Compositions and methods for promoting immune responses to human immunodeficiency virus
This disclosure relates to methods of promoting immune responses against HIV and compositions related thereto. In certain embodiments, this disclosure relates to methods of vaccinating for HIV comprising administering to the subject a priming composition followed by a boosting composition. In certain embodiments, the priming composition comprises a recombinant virus such as recombinant MVA that encodes an Env protein of HIV or segment thereof. In certain embodiments, the boosting composition comprises a trimeric cyclically permuted gp120 chimeric protein reported herein or DNA encoding the same.
1. A method of vaccinating comprising:
i) administering to a subject a nucleic acid and/or recombinant virus that encodes an HIV Env protein or segment thereof under conditions such that virus-like particles with surface gp120 proteins are formed in the subject;
ii) administering to the subject an effective amount of a chimeric protein comprising an amino acid sequence selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, and;
wherein administering is to the buccal cavity propelled through the skin or soft tissue lining of the mouth with pressure.
2. The method of claim 1 , wherein administering to the subject an effective amount of the chimeric protein is more than one week after administering to a subject a nucleic acid or recombinant virus that encodes HIV Env protein or segment thereof.
3. A composition comprising a chimeric protein comprising an amino acid sequence
(SEQ ID NO: 2)
EEDPCACESLVKFQAKVEGLLQALTRKLEAVSKRLAILENTVVASSEG
TMMRGELKNCSFNMTTELRDKKQKVYSLFYRLDVVQINENQGNRSNNS
NKEYRLINCNTSAITQACPKVSFEPIPIHYCAPAGFAILKCKDKKFNG
TGPCPSVSTVQCTHGIKPVVSTQLLLNGSLAEEEVMIRSENITNNAKN
ILVQFNTPVQINCTRPNNNTRKSIRIGPGQAFYATGDIIGDIRQAHCN
VSKATWNETLGKVVKQLRKHFGNNTIIRFANSSGGDLEVTTHSFNCGG
EFFYCNTSGLFNSTWISNTSVQGSNSTGSNDSITLPCRIKQIINMAAA
WQRIGQAMYAPPIQGVIRCVSNITGLILTRDGGSTNSTTETFRPGGGD
MRDNWRSELYKYKVVKIEPLGVAPTRAKRRVVGREKRGSAGSAGSSRS
AGSAGSAGSEIHLENVTEEFNMWKNNMVEQMFITDIISLWDQSLKPCV
KLTPLCVTLQCTNVTNNITDDAAA.
4. A composition comprising a chimeric protein comprising an amino acid sequence
(SEQ ID NO: 3)
EEDPCACESLVKFQAKVEGLLQALTRKLEAVSKRLAILENTVVASSVN
VTNGEEIKNCSFNATTEIRDKKQKVYALFYRLDIVPLEEERKGNSSKY
RLINCNTSAITQACPKVTFDPIPIHYCAPAGYAILKCNNKTFNGTGPC
NNVSTVQCTHGIKPVVSTQLLLNGSLAEGEIIIRSENLTNNVKTIIVH
LNESVEIVCTRPNNNTRKSIRIGPGQTFYATGDIIGNIRQAYCNIKKD
DWIRTLQRVGKKLAEHFPRRIINFTSPAGGDLEITTHSFNCRGEFFYC
NTSSLFNSTYNPNDTNSNSSSSNSSLDITIPCRIKQIINMWQEVGRAM
YAPPIEGNITCKSNITGLLLVRDGGVESNETEIFRPGGGDMRNNWRSE
LYKYKVVEIKPLGIAPTAAKRRVVEREKRGSAGSAGSSRSAGSAGSAG
SEMVLENVTENFNMWKNDMVEQMHEDVISLWDQSLKPCVKLTPLCVTL
ECRQVNTTNATSAAA.
5. A composition comprising a chimeric protein comprising an amino acid sequence
(SEQ ID NO: 4)
EEDPCACESLVKFQAKVEGLLQALTRKLEAVSKRLAILENTVVASSVN
VTNGEVMKNCSFNATTELKDKKHKVHALFYKLDVVPLNGNSSSSGEYR
LINCNTSAITQACPKVSFDPIPLHYCAPAGFAILKCNNKTFNGTGPCR
NVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTNNAKTIIVHL
NESVNINCTRPNNNTRKSIRIGPGQTFYATGDIIGNIRQAHCNINESK
WNNTLQKVGEELAKHFPSKTIKFEPSSGGDLEITTHSFNCRGEFFYCN
TSDLFNGTYRNGTYNHTGRSSNGTITLQCKIKQIINMWQEVGRAIYAP
PIEGEITCNSNITGLLLLRDGGQSNETNDTETFRPGGGDMRDNWRSEL
YKYKVVEIKPLGVAPTEAKRRVVEREKRGSAGSAGSSRSAGSAGSAGS
EMVLANVTENFNMWKNDMVEQMHEDIISLWDESLKPCVKLTPLCVTLN
CTNVKGNESDTAAA.
6. A composition comprising a chimeric protein comprising an amino acid sequence
(SEQ ID NO: 5)
EEDPCACESLVKFQAKVEGLLQALTRKLEAVSKRLAILENTVVASSVN
VTNGEEIKNCSFNTTTEIRDKKQKEYALFYRLDIVPLNEERKGNSSEY
RLINCNTSTITQACPKVSFDPIPIHYCAPAGYAILKCNNKTFNGTGPC
NNVSTVQCTHGIKPVVSTQLLLNGSLAEEEIIIRSENLTNNAKTIIVH
LNESVEINCTRPNNNTRKSIRIGPGQTFYATGDIIGDIRQAHCNISES
KWNKTLQRVSKKLKEHFPNKTIKFAPSSGGDLEITTHSFNCRGEFFYC
NTSKLFNSTYNNNTSNSTITLPCRIKQIINMWQEVGRAMYAPPIAGNI
TCKSNITGLLLTRDGGNNNNTTETFRPGGGDMRDNWRSELYKYKVVEI
KPLGIAPTKAKRRVVEREKRGSAGSAGSSRSAGSAGSAGSEMVLENVT
ENFNMWKNDMVDQMHEDTTSLWDQSLKPCVKLTPLCVTLNCTNVNVTN
ATSAAA.