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Optimizing HIV preventive therapy administration is key to improved uptake in vulnerable populations. Here, the authors report that subcutaneous administration of broadly neutralizing antibodies formulated with EDP is safe while reducing infusion duration and number of injections in healthy female participants.

Gold-standard evidence for correlates of protection is provided by analysis of a randomized phase 3 trial of Ad26.COV2.S for protection against moderate to severe-critical COVID-19 disease.

Authors have previously reported on the efficacy and safety of the recombinant spike protein nanoparticle vaccine, NVX-CoV2373, in healthy adults. In this work, they assess anti-spike binding IgG, anti-RBD binding IgG and neutralising antibody titer as correlates of risk and protection against COVID-19.

In this work, the authors study the immunological and virological effects of administering either wild-type anti-HIV-1 broadly neutralizing antibodies (bNAbs) or bNAbs with a mutation that increases binding to Fc-gamma receptors (FcγRs) to rhesus macaques in the acute phase of SHIV_AD8-EO infection.

Viral sequencing reveals subclinical infections in animals challenged with simian immunodeficiency virus even in the presence of potent neutralizing antibodies, with implications for clinical trials of antiviral agents against human immunodeficiency virus.

In this study, the authors report that post-vaccination neutralizing and binding antibody levels in the ENSEMBLE trial associate with Ad26.COV2.S vaccine efficacy (VE) against severe-critical COVID-19, with substantial VE even at unquantifiable neutralizing antibody titer.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

In a first-in-human trial of a triple combination of broadly neutralizing antibodies in people living with HIV, 83% of participants maintained virologic suppression for the duration of antibody therapy, with 42% showing virologic suppression for at least 38–44 weeks, despite the decline of serum antibody concentrations to low or undetectable levels.

Using data from a phase 3 efficacy trial, the authors here show that post-boost Omicron BA.1 spike-specific binding and neutralizing antibodies inversely correlate with Omicron COVID-19 and booster efficacy for naive and non-naive participants, supporting the continued use of antibody as a surrogate endpoint.

First-in-human trial of a self-assembling, ferritin nanoparticle-based influenza vaccine shows evidence that this new platform can elicit neutralizing and cross-reactive antibodies and has potential for further vaccine development.

Vaccines against the WA1 SARS-CoV2 strain confer protection against other variants. However, the mechanisms underlying cross-protection are not fully understood. Here, the authors develop a method for rapid analysis of single B cells from patient samples and show that infection with a variant elicits convergent, public B cell responses to other variants.

An mRNA vaccine platform to prevent HIV-1 infection generated broadly neutralizing antibodies in non-human primates and protected some animals from infection, raising hope that optimization of this approach might lead to an effective HIV vaccine.

Small molecule drugs can affect clearance of monoclonal antibodies, but this hasn’t been assessed for oral HIV-1 pre-exposure prophylaxis. Here, the authors find that faster serum clearance of an experimental IgG1 monoclonal antibody, VRC01, is associated with use of tenofovir-emtricitabine, possibly explained by increased epithelial intestinal permeability.

Vaccines that protect nonhuman primates from lethal Ebola virus infection have been developed, but their protective mechanisms have not been clearly delineated. Nancy Sullivan et al. now report that the protective efficacy of a recombinant Ad5-based Ebola virus vaccine relies primarily on CD8⁺ T cells rather than on antibodies. The findings suggest that clinical development of T cell–based vaccines against Ebola virus is warranted.

Understanding the mechanistic basis of vaccine efficacy is crucial to the development of next-generation vaccines. Sekaly and colleagues find that activation of the transcription factor CREB1 by the RV144 HIV-1 vaccine underpins the induction of robust adaptive immunity.

Bivalent vaccines elicit broad immune responses that neutralize ancestral SARS-CoV-2 and variants of concern and offer a customizable approach to protect from COVID-19 as new virus variants emerge.

Distinct monocyte subsets associate with different outcomes of SIV vaccines.

The persistence of latently infected T cells is a major hurdle to eradication of HIV by antiviral therapy. It now seems that HIV latency can occur during normal T-cell differentiation in the thymus, and is regulated by the overall state of cellular gene transcription (pages 459–464).

Here, the authors apply positron emission tomography (PET) imaging to visualize HIV tissue-wide burden in infected individuals using a radiolabeled broadly neutralizing antibody, ⁸⁹Zr-VRC01, and show that PET tracer lymph node uptake positively correlates with HIV protein levels measured directly from cells obtained from these tissues. This strategy may allow non-invasive characterization of residual HIV infection in the setting of therapeutic interventions.

Innate immune responses to mRNA vaccines are less well understood than adaptive immunity. Here, the authors comprehensively characterize the innate and adaptive immune responses to mRNA-1273 vaccinations in rhesus macaques and show how the vaccine activates interactions among components of the two systems.

The lack of natural immunity against HIV has been a major hindrance to the search for immune correlates of protection. Here, the authors propose a new approach for clinical trials of HIV vaccine efficacy that should help to increase our chances of identifying immune correlates of protection.

The RV144 vaccine trial showed reduced risk of HIV-1 acquisition, but mechanisms underlying protection are poorly understood. Here, Fourati et al. assess the transcriptomic profile of blood collected from 223 vaccinees and 40 placebo recipients and identify IRF7 as a mediator of protection.

A combination of three monoclonal antibodies transiently reduced viremia in people living with HIV-1 and not on antiretroviral therapy, but it did not prevent viral rebound. Further studies are needed to determine if this approach can be optimized.

One of the main hurdles to curing HIV infection are viral reservoirs. Here, the authors develop a trispecific antibody and demonstrate its ability to simultaneously activate and target latently HIV−1 infected cells for elimination by T cells as an alternative strategy for HIV cure.

The elimination of latently infected cells is a sought after goal in the treatment of HIV-1 infections. Here the authors develop an approach to eliminate latently HIV-1 infected cells by using an immunomodulatory protein, which can activate viral gene expression in these cells and direct T lymphocytes to lyse them in vitro.

Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

The analysis of multiple SIV vaccine regimens in macaques leads to the identification of a key two-amino-acid signature that confers resistance to neutralizing antibodies; a similar mechanism of immune escape is shown to operate in HIV and may explain the limited efficacy seen in HIV vaccine trials.

HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.

Vaccari et al. report that SIV vaccines formulated with two different adjuvants elicit distinct immune responses and effects on SIV acquisition in rhesus macaques.

The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.

HIV-1 causes CD4⁺T-cell death through viral integration by stimulation of DNA-dependent protein kinase (DNA-PK), a protein known to act in the p53 damage response pathway for double-stranded DNA breaks, in activated cells.