Robust vaccine-elicited cellular immune responses in breast milk following systemic simian immunodeficiency virus DNA prime and live virus vector boost vaccination of lactating rhesus monkeys.

Breast milk transmission of HIV remains an important mode of infant HIV acquisition. Enhancement of mucosal HIV-specific immune responses in milk of HIV-infected mothers through vaccination may reduce milk virus load or protect against virus transmission in the infant gastrointestinal tract. However, the ability of HIV/SIV strategies to induce virus-specific immune responses in milk has not been studied.

Clonal repertoires of virus-specific CD8+ T lymphocytes are shared in mucosal and systemic compartments during chronic simian immunodeficiency virus infection in rhesus monkeys.

Because it is thought that mucosal tissues play a fundamental role in early HIV/SIV infection, it is crucial to understand the virus-specific responses in mucosal tissues to facilitate devising strategies to prevent and control these infections. We have employed TCR repertoire analyses to define the clonal composition of a dominant SIV epitope-specific CD8(+) T cell population in mucosal and systemic compartments of SIV-infected rhesus monkeys during both acute and chronic infection. We show that the CD8(+) T cell repertoire in mucosal tissues of uninfected rhesus monkeys is oligoclonal, whereas the CD8(+) T cell repertoire in blood is polyclonal.

A matter of timing: unsynchronized antigen expression and antigen presentation diminish secondary T cell responses.

Despite the low and short expression of secondary Ag, prime-boost immunizations using homologous or heterologous vectors are capable of amplifying memory CD8(+) T cells. This is mainly attributed to the rapid presentation of Ag by APCs and the high proliferative capacity of memory CD8(+) T cells. Nevertheless, certain viruses and vectors often require prolonged Ag presentation for optimal T cell priming, and the influence of such a prolonged presentation during secondary immune induction is not clear.

Duration of antigen expression in vivo following DNA immunization modifies the magnitude, contraction, and secondary responses of CD8+ T lymphocytes.

The duration of Ag expression in vivo has been reported to have a minimal impact on both the magnitude and kinetics of contraction of a pathogen-induced CD8(+) T cell response. In this study, we controlled the duration of Ag expression by excising the ear pinnae following intradermal ear pinnae DNA immunization. This resulted in decreased magnitude, accelerated contraction and differentiation, and surprisingly greater secondary CD8(+) T cell responses.

An alternate mechanism of abortive release marked by the formation of very long abortive transcripts.

The Esigma70-dependent N25 promoter is rate-limited at promoter escape. Here, RNA polymerase repeatedly initiates and aborts transcription, giving rise to a ladder of short RNAs 2-11 nucleotides long. Certain mutations in the initial transcribed sequence (ITS) of N25 lengthen the abortive initiation program, resulting in the release of very long abortive transcripts (VLATs) 16-19 nucleotides long.