Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry.

Abstract

The worldwide effort to produce a vaccine against AIDS continues to disregard the fact that even human immunodeficiency virus (HIV)-specific neutralizing antibodies and cell-mediated immunity are ineffective against virus within cells without viral antigens on the cell membrane--and that much of HIV infection is transmitted in this manner. According to a recent report, a simian immunodeficiency virus vaccine that protected monkeys against an intravenous challenge with cell-free virus was, as predicted, ineffective against an intravenous challenge with the same amount of virus in infected cells. Moreover, antibody and HIV have been found to coexist in cell-free plasma from asymptomatic and symptomatic patients. Excluding direct introduction of HIV into the blood-stream, the most common and efficient form of transmission of HIV infection is by receptive anal intercourse, and semen contains large numbers of infected cells per milliliter. Recent reports showing that colorectal cells can be persistently infected by HIV and that HIV RNA and cDNA are present in the cells of the colon of dead AIDS patients indicate that either cell-free or intracellular HIV has the capacity to multiply at the portal of entry in the colorectal area without interference from neutralizing antibodies. The available data provide no basis for testing any HIV vaccine in human beings either before or after infection. The main challenge is to find a way to kill cells with chromosomally integrated HIV cDNA without harming normal cells, perhaps by identifying repressor proteins that might be produced by the cells with integrated HIV cDNA and thus could become specific targets for cell-killing drugs.

Antibodies protect mice against challenge with tick-borne encephalitis virus (TBEV)-infected macrophages

“…Indeed, the probability has been questioned for HIV [8], and results from SIV infection of macaques have shown that in this model it is not [7]. Recent work has suggested that natural TBEV infection via tick bite leads to viraemia by means of infected cells rather than free virus particles [6].…”

“…With tick-transmitted TBEV infection being introduced into the circulation by TBEV-infected cells rather than free virus particles, the meaning of results obtained by experimental syringe inoculation of free virus in relation to natural infection may be questioned. This even more so, as experiments on antibody-mediated protection, known to be effective against syringe inoculation of simian immunodeficiency virus (SIV) into macaques, could not be reproduced when virusinfected cells were applied for challenge [7], and the possibilities of antibodies being able to protect against virus challenge when contracted in the form of infected cells in general was questioned [8]. In the current study we investigated the capacity of TBEV antibodies to protect mice from challenge with TBEV-infected cells.…”

M Cells as Portals of Entry for HIV

“…Efforts to produce experimental anti-HIV vaccines often fail to consider that HIV may enter the body carried within cells as well as in a cell-free state [24]. With the introduction of semen large numbers of lymphocytes are also brought into contact with the rectal mucosa.…”

Trojan Horse macrophages: studies with the murine lactate dehydrogenase-elevating virus and implications for sexually transmitted virus infection

“…When the virus is sequestered in the form of virus-infected cells, viruses may be able to avoid internal lines of defence, leading to the potential for virus-infected cells to spread infection (Levy, 1988;Sabin, 1991Sabin, , 1992. Few if any studies are available which directly address the problem of whether virus-infected ceils are efficient vehicles for infection delivery.…”

“…LDV transmission has implications for the study of sexually transmitted disease as well as vaccination against sexually transmitted viruses which may travel in cells (Levy, 1988;Sabin, 1991Sabin, , 1992 …”