Rotavirus vaccine efficacy: current status and areas for improvement

Carvalho, Miguel F.; Gill, Davinder

Intranasal vaccination also shows promise provided that vector and adjuvants are properly sourced. 78, 79 The technology is currently approved for live attenuated influenza vaccine. 80 It is therefore possible that this route of administration could be used to circumvent the limitations of oral Rotavirus immunizations. Interestingly, simian and porcine Rotavirus NSP4 have shown adjuvant properties in mice when co-administered with model antigens, increasing both serum IgG and faecal IgA responses. 81 In addition, intranasal (and intramuscular) delivery of recombinant human Rotavirus VP6 combined with Norovirus virus-like particles led to a reduction of at least 65% in Rotavirus shedding in faeces upon Rotavirus challenge in mice. 82 Live cultures of lactic acid bacteria are also used for mucosal vaccine delivery as they are quite resistant to gastric acid but further encapsulation protects surface-displayed antigens from adverse conditions. Also, different strains have distinct adjuvant and adhesive abilities, can persist in the gut for varying amounts of time and can lead to the expression of diverse cytokines. 83 Examples include oral and intranasal delivery of SARS coronavirus spike protein displayed by Lactobacillus casei in mice leading to specific serum IgG as well as intestinal and lung IgA responses with in vitro neutralization activity. 79 Also, Lactococcus lactis expressing HPV16 E7 antigen with or without co-administration of strain expressing IL-12 were used in intranasal immunization of mice. Following lethal challenge with tumour cell line TC-1, 50% of mice treated with E7/IL-12 were tumour-free after 100 days while the remaining mice had significantly smaller tumour sizes (~1 cm 3 ) than controls immunized with L. lactis alone (all of which perished after 35 days; median tumour size~6 cm 3 ). 78 In summary, M cell targeting has received considerable attention for increasing mucosal vaccine efficiency. Although their low numbers can be raised, the risk of adverse reactions led several groups to discover naturally occurring or randomly selected M cell-specific targeting peptides. When tethered to antigens these moieties lead to higher immune responses in mucosa and serum. In addition, encapsulation of antigens in nanoparticles allows for protection of cargo from digestive tract enzymes, mucoadhesion and pH-dependent release at different locations of the gut, such as M cell-enriched ileum. Alternative immunization methods comprise e.g. transgenic plants that may not only allow for vaccine antigen expression and delivery but also long term storage. Also, intradermal, buccal/sublingual and intranasal delivery could offer solutions to overcome the barriers of EE.