Infant HIV Type 1 gp120 Vaccination Elicits Robust and Durable Anti-V1V2 Immunoglobulin G Responses and Only Rare Envelope-Specific Immunoglobulin A Responses

Fouda, Genevieve G.; Cunningham, Coleen K.; McFarland, Elizabeth J.; Borkowsky, William; Muresan, Petronella; Pollara, Justin; Song, Lin; Liebl, Brooke E.; Whitaker, Kaylan; Shen, Xiaoying; Vandergrift, Nathan; Overman, R. Glenn; Yates, Nicole L.; Moody, M. Anthony; Fry, Carrie; Kim, Jerome H.; Michael, Nelson L.; Robb, Merlin L.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Rerks-Ngarm, Supachai; Liao, Hua‐Xin; Haynes, Barton F.; Montefiori, David C.; Ferrari, Guido; Tomaras, Georgia D.; Permar, Sallie R.

doi:10.1093/infdis/jiu444

Cited by 53 publications

(66 citation statements)

References 29 publications

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“…Recent works have indicated that the neonatal immune system is equipped to respond to HIV antigen exposure in a way that induces broad neutralizing antibody responses (55). In addition, infants can develop robust antibody responses that are equal to or higher in magnitude than adult vaccine responses that were associated with a reduced risk of sexual HIV infection (74). Importantly, because immune pathways that lead to protective immune responses may differ between infants and adults, HIV vaccine strategies may need to be tailored to the infant immune landscape in order to direct the development of protective HIV immunity in early life.…”

Section: Resultsmentioning

confidence: 99%

“…Reanalysis of the antibody responses elicited by infant Env vaccination revealed that infants developed robust Env-specific antibody responses to these first-generation HIV Env vaccines. At 1 year of age, the majority of the maternally acquired antibodies had waned, and vaccine Env-specific IgG responses were significantly higher in vaccinees than in placebo recipients (74). All vaccine regimens induced a frequency of V1V2 response in vaccinees similar to or higher than that in RV144 vaccinees (Fig.…”

Section: Hiv Vaccine Responses In Infants and Adultsmentioning

confidence: 86%

“…The IgG subclass distribution of V1V2-IgG antibodies was assessed among PACTG 230 participants immunized with the Chiron vaccine and in placebo recipients. The majority of infants had IgG1 antibodies against gp70 B case A2 V1V2, but 42% of them also had V1V2-specific IgG3 antibodies at peak immunogenicity (74). However, this response was short-lived, as 8 months after vaccination, V1V2-specific IgG3 antibodies were no longer detected in infants.…”

Section: Hiv Vaccine Responses In Infants and Adultsmentioning

confidence: 99%

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Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez

Permar

Fouda

2016

Clin Vaccine Immunol

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Extensive studies have demonstrated that infant immune responses are distinct from those of adults. Despite these differences, infant immunization can elicit protective immune responses at levels comparable to or, in some cases, higher than adult immune responses to many vaccines. To date, only a few HIV vaccine candidates have been tested in infant populations, and none of them evaluated vaccine efficacy. Recent exciting studies showing that HIV-infected infants can develop broad neutralizing antibody responses and that some HIV vaccine regimens can elicit high levels of potentially protective antibodies in infants provide support for the development and testing of HIV vaccines in pediatric populations. In this review, we discuss the differences in adult and infant immune responses in the setting of HIV infection and vaccination.

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Section: Resultsmentioning

confidence: 99%

Section: Hiv Vaccine Responses In Infants and Adultsmentioning

confidence: 86%

Section: Hiv Vaccine Responses In Infants and Adultsmentioning

confidence: 99%

See 1 more Smart Citation

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Martinez

Permar

Fouda

2016

Clin Vaccine Immunol

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“…Many vaccine design strategies are focused on the HIV-1 Env protein, which is the trimeric antigen present on the viral surface. Some Env immunogens, including proteins used in the RV144 trial, are based on a soluble monomeric form of the gp120 subunit of the trimer (1)(2)(3)(4)(5)(6)(7). An alternative approach involves soluble oligomeric gp140 proteins that contain both gp120 and the external component of the gp41 subunit (8)(9)(10)(11)(12)(13).…”

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confidence: 99%

Native Conformation and Canonical Disulfide Bond Formation Are Interlinked Properties of HIV-1 Env Glycoproteins

Cupo

Ringe

et al. 2016

J Virol

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We investigated whether there is any association between a native-like conformation and the presence of only the canonical (i.e., native) disulfide bonds in the gp120 subunits of a soluble recombinant human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein. We used a mass spectrometry (MS)-based method to map the disulfide bonds present in nonnative uncleaved gp140 proteins and native-like SOSIP.664 trimers based on the BG505 env gene. Our results show that uncleaved gp140 proteins were not homogeneous, in that substantial subpopulations (20 to 80%) contained aberrant disulfide bonds. In contrast, the gp120 subunits of the native-like SOSIP.664 trimer almost exclusively retained the canonical disulfide bond pattern. We also observed that the purification method could influence the proportion of an Env protein population that contained aberrant disulfide bonds. We infer that gp140 proteins may always contain a variable but substantial proportion of aberrant disulfide bonds but that the impact of this problem can be minimized via design and/or purification strategies that yield native-like trimers. The same factors may also be relevant to the production and purification of monomeric gp120 proteins that are free of aberrant disulfide bonds. IMPORTANCEIt is widely thought that a successful HIV-1 vaccine will include a recombinant form of the Env protein, a trimer located on the virion surface. To increase yield and simplify purification, Env proteins are often made in truncated, soluble forms. A consequence, however, can be the loss of the native conformation concomitant with the virion-associated trimer. Moreover, some soluble recombinant Env proteins contain aberrant disulfide bonds that are not expected to be present in the native trimer. To assess whether these observations are linked, to determine the extent of disulfide bond scrambling, and to understand why scrambling occurs, we determined the disulfide bond profiles of two soluble Env proteins with different designs that are being assessed as vaccine candidates. We found that uncleaved gp140 forms heterogeneous mixtures in which aberrant disulfide bonds abound. In contrast, BG505 SOSIP.664 trimers are more homogeneous, native-like entities that contain predominantly the native disulfide bond profile. The first human immunodeficiency virus type 1 (HIV-1) vaccine trial (designated RV144) to yield one statistically significant measure of efficacy was reported in 2009 (1). Since then, attempts to substantially improve on those initial results have been ongoing. Many vaccine design strategies are focused on the HIV-1 Env protein, which is the trimeric antigen present on the viral surface. Some Env immunogens, including proteins used in the RV144 trial, are based on a soluble monomeric form of the gp120 subunit of the trimer (1-7). An alternative approach involves soluble oligomeric gp140 proteins that contain both gp120 and the external component of the gp41 subunit (8-13). The concept underlying the use of gp140 proteins is that they may ...

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“…Taken together, these studies present evidence of the multifaceted role of the HIV Env in shaping the activation state and functionality of host CD4 T cells. It is also important to note that such HIV Env-mediated immunomodulation may play a part not only in the immune dysregulation seen during HIV infection but also in the inadequate elicitation and maturation of effector and memory immune responses to many of the HIV Env-based vaccine candidates evaluated thus far (63)(64)(65).…”

Section: Discussionmentioning

confidence: 99%

HIV Envelope gp120 Alters T Cell Receptor Mobilization in the Immunological Synapse of Uninfected CD4 T Cells and Augments T Cell Activation

Deng

Mitsuki

Shen

et al. 2016

J Virol

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Infant HIV Type 1 gp120 Vaccination Elicits Robust and Durable Anti-V1V2 Immunoglobulin G Responses and Only Rare Envelope-Specific Immunoglobulin A Responses

Abstract: As exemplified by the Chiron vaccine regimen, vaccination of infants against HIV-1 can induce robust, durable Env-specific IgG responses, including anti-V1V2 IgG.

Cited by 53 publications

References 29 publications

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Contrasting Adult and Infant Immune Responses to HIV Infection and Vaccination

Native Conformation and Canonical Disulfide Bond Formation Are Interlinked Properties of HIV-1 Env Glycoproteins

HIV Envelope gp120 Alters T Cell Receptor Mobilization in the Immunological Synapse of Uninfected CD4 T Cells and Augments T Cell Activation

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