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Table 1 Summary of immunogen design strategies and progress in evaluation

From: HIV-1 vaccine immunogen design strategies

Design strategy Expected outcome In vitro evaluation Animal trials Human trials Key ref.
1. Mimicking native trimer: remove non-functional Env from VLP bNAb Recognised by NAb but not non-NAb - - [29,31]
2. Mimicking native trimer: soluble SOSIP-modified Env trimer bNAb Recognised by bNAb but not non-NAb Resembles Env trimer by electron microscopy - - [39]
3. Stabilised bNAb epitope: epitope-scaffolds bNAb Bound to bNAb Ones tested did not elicit NAb - [33,46,47]
4. Stabilised bNAb epitope: targeting germline and driving maturation bNAb Potently activated germline and mature VRC01 B cells - - [49]
5. Stabilised bNAb epitope: fragment immunogen bNAb Ab induced in rabbits neutralised tier I, II and III viruses Induced b12 bNAb in rabbits - [51]
6. Mosaic immunogens T cell responses to diverse strains, reduce escape Processed and expressed by human T cells Increased breadth and depth of T cell responses Reduced per exposure probability of infection by ≈ 90% - [67,70-72]
7. Conserved element immunogens T cell responses to diverse strains, reduce escape/attenuate virus T cell responses elicited in humans inhibited viruses Highly immunogenic High magnitude and breadth of T cell responses in 100% vaccinees [21,81]
8. Escape-cornering immunogens (computational model) Reduce escape/attenuate virus Fitness testing of mutants supported model predictions - - [84,86]
9. Immunogens using CMV vectors Persistent T cell responses to act early - 50% monkeys clear SIV infection early Persistent, unusually broad T cell responses - [55,91,92]
  1. ref – references; VLP – virus-like particles; bNAb – broadly neutralising antibodies; NAb – neutralising antibodies; SOSIP - disulphide bond between gp120 and gp41 and gp41 trimer stabilising mutation I559P; Env – envelope; CMV – cytomegalovirus; SIV – simian immunodeficiency virus.