Human Immunodeficiency Virus Type 1 (HIV‐1) gp120–Specific Antibodies in Neonates Receiving an HIV‐1 Recombinant gp120 Vaccine

Abstract

Infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers were immunized at birth and at ages 4, 12, and 20 weeks with low-, medium-, or high-dose recombinant gp120 vaccine with MF59 adjuvant (HIV-1(SF-2); n=52) or with MF59 alone as a placebo (n=9). An accelerated schedule (birth and ages 2, 8, and 20 weeks) was used for an additional 10 infants receiving the defined optimal dose and for 3 infants receiving placebo. At 24 weeks, anti-gp120 ELISA titers were greater for vaccine-immunized than for placebo-immunized infants on both schedules, and 87% of vaccinees had a vaccine-induced antibody response. At 12 weeks, antibody titers of infants on the accelerated vaccine schedule exceeded those of infants receiving placebo (4949 vs. 551; P=.01), and 63% of the vaccinees met the response criteria. Thus, an accelerated schedule of gp120 vaccinations generated an antibody response to HIV-1 envelope distinct from transplacental maternal antibody by age 12 weeks. These results provide support for further studies of vaccine strategies to prevent mother-to-infant HIV-1 transmission.

Immunization of Newborn Rhesus Macaques with Simian Immunodeficiency Virus (SIV) Vaccines Prolongs Survival after Oral Challenge with Virulent SIVmac251

“…We demonstrated that both vaccines, MVA-SIVgpe and SIVmac1A11, elicited rapid immune responses in infant macaques. Thus, the immune system of newborn monkeys is competent to make immune responses, a finding in agreement with the results of HIV-1 vaccine trials in human neonates (4,26). Neither of the two vaccines in our study prevented SIV-infection after oral challenge at 4 weeks of age.…”

“…Both groups also developed similar levels of SIV-specific antibodies. This finding is consistent with the antibody responses observed in infants, born to HIV-infected women, who were given an HIV-1 recombinant gp120 vaccine (26). In a measles model in macaques, immunization of infant (51) or juvenile monkeys (39) with an MVA-based measles vaccine was effective in the presence of passively acquired neutralizing antibody.…”

“…In a measles model in macaques, immunization of infant (51) or juvenile monkeys (39) with an MVA-based measles vaccine was effective in the presence of passively acquired neutralizing antibody. In addition, a trial in which human newborns with maternal antibodies received an accelerated immunization schedule with recombinant HIV-1 gp120 also found that the presence of maternal antibodies did not inhibit a de novo antibody response (26). In the present study in infant macaques, although no effect on vaccine efficacy was observed, our observations suggest that maternal antibodies caused differences in the antibody quality, in particular with respect to avidity, after MVA-SIVgpe immunization (Fig.…”

Improving vaccine delivery using novel adjuvant systems

“…37 Vaccination studies for cytomegalovirus and HIV also support further research into the use of MF59 adjuvant. 38,39 QS21 is also a component of ASO2 adjuvant. Ongoing vaccination studies of QS21 adjuvant involve breast cancer, HIV, prostate cancer, colorectal cancer and small cell lung cancer responsive to initial therapy.…”

Accelerated Heterologous Adenovirus Prime-Boost SIV Vaccine in Neonatal Rhesus Monkeys

“…First, neonates have immature immune systems, and it is unclear whether vaccine vectors that are immunogenic in adults will be comparably immunogenic in neonates. Very few studies of HIV-1 or simian immunodeficiency virus (SIV) vaccines have been performed with neonatal rhesus monkeys (23,37,38,40) and humans (8,25,26). Moreover, heterologous prime-boost regimens that have been studied with adult rhesus monkeys (5,7,22) typically require 6 months or longer to induce peak immune responses, and such timing would not be optimal for a pediatric HIV-1 vaccine.…”