HIV researchers everywhere are grateful to Science for featuring HIV in their 28 June issue to coincide with this year's AIDS Congress in Barcelona. However, there are two points in Jon Cohen's article “Monkey puzzles” (News Focus, p. [2325][1]) that require further consideration. First, the statement that “monkey studies with AIDS vaccines have completely failed to elicit antibodies that can neutralize the virus” (p. [2325][1]) is not consistent with the published data. Many papers have shown the ability of envelope-based HIV vaccines to induce antibodies that neutralize T cell line-adapted virus isolates, although neutralization of primary CCR5-dependent HIV-1 isolates was rarely observed. In contrast, our papers clearly show that immunization of Rhesus macaques with a plasmid DNA vaccine prime followed by a recombinant oligomeric V2 loop-deleted SF162 envelope protein boost is capable of inducing serum antibodies that neutralize multiple primary isolates of HIV-1 that are both antigenically distinct and CCR5-dependent ([1][2], [2][3]). To our knowledge, this was the first time that a vaccine-induced immune response was shown to be capable of broad primary isolate neutralization, and we are dismayed that this significant milestone in HIV vaccine research is overlooked by a review in a widely read journal. Second, the table on p. [2326][1] (“AIDS Vaccine Pipeline”) does not include vaccines in preclinical testing sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) in collaboration with Wyeth Laboratories and Chiron Corporation (a version of the DNA prime-protein boost vaccine mentioned above). These IND-enabling preclinical studies are supported by the NIH HIV Vaccine Design and Development Team Contracts, which have been well publicized. We believe that underreporting the breadth and scope of NIAID's commitment to research and development of HIV vaccines does this important agency a great disservice. 1. [↵][4]1. S. Cherpelis 2. et al. , J. Virol. 75, 1547 (2001). [OpenUrl][5][Abstract/FREE Full Text][6] 2. [↵][7]1. S. W. Barnett 2. et al. , J. Virol. 75, 5526 (2001). [OpenUrl][8][Abstract/FREE Full Text][9] # Response {#article-title-2} The pipeline table should have made clear that the list was not all-inclusive. The Chiron and Wyeth studies appear on a more comprehensive pipeline table that accompanied an article that I wrote for the 2 March 2001 issue (“AIDS vaccines show promise after years of frustration,” News Focus, p. [1686][10]). That article includes a prediction from Chiron that its vaccine would be in human trials in 2002 (which does not look likely now), and it describes the work in some detail. The assertion that antibodies have “completely failed” to neutralize the virus in monkey studies may be a bit of an overstatement, but not much, as is clear simply by looking closely at the counterevidence Donnelly et al. present. First, they cite in vitro studies of antibodies from human HIV vaccine tests—which, if anything, underscore the difficulties antibodies have in stopping real-world isolates of the virus. Their own monkey data, from two animals, did not reach statistical significance, and, as far as I can tell, have not been independently replicated. [1]: /lookup/doi/10.1126/science.296.5577.2325 [2]: #ref-1 [3]: #ref-2 [4]: #xref-ref-1-1 View reference 1 in text [5]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BVirology%26rft.stitle%253DJ.%2BVirol.%26rft.issn%253D0022-538X%26rft.aulast%253DCherpelis%26rft.auinit1%253DS.%26rft.volume%253D75%26rft.issue%253D3%26rft.spage%253D1547%26rft.epage%253D1550%26rft.atitle%253DDNA%2BVaccination%2Bwith%2Bthe%2BHuman%2BImmunodeficiency%2BVirus%2BType%2B1%2BSF162%257BDelta%257DV2%2BEnvelope%2BElicits%2BImmune%2BResponses%2BThat%2BOffer%2BPartial%2BProtection%2Bfrom%2BSimian%252FHuman%2BImmunodeficiency%2BVirus%2BInfection%2Bto%2BCD8%252B%2BT-Cell-Depleted%2BRhesus%2BMacaques%26rft_id%253Dinfo%253Adoi%252F10.1128%252FJVI.75.3.1547-1550.2001%26rft_id%253Dinfo%253Apmid%252F11152527%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoianZpIjtzOjU6InJlc2lkIjtzOjk6Ijc1LzMvMTU0NyI7czo0OiJhdG9tIjtzOjIzOiIvc2NpLzI5Ny81NTg1LzEyNzcuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9 [7]: #xref-ref-2-1 View reference 2 in text [8]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BVirology%26rft.stitle%253DJ.%2BVirol.%26rft.issn%253D0022-538X%26rft.aulast%253DBarnett%26rft.auinit1%253DS.%2BW.%26rft.volume%253D75%26rft.issue%253D12%26rft.spage%253D5526%26rft.epage%253D5540%26rft.atitle%253DThe%2BAbility%2Bof%2Ban%2BOligomeric%2BHuman%2BImmunodeficiency%2BVirus%2BType%2B1%2B%2528HIV-1%2529%2BEnvelope%2BAntigen%2BTo%2BElicit%2BNeutralizing%2BAntibodies%2Bagainst%2BPrimary%2BHIV-1%2BIsolates%2BIs%2BImproved%2Bfollowing%2BPartial%2BDeletion%2Bof%2Bthe%2BSecond%2BHypervariable%2BRegion%26rft_id%253Dinfo%253Adoi%252F10.1128%252FJVI.75.12.5526-5540.2001%26rft_id%253Dinfo%253Apmid%252F11356960%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoianZpIjtzOjU6InJlc2lkIjtzOjEwOiI3NS8xMi81NTI2IjtzOjQ6ImF0b20iO3M6MjM6Ii9zY2kvMjk3LzU1ODUvMTI3Ny5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30= [10]: /lookup/doi/10.1126/science.291.5509.1686
Read full abstract