p<0.001) and mycophenolate mofetil (MMF) (aOR0.2;95%CI 0.1-0.42;p<0.001) in transplant patients; rituximab within 12 months in autoimmune patients (aOR0.29;95%CI 0.008–0.096;p<0.001) and patients receiving immunosuppression with eGFR 15-29ml/min (aOR0.031;95%CI 0.11–0.84;p=0.021). ConclusionsAmongst dialysis, kidney transplant and autoimmune populations SARS-CoV-2 vaccine antibody responses are reduced compared to healthy controls. A reduced response to vaccination was associated with rituximab, MMF, triple immunosuppression CKD stage 4. Vaccine responses increased after the second dose, suggesting low-responder groups should be prioritised for repeated vaccination. Greater antibody responses were observed with the mRNA Pfizer vaccine compared to adenovirus AZ vaccine in dialysis patients suggesting that Pfizer SARS-CoV-2 vaccine should be the preferred vaccine choice in this sub-group.

Lasting changes to circulating leukocytes in people with mild SARS-CoV-2 infections (preprint)

Survivors of severe SARS-CoV-2 infections frequently suffer from a range of post-infection sequelae. Whether survivors of mild or asymptomatic infections can expect any long-term health consequences is not yet known. Herein we investigated lasting changes to soluble inflammatory factors and cellular immune phenotype and function in individuals who had recovered from mild SARS-CoV-2 infections (n=22) compared to those that had recovered from other mild respiratory infections (n=11). Individuals who had mild SARS-CoV-2 infections had elevated levels of C-reactive protein 1-3 months after symptom onset, and changes in phenotype and function of circulating T cells that were not apparent in individuals 6-9 months post-symptom onset. Markers of monocyte activation and expression of adherence and chemokine receptors indicative of altered migratory capacity were also higher at 1-3 months post-infection in individuals who had mild SARS-CoV-2, but these were no longer elevated by 6-9 months post-infection. Perhaps most surprisingly, polyclonal activation of T cells was higher in individuals who had recently experienced a mild SARS-CoV-2 infection compared to individuals with other recent respiratory infections. These data are indicative of prolonged immune activation and systemic inflammation that persists for up to three months after mild or asymptomatic SARS-CoV-2 infections.