Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez, David R.; Permar, Sallie R.; Fouda, Genevieve G.

doi:10.1128/cvi.00565-15

Cited by 39 publications

(38 citation statements)

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“…Our results strongly suggesting differences in vaccine-elicited antibody responses between adults and infants corroborate previous findings demonstrating differences in the pathogenesis and immune response to HIV infection between adults and children, such as possible differences in the development of antibody responses following adult and pediatric HIV infection (36)(37)(38). Overall, this body of data indicates that vaccine findings in adult populations may not predict infant responses, emphasizing the need to test promising HIV vaccine strategies in pediatric populations.…”

Section: Discussionsupporting

confidence: 87%

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine

McGuire

Fong²,

Toote

et al. 2018

J Virol

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In the RV144 vaccine trial, IgG responses against the HIV envelope variable loops 1 and 2 (V1V2) were associated with decreased HIV acquisition risk. We previously reported that infants immunized with an MF59-adjuvanted rgp120 vaccine developed higher-magnitude anti-V1V2 IgG responses than adult RV144 vaccinees. To determine whether the robust antibody response in infants is due to differences in vaccine regimens or to inherent differences between the adult and infant immune systems, we compared Env-specific IgG responses in adults and infants immunized with the same MF59- and alum-adjuvanted HIV envelope vaccines. At peak immunogenicity, the magnitudes of the gp120- and V1V2-specific IgG responses were comparable between adults and infants immunized with the alum/MNrgp120 vaccine (gp120 median fluorescence intensities [FIs] in infants = 7,118 and in adults = 11,510, = 0.070; V1V2 median MFIs of 512 [infants] and 804 [adults], = 0.50), whereas infants immunized with the MF59/SF-2 rgp120 vaccine had higher-magnitude antibody levels than adults (gp120 median FIs of 15,509 [infants] and 2,290 [adults], < 0.001; V1V2 median FIs of 23,926 [infants] and 1,538 [adults]; < 0.001). Six months after peak immunogenicity, infants maintained higher levels Env-specific IgG than adults. Anti-V1V2 IgG3 antibodies that were associated with decreased HIV-1 risk in RV144 vaccinees were present in 43% of MF59/rgp120-vaccinated infants but only in 12% of the vaccinated adults ( = 0.0018). Finally, in contrast to the rare vaccine-elicited Env-specific IgA in infants, rgp120 vaccine-elicited Env-specific IgA was frequently detected in adults. Our results suggest that vaccine adjuvants differently modulate gp120-specific antibody responses in adults and infants and that infants can robustly respond to HIV Env immunization. More than 150,000 pediatric HIV infections occur yearly, despite the availability of antiretroviral prophylaxis. A pediatric HIV vaccine could reduce the number of these ongoing infant infections and also prime for long-term immunity prior to sexual debut. We previously reported that immunization of infants with an MF59-adjuvanted recombinant gp120 vaccine induced higher-magnitude, potentially protective anti-V1V2 IgG responses than in adult vaccinees receiving the moderately effective RV144 vaccine. In the present study, we demonstrate that the robust response observed in infants is not due to differences in vaccine regimen or vaccine dose between adults and infants. Our results suggest that HIV vaccine adjuvants may differentially modulate immune responses in adults and infants, highlighting the need to conduct vaccine trials in pediatric populations.

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Section: Discussionsupporting

confidence: 87%

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine

McGuire

Fong²,

Toote

et al. 2018

J Virol

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“…Adjuvants also affect the durability of Ab responses. In humans, MF59 (a squalene emulsion) elicits more durable Abs than aluminum salts, particularly in infants . Late gp120 boosts are currently being explored as a method of achieving better durability of gp120 Abs in RV144 participants as well as in participants in DNA/MVA vaccine trials.…”

Section: Current Goals Of Research On the Ab Component For An Aids Vamentioning

confidence: 99%

HIV/AIDS Vaccines: 2018

Robinson

2018

Clin Pharma and Therapeutics

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Human immunodeficiency virus (HIV) has infected 76 million people and killed an estimated 35 million. During its 40‐year history, remarkable progress has been made on antiretroviral drugs. Progress toward a vaccine has also been made, although this has yet to deliver a licensed product. In 2007, I wrote a review, HIV AIDS Vaccines: 2007. This review, HIV AIDS Vaccines: 2018, focuses on the progress in the past 11 years. I begin with key challenges for the development of an AIDS vaccine and the lessons learned from the six completed efficacy trials, only one of which has met with some success.

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“…The disease course in HIV-infected infants is dramatically different from that of HIV-infected adults (3). Without treatment, vertically HIV-infected infants tend to have higher plasma viral RNA loads, experience rapid declines in peripheral CD4+ T cell counts, and progress to AIDS more rapidly than adults (4, 5).…”

Section: Introductionmentioning

confidence: 99%

SHIV.CH505-infected infant and adult rhesus macaques exhibit similar HIV Env-specific antibody kinetics, despite distinct T-follicular helper (Tfh) and germinal center B cell landscapes

Nelson

Goswami

Dennis

et al. 2019

Preprint

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Word count: 224 22 Text Word count: 6,229 23 2 Abstract 24Pediatric HIV infection remains a large global health concern despite the 25 widespread use of antiretroviral therapy (ART). Thus, global elimination of pediatric HIV 26 infections will require the development of novel immune-based approaches, and 27 understanding infant immunity to HIV is critical to guide the rational design of these 28 intervention strategies. Despite their immunological immaturity, HIV-infected children 29 develop broadly neutralizing antibodies (bnAbs) more frequently and earlier than adults 30 do. Furthermore, T-follicular helper (Tfh) cells have been associated with bnAb 31 development in HIV-infected children and adults. To further our understanding of age-32 related differences in the development of HIV-specific immunity, we evaluated the 33 generation of virus-specific humoral immune responses in infant (n=6) and adult (n=12) 34 rhesus macaques (RMs) infected with a transmitted/founder (T/F) simian-human 35 immunodeficiency virus (SHIV.C.CH505). The plasma HIV envelope-specific IgG 36 antibody kinetics were similar in SHIV-infected infant and adult RMs, with no significant 37 differences in the magnitude or breadth of these responses. Interestingly, autologous 38 tier 2 virus neutralization responses also developed with similar frequency and kinetics 39 in infant and adult RMs, despite infants exhibiting significantly higher Tfh and germinal 40 center B cell frequencies compared to adults. Our results indicate that the humoral 41 immune response to SHIV infection develops with similar kinetics among infant and 42 adult RMs, suggesting that the early life immune system is equipped to respond to HIV-43 1 and promote the production of neutralizing HIV antibodies.44 45 46 Importance 47There is a lack of understanding on how the maturation of the infant immune system 48 influences immunity to HIV infection, or how these responses differ from those of adults. 49Improving our knowledge of infant HIV immunity will help guide antiviral intervention 50 strategies that take advantage of the unique infant immune environment to successfully 51 elicit protective immune responses. We utilized a rhesus macaque model of SHIV 52 infection as a tool to distinguish the differences in HIV humoral immunity in infants 53 versus adults. Here, we demonstrate that the kinetics and quality of the infant humoral 54 immune response to HIV are highly comparable to that of adults during the early phase 55 of infection, despite distinct differences in their Tfh responses, indicating that slightly 56 different mechanisms may drive infant and adult humoral immunity. 57 Word count: 129/150 58 59

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Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Cited by 39 publications

References 100 publications

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine

HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine

HIV/AIDS Vaccines: 2018

SHIV.CH505-infected infant and adult rhesus macaques exhibit similar HIV Env-specific antibody kinetics, despite distinct T-follicular helper (Tfh) and germinal center B cell landscapes

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