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Plan now for decisions on which vaccines should go to whom, when and how often.

Flu remains a major killer because of imperfect vaccines and widespread resistance to existing antivirals—problems particularly acute during a pandemic. New findings at the bedside and at the bench could lead to improvements on both fronts. Grace Chen and Kanta Subbarao discuss the implications of research identifying human antibodies than can neutralize a range of viral subtypes. The findings may help lead to a 'universal' vaccine against these diverse and rapidly evolving viruses. Estanislao Nistal-Villán and Adolfo García-Sastre examine two recent studies that reveal the crystal structure of a promising viral drug target, the unique endonuclease domain of the viral polymerase. The findings open the door to the rational design of new influenza virus inhibitors.

Efficient airborne transmission of influenza viruses between humans is associated with use of α2,6-linked sialic acids, not α2,3-linked sialic acids; however, using a loss-of-function approach in which a 2009 pandemic H1N1 influenza virus was engineered to bind α2,3 sialic acids, this study shows in ferrets that the soft palate is an important site for the switch of receptor usage to take place, and reveals that this tissue rapidly selects for transmissible influenza virus with human receptor preference.

Influenza viruses can cause a broad spectrum of disease severity, including devastating cases in some people. Several factors influence the epidemiological success of the virus; the mechanisms of transmission and the strategies for prevention and treatment have an impact on the disease outcome and the incidence of flu infection in the population. Understanding how and why the viruses spread so efficiently among people and determining possible ways to harness this transmission have been arduous tasks, given the limitations of flu animal models. In 'Bedside to Bench', Kanta Subbarao and Seema S. Lakdawala peruse a study that used a human challenge model to assess influenza transmission; this experimental approach shows how transmission can be studied in humans and emphasizes factors that are different compared to animals, such as distinct disease severity and incidence. Lessons can be taken to optimize animal studies. Another issue that dictates the severity of flu episodes is the potential emergence of drug-resistant strains in treated individuals. In 'Bench to Bedside', Anne Kelso and Aeron C. Hurt discuss another concern—the presence of drug-resistant viruses with additional permissive mutations that make them fit to infect and compete with wild-type strains. The fact that these strains can be found in untreated people and can spread poses a public health concern and a challenge for scientists to find new drugs and assess antiviral combinations.

Engineering influenza viruses to study human adaptation is a controversial area of research, with opinions diverging over the wisdom of publishing the full results of such studies.

The pandemic threat posed by avian influenza viruses highlights the need for new safe and efficient vaccines. However, several unique obstacles are faced by researchers in the development of these vaccines against avian influenza viruses. What are these obstacles and how can we overcome them?

Influenza B virus causes substantial illness globally, particularly in children. Treatment options are limited, as the most widely used antiviral drug appears to be less effective than against influenza A. A new antibody targeting the influenza B neuraminidase shows promise in mice as a therapeutic option.

An influenza vaccine is created by attenuating the live virus through targeted proteolysis.

Vaccines against different SARS-CoV-2 variants have been approved, but continued surveillance is needed to determine when the antigen composition of vaccines should be updated, together with clinical studies to assess vaccine efficacy.

High-throughput RNAi screens in human cells suggest new approaches to curb influenza virus infection.

Distinct roadblocks prevent translating basic findings in viral pathogenesis into therapies and implementing potential solutions in the clinic. An ongoing partnership between the Volkswagen Foundation and Nature Medicine resulted in an interactive meeting in 2012, as part of the “Herrenhausen Symposia” series. Current challenges for various fields of viral research were recognized and discussed with a goal in mind—to identify solutions and propose an agenda to address the translational barriers. Here, some of the researchers who participated at the meeting provide a concise outlook at the most pressing unmet research and clinical needs, identifying these key obstacles is a necessary step towards the prevention and cure of human viral diseases.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

Current vaccine strategies for SARS-CoV-2 focus on eliciting neutralising antibodies to the spike protein (S), but differences in immunogenicity of full-length S versus receptor binding domain (RBD) only aren’t fully understood. Here, the authors show immunogenicity of different prime-boost strategies with S and/or RBD in mice and macaques.

Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.

Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.

Chen, Neil, Tan, Rudraraju et al. use an induced trophoblast stem-cell-based model of SARS-CoV-2 infection and identify syncytiotrophoblasts as the cells targeted by the virus in the early placenta.

Proximal nephron in pluripotent stem cell derived kidney organoids are immature with limited support for functional solute channels. Vanslambrouck et al report improved metanephric specification, generating enhanced kidney organoids with superior proximal tubules, spatially arranged nephrons, and applications for disease research, and drug screening.

Unmet need exists for a vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV). Here the authors report the establishment and evaluation, in mice and primates, of a series of MERS-CoV immunogens and show that they can serve as promising leads for vaccine development.

Neutralizing antibody titers elicited by either ancestral or bivalent COVID-19 vaccine boosters are predicted to increase protection against severe disease due to SARS-CoV-2 variants.

In a cohort of recovered patients with COVID-19, virus spike-specific antibodies were consistently elicited, but neutralizing activity was highly variable and inversely correlated with the proportion of CCR6⁺CXCR3⁻ spike-specific circulating follicular helper T cells.

Following the onset of the COVID-19 pandemic in 2020, the number of influenza viruses circulating globally fell to historically low numbers. Although influenza A and B/Victoria lineage viruses returned to normal patterns by 2022, B/Yamagata-lineage viruses have not been identified since 2020. The implications of the apparent extinction of this lineage of viruses on vaccine composition, and the risk of their re-introduction into the human population are discussed.

Identifying molecular predictors of effective vaccination is an important clinical and technical goal. Pulendran and colleagues use a systems biology approach to study human responses to vaccination against influenza and determine the correlates of immunogenicity.

Avian influenza A H7N9 viruses that emerged in China in 2013 have reappeared each year, causing more than 1 600 severe human infections. As these viruses have evolved in nature, they have gained some and can gain additional virulence determinants that enhance their risk for humans, underlining the urgent need to control and eradicate H7N9 viruses in China.

Are you new to virus research and trying to interpret the ever-expanding literature on immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)? Here, the authors compare the different assays and animal models used to measure immunity to SARS-CoV-2 infection and reconcile differences in apparent potency of antibodies assessed in different assays.

Wurzel et al. describe the kinetics of the immune response in relation to clinical and virological features in a 5-month old infant with congenital heart disease and severe COVID-19. The immune response was characterised by an elevated inflammatory response in the acute phase of infection, followed by Th2 skewing and prolonged T cell activation.