Swedish prime-boost HIV DNA vaccine shows strong responses

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A Swedish plasmid DNA HIV vaccine developed with European Union support has stimulated strong immune responses in a small phase 1 trial, Eric Sandstrom of Stockholm’s Karolinska Institute reported on Wednesday at AIDS Vaccine ’06 in Amsterdam.

Plasmid DNA inmunogens are promising candidates for a HIV vaccine due to the profile of the induced immune response, cost and robustness.

However, the immune response is weak when given alone as a standard intramuscular injection. The immune response may be increased in several ways. Intradermal immunisation has, in other systems, given stronger responses that have been further increased by concomitant administration of GM-CSF (granulocyte macrophage colony stimulating factor).

Glossary

recombinant

An organism, cell or genetic material formed by genetic recombination (or reconstruction).

intramuscular

Injected into a muscle.

adjuvant

A substance administered with a vaccine that increases the effectiveness of the vaccine.

attenuated

Weakened. Attenuated viruses are often used as vaccines because they no longer cause disease but may still stimulate a strong immune response.

antigen

Something the immune system can recognise as 'foreign' and attack.

Intramucosal administration might accomplish the same thing and, in addition, prime for systemic as well as mucosal immunity. The response can be further boosted with later administration of the same antigen in a live, non-replicating vector, MVA. This combination has significantly reduced SIV infection in immunised macaques.

The Swedish vaccine uses genes from HIV’s envelope, reverse transcriptase and gag regions derived from subtypes E (env) from Tanzania and A (gag and RT) from Thailand.

The trial recruited 40 healthy HIV-negative volunteers in Sweden and Tanzania who were randomised to four groups:

  • Intradermal injection
  • Intramuscular injection
  • Intradermal injection with recombinant GM-CSF as an adjuvant
  • Intramuscular injection with recombinant GM-CSF as an adjuvant

Participants received three priming injections at months 0, 1 and 3, and were then randomised to receive a booster injection of MVA that incorporated env, gag and pol genes from the subtypes AE recombinant CRF01A_E at month 9, either intradermally or intramuscularly.

ELISPOT testing for T-cell reactivity demonstrated that after booster dosing, 92% showed reactivity to HIV peptide pools (a positive response was classified as >40 spots per 106 peripheral blood mononuclear cells), and 97% of participants showed HIV-specific T-cell proliferative responses.

Eric Sandstrom said that the preliminary study showed that the vaccine was highly immunogenic despite common exposure to smallpox vaccinations in the volunteer group (the MVA boosting vector is an attenuated form of pox virus), and there were no adverse reactions to the booster dose. Influenza-like symptoms were seen in the GM-CSF arms of the study.

References

Sandstrom E et al. Multigene, multiclade HIV-1 plasmid DNA prime and MVA boost is safe and highly immunogenic in healthy human volunteers. AIDS Vaccine 06, Amsterdam, abstract A03-02, 2006.