Performance of commercially available HIV Rapid and HIV ELISA
test kits on post HIV vaccination samples to evaluate Vaccine
Induced Sero-Reactivity
1,
1
Stevens , Bashir
2
Farah ,
2
Mwangi ,
2
Wangui ,
1
Schmidt ,
1
Laufer ,
2
Anzala
Paramesh Chetty Gwynn
Irene
Stella
Claudia
Dagna
Omu
1 International AIDS Vaccine Initiative (IAVI), New York, USA and 2 Kenyan AIDS Vaccine Initiative (KAVI), Nairobi Kenya
BACKGROUND
METHODS
RESULTS
Phase 1 preventative HIV vaccine clinical trials enrol low risk HIV negative volunteers. Most HIV
vaccine immunogenes encode proteins mainly from the env, gag, pol, and nef regions and are
designed to induce the production of protective antibodies. The elicited vaccine induced
After un-blinding 31/32 of the vaccine recipients were shown to express VISR. The 31 volunteers that received
Table 1: KAVI Section of Study Design
Group
Vaccines
Dose
test kits’ results. Delineation of these seropositive results among vaccine recipients has resulted
F
crucial in distinguishing VISP from true HIV infection.
Month 0
Month 3
Month 6
Table 4. Comparison of test kit Results
placebo)
E
RNA detection. Determining the best suited HIV testing algorithm for a particular product/trial is
(active/
G
H
Ad26.ENVA.01,
Ad35-ENV
5x1010 vp/
5x1010 vp
Ad35-ENV,
Ad26.ENVA.01
5x1010 vp/
5x1010 vp
Ad26.ENVA.01,
Ad26.ENVA.01
5x1010 vp/
5x1010 vp
Ad35-ENV, Ad35ENV
5x1010 vp/
5x1010 vp
10
Ad26
Ad35
-
Ad35
Ad26
-
Ad26
Ad26
-
Ad35
Ad35
-
(8/2)
10
(8/2)
10
(8/2)
10
(8/2)
40
Total
32/8
Table 2: Vaccination visits and HIV
testing time points
METHODS
HIV-uninfected study volunteers were randomised to receive either the Ad26-ENVA or Ad35-ENV
Ad35-ENV: Recombinant adenovirus serotype 35
vector vaccine is a recombinant replicationincompetent product that encodes the HIV-1 subtype
Agp140 env gene. (Figure 1)
Ad26.ENV.01 (rAd26): Recombinant adenovirus
serotype 26 vector vaccine is a recombinant
replication-deficient product composed of an
adenovirus serotype 26 vector that encodes the HIV-1
Clade A Env glycoprotein 140 (strain 92rw020)(Figure 1).
product, or both products or placebo in a prime-boost regimen as in Table 1.
Samples stored from 32 vaccine and 8 placebo recipients at 2 months and 9 months post last
the investigational product and expressed VISR had HIV-1 RNA PCR confirmatory tests conducted and all test
results were undetectable for HIV-1 wild type infection.
N
antibodies (VISP) in the absence of HIV infection can confound the interpretation of standard HIV
in the use of more complicated HIV testing algorithms and laboratory techniques, such as HIV-1
Figure 1: Vaccine Inserts
Vaccine recipients showed higher percentages of reactive results using the 4th generation (BioMerieux
Vironostika Ag/Ab and Mini-Vidas Ultra Duo Ag/Ab, 96.9%) versus 3rd generation (Alere Determine HIV 1/2,
Table 3: Details of Kit Inserts
vaccination were tested on 4 different HIV test kits at the KAVI research centre in Nairobi, Kenya. Details
Figure 2: On study HIV testing Algorithm
37.5% & 9.4%; Trinity Uni-Gold HIV, 50% & 3.1%) HIV test kits (Table 4).
No placebo recipients showed any VISR.
of the test kits can be found in Table 3.
VISR declined over time, possibly due to waning of the vaccine induced antibody titre.
Samples from 2 months and 9 months post last vaccination visits were tested using the HIV Rapid test
kits (Alere Determine HIV-1/2 and Trinity Uni-Gold HIV) and BioMerieux Vironostika HIV Ag/Ab Elisa kits.
.
CONCLUSION
Samples only from 9 months post last vaccination were tested on the HIV ELISA Mini-Vidas HIV Duo
Ultra (HIV5) Ag/Ab test kit and. Data for 2 months post last vaccination were already available for the
Selection of appropriate HIV test kits when developing a suitable HIV testing algorithm(s) to support a
Vironostika HIV Ag/Ab test kit as part of the on study HIV testing algorithm.
preventative HIV vaccine trial can be challenging. 3rd generation HIV Rapid test kits were much less
sensitive, detecting VISR less often when compared to 4th Generation ELISA kits. Post vaccination
*Only available information from package insert
for Alere Determine HIV-1/2 is the sensitivity
Profile as listed below:
HIV-1 Positive 100%
HIV-2 Positive 100%
HIV-1 Subtype A-G 100%
HIV-1 Group O 100%
samples from previous HIV vaccine trials with similar products are useful when designing HIV testing
algorithms for subsequent trials.
The occurrence of VISR is dependent on the HIV gene inserts in both the test kit and the investigational
product.
The above analysis indicated that HIV vaccines that carry the ENV gene tend to trigger VISR,
particularly when using a 4th generation HIV ELISA test kit.
Optimally an HIV testing algorithm would include HIV test kits that only detect HIV-1 wild type infection
Kanya AIDS Vaccine Initiative (KAVI)
Clinical Team
KAVI Laboratory Team
(Left to right) I. Mwangi. B. Farah, S.Ogola,
R. Chirchir And R. Langat
REFERENCES
1
2
Etienne Karita et al., Safety in a
Phase 1 randomized, doubleblind, placebo-controlled trial
evaluating two adenovirus HIV
vaccines in three different
geographic regions (IAVIB003/IPCAVD-004/HVTN091
trial)
Jill Gilmour et al.,
Immunogenicity of homologous
and heterologous regimens of
Ad26-EnvA.01 and Ad35EnvA HIV vaccines in HIVuninfected volunteers in the US
and Africa
and not VISR in a cost effective, timely manner to mitigate anxiety and potential social harm to the
volunteer. In Kenya / Africa setting community based HIV testing is done using the HIV Rapid tests.
Collecting post-trial follow-up data on VISR is important to better characterize VISR persistence and to
avoid potential VISR results through community-based HIV testing of volunteers.
ACKNOWLEDGEMENTS
Thanks to all the dedicated trial participants, the staff at the clinical sites and immunology support laboratories.
Thanks to EMMES and SCHARP for data analysis and clinical trial database support.
The B003/IPCAVD004/HVTN091 clinical trial was conducted at the Brigham and Women's Hospital, Harvard Medical
School, USA; Projet San Francisco, Rwanda; Zambia HIV Research Group, Zambia; Kenya AIDS Vaccine Initiative,
Kenya; The Desmond Tutu HIV Centre Institute of Infectious Disease and Molecular Medicine Faculty of Health
Sciences, South Africa; Perinatal HIV Research Unit, South Africa; The Aurum Institute for Health Research, South
Africa; in collaboration with the Beth Israel Deaconess Medical Center, Harvard Medical School, USA; the Fred
Hutchinson Cancer Research Center, USA; the HIV Vaccine Trial Network, USA; The Ragon Institute, USA; the
National Institute of Allergy and Infectious Diseases, USA and Crucell Holland BV, Netherland.