Table 1 Summary of immunogen design strategies and progress in evaluation

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]