Mucosal vaccines — fortifying the frontiers

Abstract

The global burden of mortality and morbidity associated with infectious diseases caused by mucosal pathogens remains unacceptably high. Indeed, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic provides a brutal reminder of the continual threat of novel mucosal infectious challenges, in addition to the threat posed by many widespread mucosal infections for which no or only suboptimal vaccines exist. Now more than ever, there is a clear focus on vaccine requirements for respiratory pathogens but, importantly, new and improved vaccines are also urgently needed for numerous enteric pathogens and other agents such as those causing sexually transmitted diseases (STDs) and oncogenic viruses that gain access through the mucosae.Respiratory pathogens remain a prominent cause of global mortality, with lower respiratory tract infections constituting the fourth leading cause of death worldwide 1 . Lower respiratory tract infections are responsible for approximately 2.4 million deaths per annum, with Streptococcus pneumoniae, respiratory syncytial virus (RSV), Haemophilus influenzae B and influenza virus taking a particularly high toll on the young (<5 years old) and older people 2 . There is currently no approved vaccine for RSV infection, which is particularly prevalent in children and infants [2][3][4] , and although there are licensed vaccines targeting respiratory pathogens such as Mycobacterium tuberculosis, S. pneumoniae, Bordetella pertussis and influenza virus, improved vaccines for these pathogens are required to enhance suboptimal protection, particularly at the site of infection, and to increase coverage (Fig. 1). There are indications that innovative mucosal vaccine approaches offer promise for these infections. For example, live attenuated influenza vaccines given intranasally are now an integral part of influenza vaccination strategies with particular application to children 5,6 , intranasally administered B. pertussis vaccines have entered phase II trials 7,8 (Supplementary Table 1) following successful phase I completion, and preclinical data investigating the intranasal delivery of Bacillus Calmette-Guérin for M. tuberculosis have yielded promising results 9 . The emergence of SARS-CoV-2 has firmly demonstrated how deadly and disruptive respiratory pathogens can be, with approximately 2.6 million deaths attributed to this pathogen at the time of writing 10 and estimates that the SARS-CoV-2 pandemic will continue to stunt global economic growth in 2021, particularly in low-income countries 11 . Although an array of effective SARS-CoV-2 vaccines have been designed and implemented, challenges in mass production and deployment

Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

“…VE was also higher in individuals aged 18-34 years than in individuals aged 35-64 years for both ChAdOx1 and BNT162b2 (heterogeneity P = 0.002 and P = 0.001, respectively). However, there was no evidence of differences between individuals reporting versus not reporting long-term health conditions or between <6 versus ≥6 weeks (median (IQR) 25 (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34) versus 72 (63-77) d) between the first and second BNT162b2 vaccination (heterogeneity P = 0.18; Supplementary Table 6).…”

“…One explanation could be differential effects of vaccination on mucosal and systemic immunity 20 . In theory, the former is more important for preventing carriage, transmission and infection becoming established, whereas the latter is more important for preventing severe disease once infected 21 . Studies in rhesus macaques showed greater reductions in SARS-CoV-2 viral load in the lungs and prevention of pneumonia, without reducing viral loads in the upper respiratory tract with intramuscular ChAdOx1 (ref.…”

Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

“…One explanation could be differential effects of vaccination on mucosal and systemic immunity 25 . In theory, the former is more important for preventing carriage, transmission, and infection becoming established, while the latter is more important for preventing severe disease once infected 26 . Studies in rhesus macaques showed greater reductions in SARS-CoV-2 viral load in the lungs and prevention of pneumonia, without reducing viral loads in the upper respiratory tract with intramuscular ChAdOx1 27 , and protection against viral replication at much lower concentrations in the lower than the upper respiratory tract with intramuscular mRNA-1273 28 .…”

High Resolution Single Cell Maps Reveals Distinct Cell Organization and Function Across Different Regions of the Human Intestine

“…Moreover, aberrations in cellular density have been associated with disease states such as inflammatory bowel disease (IBD). As the intestine is the largest immune organ in the body 14 , evaluating immune cell localization and cellular interactions in the gut is critical for understanding oral vaccine design 15 , interactions regulating the gut microbiota 16 , regulation of allergic food responses 17 , axes critical for wound repair 18 , and immune system responses and immunotherapies for cancer [19][20][21][22] .…”