Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice

Flavia Chiuppesi, Felix Wussow, Louise Scharf, Heidi Contreras, Han Gao, Zhuo Meng, Jenny Nguyen, Peter A Barry, Pamela J. Bjorkman, Don J. Diamond

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC. Utilizing a recently isolated anti-PC NAb, we produced highly pure soluble PC protein that displayed conformational and linear neutralizing epitopes, interfered with HCMV entry, and was recognized by antibodies induced by HCMV during natural infection. Mice vaccinated by different immunization routes with the purified PC protein in combination with a clinically approved adjuvant formulation elicited high-titer and durable HCMV NAb. While MVA-PC and soluble PC protein either alone or in combination elicited robust HCMV NAb, significantly different potencies of these vaccine approaches were observed in dependence on immunization schedule. Using only two immunizations, vaccination with MVA-PC alone or prime-boost combinations of MVA-PC and PC protein was significantly more effective in stimulating HCMV NAb than immunization with PC protein alone. In contrast, with three immunizations, NAb induced by soluble PC protein either alone or combined with two boosts of MVA-PC increased to levels that exceeded NAb titer stimulated by MVA-PC alone. These results provide insights into the potency of soluble protein and MVA to elicit NAb by the HCMV PC via homologous and heterologous prime-boost immunization, which may contribute to develop clinically deployable vaccine strategies to prevent HCMV infection.

Original languageEnglish (US)
Article numbere0183377
JournalPLoS One
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2017

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Human herpesvirus 5
Vaccinia
Vaccinium
Immunization
Neutralizing Antibodies
Cytomegalovirus
neutralizing antibodies
Vaccines
vaccines
immunization
mice
Proteins
proteins
Cytomegalovirus Infections
Vaccine Potency
Immunization Schedule
neutralization
Epitopes
epitopes
adjuvants

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice. / Chiuppesi, Flavia; Wussow, Felix; Scharf, Louise; Contreras, Heidi; Gao, Han; Meng, Zhuo; Nguyen, Jenny; Barry, Peter A; Bjorkman, Pamela J.; Diamond, Don J.

In: PLoS One, Vol. 12, No. 8, e0183377, 01.08.2017.

Research output: Contribution to journalArticle

Chiuppesi, Flavia ; Wussow, Felix ; Scharf, Louise ; Contreras, Heidi ; Gao, Han ; Meng, Zhuo ; Nguyen, Jenny ; Barry, Peter A ; Bjorkman, Pamela J. ; Diamond, Don J. / Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice. In: PLoS One. 2017 ; Vol. 12, No. 8.
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