Search

Combination immunotherapy approaches might be effective in inducing sustained control of HIV by slowing rebound and improving CD8⁺ T cell responses.

There is renewed enthusiasm in developing an HIV vaccine and in understanding the requirements to elicit broadly neutralizing HIV-specific antibodies. In May 2012, a workshop convened researchers to discuss the interplay of CD4⁺ T cell and antibody responses to help identify key questions and areas of research that can inform future vaccine development. This Perspective summarizes the discussion of three main topics on the role of CD4⁺ T cells in HIV vaccine design.

The authors describe the isolation and characterization of broadly cross-neutralizing monoclonal antibodies (mAbs) against diverse H5Nx viruses from individuals who received a monovalent H5N1 vaccine 15 years ago. They identify five mAbs that potently neutralized the majority of H5 clades and protected against lethal 2.3.4.4b H5N1 infection in mice.

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.

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.

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.

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.

Distinct monocyte subsets associate with different outcomes of SIV vaccines.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

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.