Recombinant zika vaccines

A nucleic acid molecule comprising (i) first nucleic acid sequence encoding at least one E-protein of a Zika virus or a functional fragment of an E-protein of a Zika virus, and (ii) a second nucleic acid sequence encoding at least one E-protein signal sequence for a Zika virus E-protein or a functional fragment of an E-protein of a Zika virus, and optionally comprising (iii) a third nucleic acid sequence encoding at least one pre-membrane protein of a Zika virus or a functional fragment of a pre-membrane protein of a Zika virus, and optionally comprising (iv) a fourth nucleic acid sequence encoding at least one pre-membrane protein signal sequence for a Zika virus pre-membrane protein or a functional fragment of a pre-membrane protein signal sequence of a Zika virus, wherein the first and optionally the second and/or the third and/or the fourth nucleic acid sequence is/are independently derived from any one of SEQ ID NOs:

• 1 to 13 and 67 to 87, and wherein the nucleic acid molecule does not comprise a nucleic acid sequence encoding a C-protein of a flavivirus, and
• (a) wherein the nucleic acid molecule additionally comprises a mutation within the first nucleic acid sequence at the position encoding amino acid position L107 of the E-protein of a Zika virus or the functional fragment of an E-protein of a Zika virus in comparison to the sequence of any one of SEQ ID NOs:
• 27 to 39, 40 to 52, 109 to 129 and 130 to 150, and optionally wherein the first nucleic acid sequence comprises a sequence encoding the stem anchor region of the E-protein of a Zika virus encoded by any one of SEQ ID NOs:
• 1 to 13 and 67 to 87, or wherein the E-protein of a Zika virus comprises a heterologous stem-anchor region selected from any one of SEQ ID NOs:
• 185 to 191, or a sequence having at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence homology thereto, or
• (b) wherein the nucleic acid molecule does not comprise a nucleic acid sequence encoding a stem anchor region of the E-protein of a Zika virus or a heterologous stem-anchor region for an E-protein of a Zika virus, or
• (c) wherein the nucleic acid molecule does not comprise a further nucleic acid sequence encoding a non-structural protein of a flavivirus.

A method for producing a recombinant chimeric virus, the method comprising the following steps:

• (i) inserting a nucleic acid molecule encoding an E-protein or a soluble E-protein of a Zika virus into a measles virus scaffold vector backbone to operably link the nucleic acid molecule and the vector backbone to obtain a recombinant chimeric virus sequence;
• (ii) infecting at least one host cell with at least one recombinant chimeric virus sequence obtained in step (i) to obtain a virus sample;
• (iii) clarifying the virus sample of step (ii);
• (iv) purifying the clarified virus sample of step (iii);
• (v) optionally:
• formulating the at least one recombinant chimeric virus with at least one pharmaceutically and/or veterinarially acceptable carrier and/or excipient;
• and
• (vi) obtaining a recombinant chimeric virus.