An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge

Paul J F Rider; Mohd Kamil; Ilknur Yilmaz; Habibe N Atmaca; Merve Kalkan-Yazici; Mehmet Ziya Doymaz; Konstantin G Kousoulas; Ahmed S I Aly

doi:10.3390/vaccines10020300

An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge

Vaccines (Basel). 2022 Feb 16;10(2):300. doi: 10.3390/vaccines10020300.

Authors

Paul J F Rider^{1

2}, Mohd Kamil³, Ilknur Yilmaz³, Habibe N Atmaca³, Merve Kalkan-Yazici⁴, Mehmet Ziya Doymaz⁴, Konstantin G Kousoulas^{1

2}, Ahmed S I Aly³

Affiliations

¹ Division of Biotechnology and Molecular Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.
² Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA.
³ Aly Lab, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34820, Turkey.
⁴ Microbiology Lab, Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul 34820, Turkey.

Abstract

Here, we present the construction of an attenuated herpes simplex virus type-1 (HSV-1)-vectored vaccine, expressing three liver-stage (LS) malaria parasite exported proteins (EXP1, UIS3 and TMP21) as fusion proteins with the VP26 viral capsid protein. Intramuscular and subcutaneous immunizations of mice with a pooled vaccine, composed of the three attenuated virus strains expressing each LS antigen, induced sterile protection against the intravenous challenge of Plasmodium yoelii 17X-NL salivary gland sporozoites. Our data suggest that this malaria vaccine may be effective in preventing malaria parasite infection using practical routes of immunization in humans.

Keywords: EXP1; HSV-1; TMP21; UIS3; VC2; intramuscular; liver stage; malaria vaccine; subcutaneous; viral vector.

Abstract

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