Table 1.
Hypothesized advantages and concerns of various prime-boost combinations with the leading dengue vaccines, ordered top to bottom from least to most likely to be immunogenic. Note, Dengvaxia is also called CYD-TDV and is abbreviated here as CYD. TAK-003 is abbreviated here as TAK.
| Vaccine Sequence | Advantages | Concerns |
|---|---|---|
| CYD/CYD/CYD | Decreases hospitalization in dengue immune individuals. | Increased risk of severe dengue in seronegative people. No dengue capsid or non-structural protein antigens. |
| TAK/TAK | Induces broad protection in dengue immune individuals. Protects against DENV1 and DENV2 in seronegative individuals. | Limited DENV3 protection and unknown DENV4 protection in seronegative people. Induced mainly DENV2 type-specific antibodies. Immunity against non-structural proteins is primarily against DENV2 with proportionally less immunity to those of other serotypes. |
| TAK/CYD | TAK will induce immunity against DENV non-structural proteins, especially DENV2. Induce type-specific antibodies against DENV2 and DENV4. | TAK may neutralize CYD, but this could potentially be overcome by increasing vaccine interval. May not broaden T cell response compared to TAK/TAK although heterologous prime did bolster CYD CD8+ T cell responses. |
| CYD/TAK | Induce type-specific antibodies against DENV2 and DENV4. CYD will not neutralize but may enhance TAK, improving immunogenicity. If safe, could be beneficial for those who have received CYD. | Possible effects of original antigenic sin with giving CYD first, although CYD seems to induce cellular response mostly against yellow fever. Yellow fever immunity is associated with increased response to dengue vaccines. |
| TV003/TV003 | Balanced DENV1-4 immunity in phase 1/2 trials in both seronegative and seropositive individuals. | Phase 3 data not available yet. Does not contain DENV2 non-structural proteins. Second vaccine seems to be neutralized by the first and does not bolster immunity. |
| TV003/CYD | Different parent strains and backbones may broaden immunity some. | TV003 could neutralize CYD. |
| CYD/TV003 | CYD may enhance TV003 and prime immune cells, improving immunogenicity. If safe, could be beneficial for those who have received CYD. | Could cause more reactogenicity, although this was not seen in trials of flavivirus immune individuals receiving TV003 vaccine. |
| TV003/TAK | TAK has DENV2 non-structural proteins, which complements TV003 DENV1,3,4 non-structural proteins. Different parent strains. | TV003 could neutralize TAK, although may be less likely than TV003/TV003 given different non-structural proteins and parent strains. |
| TAK/TV003 | May be ideal combination because the vaccine with narrower immune responses is first, complementary T cell antigens. | TAK may enhance TV003 vaccine and increase reactogenicity, although this was not observed in individuals with previous flavivirus exposure who received TV003. |