Lymphoproliferative Responses to Recombinant HIV‐1 Envelope Antigens in Neonates and Infants Receiving gp120 Vaccines

Abstract

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

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.…”

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

“…A neonatal HIV-1 vaccine that rapidly induces systemic and mucosal protective immunity would therefore represent a major advance. A variety of HIV-1 vaccine candidates have been studied with adults, but very few studies of HIV-1 vaccines have been performed in neonates (2,8,23,25,26,37,38,40). Considering the unique features of the neonatal immune system and the need to induce mucosal immune responses rapidly to protect newborns from breast milk HIV-1 transmission, it is important to investigate the immunogenicity of candidate HIV-1 vaccines directly in neonates.…”

“…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.…”

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

“…Infants were immunized with 4 vaccine doses between 0 and 20 weeks of age. Both vaccines were shown to be safe and to induce humoral and cellular immune responses (64,65). In the initial phase of the study, infants were immunized with escalating doses of vaccines to identify an "optimal vaccine dose" (63).…”

“…In the initial phase of the study, infants were immunized with escalating doses of vaccines to identify an "optimal vaccine dose" (63). Interestingly, infants who received the lowest vaccine dose had a higher frequency of T cell lymphoproliferative responses than infants immunized with higher vaccine doses (65), suggesting that low vaccine doses may be required in early life. HIV vaccine safety in infants was also demonstrated in PACTG 326 (66).…”