Cryptic epitope for antibodies should not be forgotten in vaccine design

Good, Michael F.; Yanow, Stephanie K.

doi:10.1586/14760584.2016.1154791

Cited by 8 publications

(11 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of these one-third are sub-unit vaccines that contain highly immunogenic immunodominant antigens capable of producing antibodies to a single-strain of an organism. 2 , 3 However, for several infectious diseases this approach is ineffective or is associated with major disadvantages. The challenge is that many organisms are antigenically variable and due to their diversity, polyvalent vaccines have been developed.…”

mentioning

confidence: 99%

“…An alternative approach is to use cryptic epitopes because these are poorly immunogenic in the native organism and they are thus not under immune selection pressure. 3 Although they may not be recognised as a result of natural infection, 4 they can be highly immunogenic when presented in isolation such as a peptide or a recombinant polypeptide fragment. Furthermore, because they are conserved they may be able to induce strain-transcending immunity.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Contribution of cryptic epitopes in designing a group A streptococcal vaccine

Ozberk

Pandey

Good

2018

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

A successful vaccine needs to target multiple strains of an organism. Streptococcus pyogenes is an organism that utilizes antigenic strain variation as a successful defence mechanism to circumvent the host immune response. Despite numerous efforts, there is currently no vaccine available for this organism. Here we review and discuss the significant obstacles to vaccine development, with a focus on how cryptic epitopes may provide a strategy to circumvent the obstacles of antigenic variation.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Contribution of cryptic epitopes in designing a group A streptococcal vaccine

Ozberk

Pandey

Good

2018

Human Vaccines & Immunotherapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In line with this, C162 of UL128, which is centrally positioned within the 13B5 target sequence, was previously shown to form a disulfide bond with a cysteine residue in gL (35), highlighting that the 13B5 binding sequence is located at a critical interaction site of the PC subunits. In addition, the observation that antibodies in HCMV ϩ individuals react only minimally with peptides containing the 13B5 target sequence may suggest that this sequence is only minimally immunogenic or only rarely recognized by the immune system during natural HCMV infection, which is consistent with characteristics of an immunologically "cryptic" epitope (45). Epitope crypticity is a common pattern of immune evasion and has been described for many other pathogens such as HIV, influenza virus, dengue virus, Plasmodium falciparum, and Bacillus anthracis (45)(46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 92%

“…In addition, the observation that antibodies in HCMV ϩ individuals react only minimally with peptides containing the 13B5 target sequence may suggest that this sequence is only minimally immunogenic or only rarely recognized by the immune system during natural HCMV infection, which is consistent with characteristics of an immunologically "cryptic" epitope (45). Epitope crypticity is a common pattern of immune evasion and has been described for many other pathogens such as HIV, influenza virus, dengue virus, Plasmodium falciparum, and Bacillus anthracis (45)(46)(47)(48)(49). While it appears contradictory how the 13B5 epitope can be immunologically cryptic and at the same time a target of potent NAb, this could be explained by differences in the accessibility of the 13B5 binding site during natural HCMV infection.…”

Section: Discussionmentioning

confidence: 92%

“…While the details may be different, a parallel to the HIV case can be made in the comparison of the putative low immunogenicity of the 13B5 epitope and the potent ability of the 13B5 antibody to neutralize infection. The 13B5 epitope could be of low immunogenicity because it competes for antibody access with immunodominant nonneutralizing epitopes that are localized in close proximity to the 13B5 NAb binding site (45). However, only a very small amount of the 13B5 antibody may be required for potent neutralization, which could be associated with either the high affinity of the 13B5 antibody or the small amounts of the PC in HCMV virions (53).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a Continuous Neutralizing Epitope within UL128 of Human Cytomegalovirus

Chiuppesi

Kaltcheva

Zhao

et al. 2017

J Virol

View full text Add to dashboard Cite

As human cytomegalovirus (HCMV) is the most common infectious cause of fetal anomalies during pregnancy, development of a vaccine that prevents HCMV infection is considered a global health priority. Although HCMV immune correlates of protection are only poorly defined, neutralizing antibodies (NAb) targeting the envelope pentamer complex (PC) composed of the subunits gH, gL, UL128, UL130, and UL131A are thought to contribute to the prevention of HCMV infection. Here, we describe a continuous target sequence within UL128 that is recognized by a previously isolated potent PC-specific NAb termed 13B5. By using peptide-based scanning procedures, we identified a 13-amino-acid-long target sequence at the UL128 C terminus that binds the 13B5 antibody with an affinity similar to that of the purified PC. In addition, the 13B5 binding site is universally conserved in HCMV, contains a previously described UL128/gL interaction site, and interferes with the 13B5 neutralizing function, indicating that the 13B5 epitope sequence is located within the PC at a site of critical importance for HCMV neutralization. Vaccination of mice with peptides containing the 13B5 target sequence resulted in the robust stimulation of binding antibodies and, in a subset of immunized animals, in the induction of detectable NAb, supporting that the identified 13B5 target sequence constitutes a PC-specific neutralizing epitope. These findings provide evidence for the discovery of a continuous neutralizing epitope within the UL128 subunit of the PC that could be an important target of humoral immune responses that are involved in protection against congenital HCMV infection.IMPORTANCE Neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) envelope pentamer complex (PC) are thought to be important for preventing HCMV transmission from the mother to the fetus, thereby mitigating severe developmental disabilities in newborns. However, the epitope sequences within the PC that are recognized by these potentially protective antibody responses are only poorly defined. Here, we provide evidence for the existence of a highly conserved, continuous, PC-specific epitope sequence that appears to be located within the PC at a subunit interaction site of critical importance for HCMV neutralization. These discoveries provide insights into a continuous PC-specific neutralizing epitope, which could be an important target for a vaccine formulation to interfere with congenital HCMV infection.

show abstract