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Accelerated heterologous adenovirus prime-boost SIV vaccine in neonatal rhesus monkeys
Jinyan Liu1, Hualin Li, M Justin Iampietro
1Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Insights
An accelerated prime-boost vaccine using recombinant adenovirus vectors shows promise for protecting newborns against HIV-1. This infant vaccine strategy elicits durable immune responses, including at mucosal surfaces.
Area of Science:
- Vaccinology
- Immunology
- Pediatrics
Background:
- Infant HIV-1 prevention requires early mucosal immunity.
- Recombinant adenovirus (rAd) vectors induce immune responses but haven't been studied in infants.
- Developing a pediatric HIV-1 vaccine is crucial to prevent mother-to-child transmission.
Purpose of the Study:
- To evaluate the immunogenicity of rAd vectors in neonatal rhesus monkeys.
- To assess the potential of an accelerated heterologous prime-boost regimen for a pediatric HIV-1 vaccine.
Main Methods:
- Neonatal rhesus monkeys received a single rAd26 injection or an accelerated rAd35/rAd26 prime-boost regimen.
- Gag-specific cellular and humoral immune responses were measured.
- Mucosal immune responses were assessed over 1 year.
Main Results:
- A single rAd26 injection induced transient Gag-specific cellular immunity.
- The rAd35/rAd26 prime-boost regimen elicited potent, durable Gag-specific cellular and humoral immunity.
- Mucosal immune responses persisted for up to 1 year in the prime-boost group.
Conclusions:
- An accelerated heterologous rAd prime-boost strategy is a potential candidate for a newborn HIV-1 vaccine.
- This approach can induce robust and lasting mucosal immunity in neonates.
- Further research into rAd-based pediatric HIV-1 vaccines is warranted.
Abstract:
A pediatric human immunodeficiency virus type 1 (HIV-1) vaccine would be desirable to protect infants against HIV-1 transmission from breast-feeding. Such a vaccine would need to induce protective immunity at mucosal surfaces in neonates as soon as possible after birth. Recombinant adenovirus (rAd) vectors have been shown to elicit potent systemic and mucosal virus-specific immune responses in adult nonhuman primates and humans, but these vectors have not previously been comprehensively studied in infants. In this study, we demonstrate that a single injection of rAd26 encoding simian immunodeficiency virus mac239 (SIVmac239) Gag on the day of birth elicited detectable Gag-specific cellular immune responses in rhesus monkeys, but these responses were transient and waned quickly. In contrast, an accelerated heterologous prime-boost regimen involving administration of rAd35 at birth and rAd26 at 4 weeks of life elicited potent and durable Gag-specific cellular and humoral immune responses in neonatal rhesus monkeys, including mucosal responses that remained detectable at 1 year of age. These results suggest the potential of an accelerated heterologous rAd prime-boost regimen as a candidate HIV-1 vaccine for newborns.
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