Effect Of Therapeutic Hiv Vaccine On Cd4 Count And Viral Load Of Aids Patients: Hope For Care Of Hiv Infections.
E Okwori. Effect Of Therapeutic Hiv Vaccine On Cd4 Count And Viral Load Of Aids Patients: Hope For Care Of Hiv Infections.. The Internet Journal of Infectious Diseases. 2009 Volume 9 Number 1.
Previous efforts by great scientists were made to develop HIV vaccine using genetic engineering. There was no much success achieved. At our end live attenuated, killed or fragments of the virus was used as a vaccine. The vaccine was first produced in 1987 and used on thirty five (35) AIDS patients. The patients were monitored and followed up, using CD4 count, viral load and clinical parameters. Based on the above thirty five of them responded positively to the therapy. The result of this study had given hope for cure of HIV infection.
Since 1984, when DR Robert Gallo declared at the American national cancer institute (ANCL), the discovery of Human immune deficiency virus (HIV), the virus that cause Acquire immune deficiency syndrome (AIDS), the human existence has been attacked by the deadly diseases, with devastating effect (1,2,3). Report have it that as of 1998 AIDS has killed no fewer that 14 million people worldwide and over 40 million people were living with HIV. About seventy-five (75) percent of the people were living in the developing countries. The picture presently is gloomier in Africa where AIDS kills about 5, 000, and infects 11,000 every day ( 3,4,5).At present almost every family seams to be affected. It is believed that AIDS has killed more people than those killed in the wars of Africa combined (5). Cases of HIV/AIDS have now been reported in virtually all ages and every tribe and both sexes. Surveillance reports have shown that the rate of infection in Nigeria is spreading like wild fire (6). For instance the prevalence of the disease was 1.4% in 1992, rose to 3.8% in 1994. In 1997 4.1% of the adults in Nigeria were infected (4, 5, 6). According to United Nations program on AIDS report of 1998 approximately 590,000 Nigeria developed full blown AIDS by the end of 1997 (5). It was reported that more than 2.2 million Nigerians were infected with HIV in 1998 (5).
In Nigeria and other developing countries where most of the HIV infected people reside, the vast majority of them could not afford anti retroviral drugs by the time of this research (1997-1998) there was accordingly, a growing census that the development of a safe, effective and cheap vaccine against HIV represents the world’s most urgent public priority.
Unfortunately, it was taking much longer to develop such a vaccine than was anticipated back in 1983-84, when research on HIV began in earnest. The reasons for this may be as a result of the tremendous degree of anti-genic variability seen among different clinical isolates and subtypes of HIV. Another reason is the particular route of transmission used by HIV which will probably require that a vaccine elicit both mucosal and systemic immunity. It is against this background however that I developed this classical approach of using mainly the whole virus /life attenuated or killed vaccine, to stimulate specific anti-HIV cellular and humoral immune response. Attenuated vaccines have been widely used around the world to protect against other viral diseases, including rabies, small pox, polio, yellow fever, measles and mumps. In each case the immunity from the poorly replicating virus (vaccine) strains is able to clear the attenuated virus, the virus and to provide long-lasting immunity against re-infection by the same pathogen. However before this research there were no attenuated vaccines in use against disease caused by HIV. To use a vaccine as preventive one must be sure that it is avirulent. This concern is highlighted by findings that vaccinated newborn macaques with strains of SIV (Simian immune deficiency Virus) caused fatal immune disease (6,7). No one should try to down play either this problem or the fact that an attenuated HIV vaccine strains may be spread to the partners and vaccinated women to their babies.
It would be wrong to argue that the development of live attenuated HIV vaccine is not associated with biological and ethical problem. That is the reason for using the vaccine only on AIDS patients. On the other hand, would it be ethical to stop or delay research into such a product if other approaches fail and we then have a world with more than one hundred million people infected with HIV.
Nigerians are so highly infected with the virus that it is now difficult to say whether the so-called normal people moving around are HIV free. It is against this background that I developed this safe HIV therapeutic vaccine the use is strictly on people living with AIDS(PLWA).
HIV THERAPEAUTIC VACCINE PATIENTS AND THE METHODOLOGY
Based on their clinical and laboratory status and for the purpose of this therapy, the patients were classified I.i.e clinical and pathological.
HIV Positive patient with count between 200-299 cells/UL
HIV positive patient with Cd4 count between 100-199 cells/ UL
HIV positive patients with CD$ count between 0-99 cells /UL
These classifications emanated from experience gathered in the course of handling the patients; and is useful in monitoring them.
VACCINE PRODUCTION AND REGIME OF ADMINISTRATION.
The virus is obtained form the patient’s blood and turned into vaccine, using heat method. There are two methods in performing the vaccine.
High temperature-short time method (HT-LT) 65 C for 10 minute.
Low temperature- long time method (LT-LT) 45 C for 24 hours.
The choice of the method depends on the number of patients recruited at a particular period, on the work –load and also depends on the urgency of requirement of the vaccine. But the one prepared under low temperature, longtime was more potent and acts for a longer period, based on the immunological response as determined by CD4 count monitoring.
The amount of blood collected from each patient is abut 20mls, centrifuged at 1000 Rev. per minute for ten minutes to obtain serum from the blood. The serum is believed to certain the virus.
This study was carried out at general Hospital Otukpo, Benue State of Nigeria.
The patient were Categorized into three main groups, A, B, & C based on their clinical presentation and their CD4+ cell count.
Thirty five of the patients could afford the Laboratory test CD4 cell count and viral load and were fallowed up with such tests.
There was correlation of their clinical staff with the pathological staffing of thirty of their patents.
In average, Their was a lot of their virus load between 380 to 2000 in two month, and increase in their CD4 count between150 to 2200 cell, during the same period.
In the third month of between 100-200 was generally fall in CD4 count, and a rise in between 230-360 their viral load in thirty four of the patent who used anti-retroviral doses with the vaccine maintained length CD4 count 740,27+0 load viral load (2300 copies/UL).
The C D4 count picked up by 100 to 370 cells /UL in all of them, and a slight fall in the sixth month; with a fall of viral load by 160-1500 copies /UL in all.
The vaccine had to be repeated every three months to maintain high CD4 count and low viral load.
Thirty five patents who were neither on the vaccine or counterfeiter viral doses were monitored clerically. Thirty three of them died within one year. The other two started the antiretroviral dry thereafter.
VIRAL LOAD OF THE PATIENT ON THE THERAPITIC VACCINE.
PERIOD IN MONTHS
A lot of work earlier done on the nature of the agent (HIV causing the deadly disease (AIDS) by Gallo & Border in USA. It is also interesting to note that efforts were being made to establish the prevalence of the disease world – wide.
Anti retroviral drug were also discovered to have some significant effects on the virus, thereby prolonging the life span of the HIV infected individuals using the drugs. Some efforts were also made to develop preventive vaccines against the agents.
At our end here I have locally developed a vaccine against HIV infection based on the following principles:-
(A) The virus has a long incubation period (about 3 – 10 years) so the vaccine mount a lot of immune system, both humored and cell medicated before the disease (AIDS) is produced.
(B) The cell mainly attacked by virus in human are mainly the T4 (helper) lymphocytes which are the coordinating cell in the immune response. It is worth noting that the cell (T4 or helper) are labile cells, that is, they have a surviving period in the blood, whether infected or free, and after which they are dead and are replaced by new ones.
(C) There is presently no evidence that the virus can replicate in the stem cells.
Based on the above, total eradication of the virus from the cells and the plasma amounts to cure. The only effective way of doing that is by immune system, both cells mediated and humored.
The TC (cytotoxic cell) kills the intra cellular viruses, while the antibodies clear the free viruses in the circulation.
MECHANISM OF ACTION OF THE VACCINE:-
Cell Mediated cytotoxicity:
Cell mediated immunity is mounted against the vaccine which is an antigen to the body. The same immunity is extended to the intra – cellular viruses (HIV) with the same epitone.
Three distinct phases have been described in the cell mediated cytotoxity:-
(1) Binding to target (2) rearrangement of cytoplasmic granules and the release of their content and (3) target cell (HIV) death.
Once the effectors – target conjugate is the cytoplasmic granules appear to become rearranged and concentrated at the side of the cell adjacent to the target. The granule content are then released into the space between the two cells.
There are at least three different types of molecules stored within the granule that can cause cell death. T-cell contains perforin. In the presence of Ca 2+ ions the perforin binds to the membrane and polymerizes to form a transmembrane pore. This upsets the osmotic balance of the virus and leads to its death.
Once the effectors – target conjugate is formed the cytoplasmic granule appears to become rearrange and concentrated at the side of the cell adjacent to the target. The granule contents are then released into the space between the two cells.
There are at least three different types of molecules stored within the granules thet can cause cell death. T-cell contain perforin. In the presence of Ca 2= ions the perforin binds to the membrane and polymerizes to form a transmembrane pore. This upset the osmotic balance of the virus and leads to its death. The granules also contain at least two serine esterases that may play a role in destroying the viruses. Cytotoxic cells also produce a number of other toxic molecules, including tumor necrosis factor (TNF+), lymphotoxin (TNFB) Y-interferon. The process is unidirectional with only the target cell being destroyed. The cell can then move on and eliminate other viruses.
The other arm of the cell mediated immunity is dependent on the production of lymphokins from antigen- activated T – lymphocytes. These molecules produced in an antigen specific fashion can act in an antigen non-specific manner to recruit, activation and regulate effectors cells with the potential to combat the HIV.
The first cells be activated are CD4+ T cells that recognize the virus in association with MHC complex, and produce a variety of lymphokins that act on B cells.
The HIV- stimulated B cell develop under the influence of the interleukins -4 that is produced by closely adherent T cells. The interleukins -5 and interleukins -6 then bring the B cells to state of full activation with terminal differentiation into an immunoglobin producing plasma cells.
Therefore, for both Band T cells activation two stimuli are required. The recognition of the virus makes sure that only those cells that will be effective against the viral material are recruited. The co-stimulatory signal has evolved control the process and aid discrimination of self and non-self.
The HIV- antibody complex takes place and the complex from the circulation by excretion and the phagocyic cells.
DEFINATION OF CURE
Cure means fulfillment of any of the criteria stated below by any of the patients
1. Persistent nil virus in the circulation for up to one year after discontinuation of the vaccine
2. Peresistent normal CD4 cells for up to one year after discontinuation of the vaccine.
3. Patient remains clinically free from the presenting features for one year after strapping the vaccine.
There was generally a rise in the CD4x cells after the vaccine in the second month for all the patients example, the CD4X cell count of patient 698AA rose from the baseline of 370 cells/ul to 2570 cells/ul in the second month.
There was a slight drop of the CD4X cell count of the patients in the third month, an average drop of 121 cells. It may be that the effect of the vaccine reduced at three months, and the stimulated CD4 cells started dropping.
Given the booster dose of the vaccine the CD4 rose very well, for example the mean CD4X cell count for the patients was 843 cell/ul after one year. A corresponding reduction in the viral load after the vaccine was discovered. The mean baseline viral load of the patients was 1209888 copes/ul, which reduced to 33,957 copes/ul in the twelfth month. That is a clear indication that the vaccine was effective. The viral load of four patients was not available (NA) from the third month. That might be due to financial constraint, but they were able to do the CD4X cell count.The viral load of ten of the patients could no be detected in their blood at one year.That collaborated the effectiveness of the vaccine of being capable of eliminating the virus from the blood of the infected persons.
Thirty five patients who received the vaccine were followed-up and monitored
1. All the patients had their CD4 cell rose above normal after receiving the vaccine. That was as a result of stimulation of the immune system by the vaccine
2. There was a corresponding reduction of the viral load of the patients.
3. That the vaccine is capable of clearing the viruses from circulation and improve the immune status of the patients.
THE FUTURE PROSPECT OF THE THERAPHY.
The positive result of this study has opened another chapter and hope in the treatment and control of HIV/AIDS.
Preparation of vaccine targeted at the HIV incorporated into the host DNA is the next step, which may be capable of cure of the disease.
An appeal is hereby made to the federal government, to set up Retroviralogy research centre with a view of further indepth study into this deadly disease. At this centre, pure HIV vaccines will be produced.
Production of pure vaccine will help many patients, both in the urban and rural areas.
My gratitude to the Almighty God who gave me the knowledge of this work.
I am grateful to our Lord Jesus who through the immaculate heart of our Blessed Mother, Virgin Mary blessed this project.
I am thankful to professor C. Wambebe and the staff of NIPRD who collaborated with me in this project.